Oxidative DNA damage during night shift work.

PubMed

Bhatti, Parveen; Mirick, Dana K; Randolph, Timothy W; Gong, Jicheng; Buchanan, Diana Taibi; Zhang, Junfeng Jim; Davis, Scott

2017-09-01

We previously reported that compared with night sleep, day sleep among shift workers was associated with reduced urinary excretion of 8-hydroxydeoxyguanosine (8-OH-dG), potentially reflecting a reduced ability to repair 8-OH-dG lesions in DNA. We identified the absence of melatonin during day sleep as the likely causative factor. We now investigate whether night work is also associated with reduced urinary excretion of 8-OH-dG. For this cross-sectional study, 50 shift workers with the largest negative differences in night work versus night sleep circulating melatonin levels (measured as 6-sulfatoxymelatonin in urine) were selected from among the 223 shift workers included in our previous study. 8-OH-dG concentrations were measured in stored urine samples using high performance liquid chromatography with electrochemical detection. Mixed effects models were used to compare night work versus night sleep 8-OH-dG levels. Circulating melatonin levels during night work (mean=17.1 ng/mg creatinine/mg creatinine) were much lower than during night sleep (mean=51.7 ng/mg creatinine). In adjusted analyses, average urinary 8-OH-dG levels during the night work period were only 20% of those observed during the night sleep period (95% CI 10% to 30%; p<0.001). This study suggests that night work, relative to night sleep, is associated with reduced repair of 8-OH-dG lesions in DNA and that the effect is likely driven by melatonin suppression occurring during night work relative to night sleep. If confirmed, future studies should evaluate melatonin supplementation as a means to restore oxidative DNA damage repair capacity among shift workers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Trace elements are associated with urinary 8-hydroxy-2'-deoxyguanosine level: a case study of college students in Guangzhou, China.

PubMed

Lu, Shaoyou; Ren, Lu; Fang, Jianzhang; Ji, Jiajia; Liu, Guihua; Zhang, Jianqing; Zhang, Huimin; Luo, Ruorong; Lin, Kai; Fan, Ruifang

2016-05-01

Many trace heavy elements are carcinogenic and increase the incidence of cancer. However, a comprehensive study of the correlation between multiple trace elements and DNA oxidative damage is still lacking. The aim of this study is to investigate the relationships between the body burden of multiple trace elements and DNA oxidative stress in college students in Guangzhou, China. Seventeen trace elements in urine samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative stress, was also measured using liquid chromatography tandem mass spectrometer (LC-MS/MS). The concentrations of six essential elements including manganese (Mn), copper (Cu), nickel (Ni), selenium (Se), strontium (Sr), and molybdenum (Mo), and five non-essential elements including arsenic (As), cadmium (Cd), aluminum (Al), stibium (Sb), and thallium (Tl), were found to be significantly correlated with urinary 8-OHdG levels. Moreover, urinary levels of Ni, Se, Mo, As, Sr, and Tl were strongly significantly correlated with 8-OHdG (P < 0.01) concentration. Environmental exposure and dietary intake of these trace elements may play important roles in DNA oxidative damage in the population of Guangzhou, China.

Urinary Concentrations of Phthalates in Couples Planning Pregnancy and Its Association with 8-Hydroxy-2′-deoxyguanosine, a Biomarker of Oxidative Stress: Longitudinal Investigation of Fertility and the Environment Study

PubMed Central

2015-01-01

Oxidative stress has been recognized as one of the most important contributors to infertility in both males and females. Exposure to many environmental chemicals, such as phthalates, has been shown to induce oxidative stress. In a longitudinal study designed to assess exposure to environmental chemicals and fecundity in couples who were planning pregnancy, 894 urine samples were collected from 469 couples from Michigan and Texas during 2005–2009. The concentrations of 14 phthalate metabolites and a marker of oxidative stress, 8-hydroxy-2′-deoxyguanosine (8-OHdG), were determined in these samples. Concentrations, profiles, and estimated daily intakes (DIs) of phthalates were positively associated with 8-OHdG. The median concentrations of monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono(3-carboxypropyl) phthalate (mCPP), mono-n-butyl phthalate (mBP), mono(2-isobutyl) phthalate (miBP), monobenzyl phthalate (mBzP), Σ5mEHP (sum of five metabolites of di(2-ethylhexyl) phthalate (DEHP)) and Σ14phthalates (sum of 14 urinary phthalate metabolites) were 0.48, 85.2, 4.50, 7.66, 4.36, 3.80, 54.8, and 249 μg/g creatinine, respectively. The estimated DI values for DEHP in 39 individuals were above the U.S. Environmental Protection Agency’s (EPA) reference dose (RfD) of 20 μg/kg-bw/day. The mean and median concentrations of 8-OHdG were 6.02 and 3.13 μg/g creatinine, respectively, which were significantly higher in females than in males. Statistically significant associations were found between 8-OHdG and urinary concentrations of mEP, and Σ5mEHP for females. Similarly, a significant association was found between 8-OHdG and DIs estimated for select phthalates. Our results suggested that phthalate exposure increases oxidative stress, which can be a mechanism for the diminished fertility observed in couples who were highly exposed to select phthalates. PMID:25068827

The Omega-3 Index Is Inversely Associated with Depressive Symptoms among Individuals with Elevated Oxidative Stress Biomarkers123

PubMed Central

Bigornia, Sherman J; Falcón, Luis M; Ordovás, José M; Lai, Chao-Qiang

2016-01-01

Background: Omega-3 (n–3) fatty acid (FA) consumption is thought to improve depressive symptoms. However, current evidence is limited, and whether this association exists among Puerto Ricans, a population burdened by depression, remains uncertain. Objectives: We examined the association between ω-3 FA biomarkers and depressive symptoms as well as the potential influence of oxidative stress. Methods: Baseline and longitudinal analyses were conducted in the Boston Puerto Rican Health Study (n = 787; participants aged 57 ± 0.52 y, 73% women). Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentration, a measure of oxidative stress, and erythrocyte FA composition were collected at baseline. We calculated the omega-3 index as the sum of eicosapentaenoic and docosahexaenoic acids, expressed as a percentage of total FAs. Baseline and 2-y depressive symptoms were characterized by using the Center for Epidemiological Studies–Depression Scale (CES-D). Statistical analyses included linear and logistic regression. Results: Urinary 8-OHdG concentration tended to modify the relation between the erythrocyte omega-3 index and baseline CES-D score (P-interaction = 0.10). In stratified analyses, the omega-3 index was inversely associated with CES-D score (β = −1.74, SE = 0.88; P = 0.02) among those in the top quartile of 8-OHdG concentration but not among those in the lower quartiles. The relation between the omega-3 index and CES-D at 2 y was more clearly modified by 8-OHdG concentration (P-interaction = 0.04), where the omega-3 index was inversely associated with CES-D at 2 y, adjusted for baseline (β = −1.66, SE = 0.66; P = 0.02), only among those with elevated 8-OHdG concentrations. Among individuals not taking antidepressant medications and in the top tertile of urinary 8-OHdG concentration, the omega-3 index was associated with significantly lower odds of a CES-D score ≥16 at baseline (OR: 0.72; 95% CI: 0.53, 0.96) but not at 2 y (OR: 0.83; 95% CI: 0.60, 1.15). Conclusions: An inverse association between the omega-3 index and depressive symptoms was observed among participants with elevated oxidative stress biomarkers. These data suggest that oxidative stress status may identify those who might benefit from ω-3 FA consumption to improve depressive symptoms. PMID:26936135

Relationship between bisphenol A exposure and attention-deficit/ hyperactivity disorder: A case-control study for primary school children in Guangzhou, China.

PubMed

Li, Yanru; Zhang, Haibin; Kuang, Hongxuan; Fan, Ruifang; Cha, Caihui; Li, Guanyong; Luo, Zhiwei; Pang, Qihua

2018-04-01

Bisphenol A (BPA) is an endocrine-disrupting chemical. Studies have shown that the exposure to BPA is associated with attention-deficit/hyperactivity disorder (ADHD) during adolescent development. However the direct clinical evidence is limited. To investigate the possible association between environmental BPA exposure and the altered behavior of children, a case-control study was conducted with children aged 6-12 years in Guangzhou, China. Two hundred fifteen children diagnosed with ADHD and 253 healthy children from Guangzhou were recruited as the case and control groups, respectively. Urinary BPA and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage) concentrations were determined by high-performance liquid chromatography/tandem spectrometry. The results showed that concentrations of urinary BPA for the case group were significantly higher than those for the control group (3.44 vs 1.70 μg/L; 4.63 vs 1.71 μg/g Crt. p < .001). A stepwise increase in the odds ratios for ADHD was observed with the increasing quartiles of children's urinary BPA (first quartile: reference category; second quartile adjusted OR: 1.79, 95% CI: 0.95-3.37; third quartile adjusted OR: 7.44, 95% CI: 3.91-14.1; fourth quartile adjusted OR: 9.41, 95% CI: 4.91-18.1). When the BPA levels were stratified by gender, the odds of ADHD among boys and girls increased significantly with urinary BPA concentrations (adjusted OR: 4.58, 95% CI: 2.84-7.37; adjusted OR: 2.83, 95% CI: 1.17-6.84). Urinary 8-OHdG concentrations in the ADHD children were significantly higher than those in the control group. Furthermore, the linear regression analysis results indicated that a significant relationship existed between BPA exposure and 8-OHdG levels (R = 0.257, p < .001). Our findings provide direct evidence that childhood BPA exposure may be related to ADHD and 8-OHdG concentrations for children. Moreover, BPA exposure could increase the higher occurrence of ADHD for boy than for girls. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urinary level of nickel and acute leukaemia in Chinese children.

PubMed

Yang, Y; Jin, X M; Yan, C H; Tian, Y; Tang, J Y; Shen, X M

2008-10-01

The 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage but might also be a risk factor for many diseases including cancer. Metal exposure may play an important role in oxidative DNA damage among children. However, few studies on urinary 8-OHdG and metals have been conducted in children with acute leukemia. In the present study, urinary Ni and 8-OHdG were examined in 116 children with acute leukaemia (94 acute lymphoid leukaemia [ALL] and 22 acute myeloid leukaemia [AML]) and 51 healthy child controls. Our result showed that urinary Ni in acute leukaemia patients (ALL: 68.40 +/- 133.98, AML: 41.48 +/- 76.31 ng/mg creatinine) was significantly higher than that in controls (62.47 +/- 124.90 vs 17.63 +/- 46.17 ng/mg creatinine, P < 0.05). Similarly, the pretherapy level of urinary 8-OHdG in patients (ALL: 11.83 +/- 16.23, AML: 12.36 +/- 11.36 ng/mg creatinine) was significantly elevated compared with controls (11.92 +/- 15.42 vs 4.03 +/- 4.70 ng/mg creatinine, P < 0.05). Moreover, urinary 8-OHdG and urinary Ni showed a weak but significant association with increased risk of childhood leukaemia. The present study suggests that Ni may be an etiologic factor for childhood acute leukaemia by oxidative DNA damage.

Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2′-deoxyguanosine by UPLC-MS/MS Analysis

PubMed Central

Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

2016-01-01

Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7−5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC. PMID:27585556

Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2‧-deoxyguanosine by UPLC-MS/MS Analysis

NASA Astrophysics Data System (ADS)

Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

2016-09-01

Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2‧-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7-5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC.

Urinary 1-hydroxypyrene and 8-hydroxydeoxyguanosine levels among coke-oven workers for 2 consecutive days.

PubMed

Nguyen, Thi-To-Uyen; Kawanami, Shoko; Kawai, Kazuaki; Kasai, Hiroshi; Li, Yun-Shan; Inoue, Jinro; Ngoan, Le Tran; Horie, Seichi

2014-01-01

This study evaluated the levels of exposure to polycyclic aromatic hydrocarbons (PAHs) and their relationship with oxidative DNA damage among Vietnamese coke-oven workers. We collected urine from 36 coke-oven workers (exposed group) at the beginning and end of the shift on 2 consecutive days. We also collected urine from 78 medical staff (control group). Information was collected by questionnaire about smoking status, drinking habit, and working position. Urinary 1-hydroxypyrene (1-OHP) and 8-hydroxydeoxyguanosine (8-OH-dG) were measured using HPLC. All statistical analyses were performed with SPSS version 19. Urinary 1-OHP was significantly higher in the coke-oven workers than in the control group (p<0.05). Top-oven workers had the highest levels of internal exposure to PAHs, followed by side-oven and then bottom-oven workers (5.41, 4.41 and 1.35 ng/mg creatinine, respectively, at the end of the shift on day 2). Urinary 8-OH-dG was significantly higher in top- and side-oven workers at the end of the shift on day 2 (4.63 and 5.88 ng/mg creatinine, respectively) than in the control group (3.85 ng/mg creatinine). Based on a multi-regression analysis, smoking status had a significant effect on urinary 8-OH-dG (p=0.049). Urinary 1-OHP tended to have a positive correlation with urinary 8-OH-dG (p=0.070). Vietnamese coke-oven workers were exposed to PAHs during their work shift. Urinary 1-OHP exceeded the recommended limit, and elevated oxidative DNA damage occurred in top- and side-oven workers on the second day of work. A tendency for positive correlation was found between urinary 1-OHP and urinary 8-OH-dG.

8-hydroxy-2'-deoxyguanosine (8-OHdG) biomarker detection down to picoMolar level on a plastic antibody film.

PubMed

Martins, Gabriela V; Marques, Ana C; Fortunato, Elvira; Sales, M Goreti F

2016-12-15

An innovative biosensor assembly relying on a simple and straightforward in-situ construction is presented to monitor urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) down to the pmol/L level. The sensing film of the biosensor consisted of a molecularly imprinted polymer (MIP) layer for 8-OHdG assembled on a gold electrode through electropolymerization of monomer combined with the template. The analytical features of the resulting biosensor were assessed by Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS). Some experimental parameters such as the initial concentration of the monomer and the ratio template-monomer were investigated and optimized in order to finely tune the performance of the MIP-based sensor. Under optimal conditions, the developed biosensor was able to rebind 8-OHdG with a linear response against EIS from 0.1 to 100pg/ml 3.5-3500 pM. The interference of coexisting species was tested, also with calibrations on urine samples, and good selectivity towards 8-OHdG was obtained. RAMAN spectroscopy, FTIR and SEM evaluations of the prepared films confirmed the formation of a polyphenol thin-film on the electrode surface. The presence and distribution of the imprinted cavities on the MIP layer was confirmed by confocal microscopy imaging of the film, after a post-treatment with Fluorescein Isothiocyanate (FITC) labeled 8-OHdG antibody. Overall, this label-free biosensor for urinary 8-OHdG detection constitutes a promising low-cost alternative to the conventional immunoassay approaches, due to its simplicity, stability, high sensitivity and selectivity for biological sample assays, opening new doors for other applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Environmental exposure to human carcinogens in teenagers and the association with DNA damage.

PubMed

Franken, Carmen; Koppen, Gudrun; Lambrechts, Nathalie; Govarts, Eva; Bruckers, Liesbeth; Den Hond, Elly; Loots, Ilse; Nelen, Vera; Sioen, Isabelle; Nawrot, Tim S; Baeyens, Willy; Van Larebeke, Nicolas; Boonen, Francis; Ooms, Daniëlla; Wevers, Mai; Jacobs, Griet; Covaci, Adrian; Schettgen, Thomas; Schoeters, Greet

2017-01-01

We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Six hundred 14-15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14-15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: application of salivary and urinary biomarkers.

PubMed

Hinhumpatch, Pantip; Navasumrit, Panida; Chaisatra, Krittinee; Promvijit, Jeerawan; Mahidol, Chulabhorn; Ruchirawat, Mathuros

2013-12-15

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r=0.56, P<0.001) and arsenic concentration in urine (r=0.50, P<0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (~4-fold, P<0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (~3-fold, P<0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. © 2013.

Evaluation of the oxidative deoxyribonucleic acid damage biomarker 8-hydroxy-2'-deoxyguanosine in the urine of leukemic children by micellar electrokinetic capillary chromatography.

PubMed

Zhang, Pingping; Lian, Kaoqi; Wu, Xiaoli; Yao, Min; Lu, Xin; Kang, Weijun; Jiang, Lingling

2014-04-04

Determining the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA damage biomarker, is vital to the study of clinical pathogenesis and drug toxicity. The principal limitation of capillary electrophoresis (CE) with UV detection is its low sensitivity. To overcome this shortcoming, we developed a micellar electrokinetic capillary chromatography (MEKC) with solid-phase extraction (SPE) for urinary 8-OHdG analysis. The sensitivity of MEKC-UV was improved using a reasonable UV system, injection mode, and SPE. The parameters affecting MEKC and SPE were also optimized. The calibration curve was linear within the range from 1 to 500 μg L(-1). The limits of detection and quantification were 0.27 μg L(-1) and 0.82 μg L(-1), respectively. Interday and intraday precision were both <5.6%. The recovery of 8-OHdG in urine ranged from 94.5% to 103.2%. This method was used to measure urinary 8-OHdG from eight normal children, eight newly diagnosed leukemic children, and eight leukemic children undergoing chemotherapy. The results show that the proposed method can be used to assess oxidative stress in patients and the side effects of chemotherapeutic drugs by measuring urinary 8-OHdG. Copyright © 2014 Elsevier B.V. All rights reserved.

Detection and Quantification of 8-Hydroxy-2′-Deoxyguanosine in Alzheimer’s Transgenic Mouse Urine using Capillary Electrophoresis

PubMed Central

Zhang, Cheng; Nestorova, Gergana; Rissman, Robert A.; Feng, June

2013-01-01

8-Hydroxy-2′-deoxyguanosine (8-OHdG) is one of the major forms of oxidative deoxyribonucleic acid (DNA) damage, and is commonly analyzed as an excellent marker of DNA lesions. The purpose of this study was to develop a sensitive method to accurately and rapidly quantify the 8-OHdG by using capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). The method involved the use of specific antibody to detect DNA lesions (8-OHdG) and consecutive fluorescence labeling. Next, the urine sample with 8-OHdG fluorescently labeled along with other constituents was resolved by capillary electrophoretic system and the lesion of interest was detected using fluorescence detector. The limit of detection was 0.18 fmol, which is sufficient sensitivity for detection and quantification of 8-OHdG in untreated urine samples. The relative standard deviation (RSD) was found to be 11.32 % for migration time, and 5.52 % for peak area. To demonstrate the utility of this method, the urinary concentration of 8-OHdG in an Alzheimer’s transgenic mouse model was determined. Collectively, our results indicate that this methodology offers great advantages such as high separation efficiency, good selectivity, low limit of detection (LOD), simplicity and low cost of analysis. PMID:23712533

Urinary Concentrations of Bisphenols and Their Association with Biomarkers of Oxidative Stress in People Living Near E-Waste Recycling Facilities in China.

PubMed

Zhang, Tao; Xue, Jingchuan; Gao, Chuan-zi; Qiu, Rong-liang; Li, Yan-xi; Li, Xiao; Huang, Ming-zhi; Kannan, Kurunthachalam

2016-04-05

In this study, concentrations of bisphenol A (BPA) and seven other bisphenols (BPs) were measured in urine samples collected from people living in and around e-waste dismantling facilities, and in matched reference population from rural and urban areas in China. BPA, bisphenol S (BPS), and bisphenol F (BPF) were frequently detected (detection frequencies: > 90%) in urine samples collected from individuals who live near e-waste facilities, with geometric mean (GM) concentrations of 2.99 (or 3.75), 0.361 (or 0.469), and 0.349 (or 0.435) ng/mL (or μg/g Cre), respectively; the other five BPs were rarely found in urine samples, regardless of the sampling location. The urinary concentrations of BPA and BPF, but not BPS, were significantly higher in individuals from e-waste recycling locations than did individuals from a rural reference location. Our findings indicated that e-waste dismantling activities contribute to human exposure to BPA and BPF. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured in urine as a marker of oxidative stress. In the e-waste dismantling location, urinary 8-OHdG was significantly and positively correlated (p < 0.001) with urinary BPA and BPS, but not BPF; a similar correlation was also observed in reference sites. These findings suggest that BPA and BPS exposures are associated with elevated oxidative stress.

Increased urinary excretion of 8-hydroxydeoxyguanosine in engine room personnel exposed to polycyclic aromatic hydrocarbons

PubMed Central

Nilsson, R; Nordlinder, R; Moen, B; Ovrebo, S; Bleie, K; Skorve, A; Hollund, B; Tagesson, C

2004-01-01

Background: Previous investigations indicate that engine room personnel on ships are exposed to polycyclic aromatic hydrocarbons (PAH) from oil and oil products, with dermal uptake as the major route of exposure. Several PAH are known carcinogens and mutagens. Aims: To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxy-guanosine (8OHdG), in engine room personnel, and to study the association between 8OHdG and 1-hydroxypyrene (1OHP), a biological marker for PAH exposure. Methods: Urine samples were collected from engine room personnel (n = 36) on 10 Swedish and Norwegian ships and from unexposed controls (n = 34) with similar age and smoking habits. The exposure to oils, engine exhaust, and tobacco smoke 24 hours prior to sampling was estimated from questionnaires. The urinary samples were frozen for later analyses of 8OHdG and 1OHP by high performance liquid chromatography. Results: Excretion in urine of 8OHdG (adjusted to density 1.022) was similar for controls (mean 18.0 nmol/l, n = 33), and for those who had been in the engine room without skin contact with oils (mean 18.7 nmol/l, n = 15). Engine room personnel who reported skin contact with oil had increased excretion of 8OHdG (mean 23.2 nmol/l, n = 19). The difference between this group and the unexposed controls was significant. The urinary levels of ln 1OHP and ln 8OHdG were significantly correlated, and the association was still highly significant when the effects of smoking and age were accounted for in a multiple regression analysis. Conclusion: Results indicate that exposure to PAH or possibly other compounds from skin contact with oils in engine rooms may cause oxidative DNA damage. PMID:15258276

Increased urinary excretion of 8-hydroxydeoxyguanosine in engine room personnel exposed to polycyclic aromatic hydrocarbons.

PubMed

Nilsson, R; Nordlinder, R; Moen, B E; Øvrebø, S; Bleie, K; Skorve, A H; Hollund, B E; Tagesson, C

2004-08-01

Previous investigations indicate that engine room personnel on ships are exposed to polycyclic aromatic hydrocarbons (PAH) from oil and oil products, with dermal uptake as the major route of exposure. Several PAH are known carcinogens and mutagens. To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxy-guanosine (8OHdG), in engine room personnel, and to study the association between 8OHdG and 1-hydroxypyrene (1OHP), a biological marker for PAH exposure. Urine samples were collected from engine room personnel (n = 36) on 10 Swedish and Norwegian ships and from unexposed controls (n = 34) with similar age and smoking habits. The exposure to oils, engine exhaust, and tobacco smoke 24 hours prior to sampling was estimated from questionnaires. The urinary samples were frozen for later analyses of 8OHdG and 1OHP by high performance liquid chromatography. Excretion in urine of 8OHdG (adjusted to density 1.022) was similar for controls (mean 18.0 nmol/l, n = 33), and for those who had been in the engine room without skin contact with oils (mean 18.7 nmol/l, n = 15). Engine room personnel who reported skin contact with oil had increased excretion of 8OHdG (mean 23.2 nmol/l, n = 19). The difference between this group and the unexposed controls was significant. The urinary levels of ln 1OHP and ln 8OHdG were significantly correlated, and the association was still highly significant when the effects of smoking and age were accounted for in a multiple regression analysis. Results indicate that exposure to PAH or possibly other compounds from skin contact with oils in engine rooms may cause oxidative DNA damage.

Polymorphic trial in oxidative damage of arsenic exposed Vietnamese.

PubMed

Fujihara, Junko; Soejima, Mikiko; Yasuda, Toshihiro; Koda, Yoshiro; Kunito, Takashi; Iwata, Hisato; Tanabe, Shinsuke; Takeshita, Haruo

2011-10-15

Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 Asp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNPs was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes. Published by Elsevier Inc.

Exposure to polycyclic aromatic hydrocarbons, arsenic and environmental tobacco smoke, nutrient intake, and oxidative stress in Japanese preschool children.

PubMed

Mori, Takuya; Yoshinaga, Jun; Suzuki, Kei; Mizoi, Miho; Adachi, Shu-Ichi; Tao, Hiroaki; Nakazato, Tetsuya; Li, Yun-Shan; Kawai, Kazuaki; Kasai, Hiroshi

2011-07-01

The association between oxidative stress and exposure to environmental chemicals was assessed in a group of Japanese preschool children. The concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 1-hydroxypyrene (1-OHP), inorganic arsenic (iAs) and monomethylarsonic acid (MMA), and cotinine in spot urine samples, collected from 134 children (3-6 yrs) from a kindergarten in Kanagawa, Japan, were measured as biomarkers of oxidative stress or exposure to environmental chemicals. For 76 subjects of the 134, intakes of anti-oxidant nutrients (vitamins A, C, and E, manganese, copper, zinc and selenium (Se)) were estimated from a food consumption survey carried out 2-4 weeks after urine sampling and by urine analysis (Se). The median (min-max) creatinine-corrected concentrations of urinary biomarkers were 4.45 (1.98-12.3), 0.127 (0.04-2.41), 4.78 (1.18-12.7), and 0.62 (<0.6-19.0) μg/g cre for 8-OHdG, 1-OHP, iAs+MMA, and cotinine, respectively. Multiple regression analysis was carried out using 8-OHdG concentration as a dependent variable and urinary biomarkers of exposure and Se intake, intakes of vitamins and biological attributes of the subjects as independent variables. To explain 8-OHdG concentrations, intake of vitamin A and age were significant variables with negative coefficients, while 1-OHP concentration had a positive coefficient. These results indicated that oxidative stress of children is affected by chemical exposure at environmental levels, by nutrient intake and by physiological factors in a complex manner. On the other hand, unstable statistical results due to sub-grouping of subject, based on the availability of food consumption data, were found: the present results should further be validated by future studies with suitable research design. Copyright © 2011 Elsevier B.V. All rights reserved.

The effects of heavy metals and their interactions with polycyclic aromatic hydrocarbons on the oxidative stress among coke-oven workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Tian; Feng, Wei; Kuang, Dan

Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are predominate toxic constituents of particulate air pollution that may be related to the increased risk of cardiopulmonary events. We aim to investigate the effects of the toxic heavy metals (arsenic, As; cadmium, Cd; chromium, Cr; nickel, Ni; and lead, Pb), and their interactions with PAHs on oxidative stress among coke-oven workers. A total of 1333 male workers were recruited in this study. We determined their urinary levels of As, Cd, Cr, Ni, Pb, twelve PAH metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α). Multivariate linear regression models were used to analyze the effects ofmore » these metals and their interactions with PAHs on 8-OHdG and 8-iso-PGF2α levels. It was found that only urinary As and Ni showed marginal or significant positive linear dose-dependent effects on 8-OHdG in this study population, especially among smokers (β=0.103, P=0.073 and β=0.110, P=0.002, respectively). After stratifying all participants by the quartiles of ΣOH-PAH, all five metals showed linear association with 8-OHdG in the highest quartile subgroup (Q4) of ΣOH-PAHs. However, these five urinary metals showed significantly consistent linear associations with 8-iso-PGF2α in all subjects and each stratum. Urinary ΣOH-PAHs can significant modify the effects of heavy metals on oxidative stress, while co-exposure to both high levels of ΣOH-PAHs and heavy metals render the workers with highest 8-OHdG and 8-iso-PGF2α (all P{sub interaction}≤0.005). This study showed evidence on the interaction effects of heavy metals and PAHs on increasing the oxidative stress, and these results warrant further investigation in more longitudinal studies. - Highlights: • Heavy metals and PAHs are predominate toxic constituents of particulate matters. • Urinary As and Ni showed linear dose-dependent effects on 8-OHdG and 8-iso-PGF2α. • PAHs significant interact with toxic metal in increasing 8-OHdG and 8-iso-PGF2α. • Co-exposure to high PAHs and toxic metals contribute to highest oxidative stress.« less

Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers.

PubMed

Zhang, Xu-Hui; Zhang, Xuan; Wang, Xu-Chu; Jin, Li-Fen; Yang, Zhang-Ping; Jiang, Cai-Xia; Chen, Qing; Ren, Xiao-Bin; Cao, Jian-Zhong; Wang, Qiang; Zhu, Yi-Min

2011-04-12

Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI)) exposure can cause DNA damage in electroplating workers. 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%). Urinary 8-OHdG levels were measured by ELISA. Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L) than that in control subjects (1.54 μg/L, P < 0.001). The medians (range) of Olive tail moment, tail length and tail DNA% in exposed workers were 1.13 (0.14-6.77), 11.17 (3.46-52.19) and 3.69 (0.65-16.20), and were significantly higher than those in control subjects (0.14 (0.01-0.39), 3.26 (3.00-4.00) and 0.69 (0.04-2.74), P < 0.001). Urinary 8-OHdG concentration was 13.65 (3.08-66.30) μg/g creatinine in exposed workers and 8.31 (2.94-30.83) μg/g creatinine in control subjects (P < 0.001). The differences of urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA% between these two groups remained significant (P < 0.001) even after stratification by potential confounding factors such as age, gender, and smoking status. Chromium exposure was found to be positively associated with chromium levels in erythrocytes, urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA%. Positive dose-response associations were also found between chromium levels in erythrocytes and Olive tail moment, tail length and tail DNA%. The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage.

Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers

PubMed Central

2011-01-01

Background Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI)) exposure can cause DNA damage in electroplating workers. Methods 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%). Urinary 8-OHdG levels were measured by ELISA. Results Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L) than that in control subjects (1.54 μg/L, P < 0.001). The medians (range) of Olive tail moment, tail length and tail DNA% in exposed workers were 1.13 (0.14-6.77), 11.17 (3.46-52.19) and 3.69 (0.65-16.20), and were significantly higher than those in control subjects (0.14 (0.01-0.39), 3.26 (3.00-4.00) and 0.69 (0.04-2.74), P < 0.001). Urinary 8-OHdG concentration was 13.65 (3.08-66.30) μg/g creatinine in exposed workers and 8.31 (2.94-30.83) μg/g creatinine in control subjects (P < 0.001). The differences of urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA% between these two groups remained significant (P < 0.001) even after stratification by potential confounding factors such as age, gender, and smoking status. Chromium exposure was found to be positively associated with chromium levels in erythrocytes, urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA%. Positive dose-response associations were also found between chromium levels in erythrocytes and Olive tail moment, tail length and tail DNA%. Conclusion The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage. PMID:21481275

Personal exposure to particulate PAHs and anthraquinone and oxidative DNA damages in humans.

PubMed

Wei, Yongjie; Han, In-Kyu; Hu, Min; Shao, Min; Zhang, Junfeng Jim; Tang, Xiaoyan

2010-11-01

Recent studies suggest that DNA oxidative damage be related to the chemical constituents of ambient particles. The purpose of this study was to examine whether particulate polycyclic aromatic hydrocarbons (PAHs) and quinone-structure chemicals increase body burden of oxidative stress in human exposed to heavy traffic volume. We recruited two nonsmoking security guards who worked at a university campus gate near a heavily trafficked road. Each subject wore a personal air sampler for 24h per day to estimate exposures to 24 PAHs and anthraquinone (AnQ) in PM(2.5). Daily pre- and post-work shift spot urines were collected for 29d from each subject. Urine samples were analyzed for 8-hydroxy-2'-deoxyguanosine (8-OHdG). Additionally, using 19 organic tracers other than 24 PAHs and AnQ, a receptor source apportionment model of chemical mass balance was applied to determine the contributions of sources on the PM: gasoline vehicle, diesel vehicle, coal burning, vegetable debris, cooking, natural gas and biomass burning. The relationship among urinary 8-OHdG, individual PAH, and AnQ was demonstrated as follows: the average urinary concentration of 8-OHdG was increased more than three times after 8-h work-shift than those before the work shift. All the 24 PAH and AnQ levels were positively and significantly associated with the post-work urinary 8-OHdG. The results from source apportionment suggest vehicular emission to be the dominant source of personal exposure to PM(2.5). Our finding indicates that personal air exposures to 24 individual PAHs and AnQ originating from traffic emissions are important in increasing oxidative burdens in human body. Copyright © 2010 Elsevier Ltd. All rights reserved.

Smoking modify the effects of polycyclic aromatic hydrocarbons exposure on oxidative damage to DNA in coke oven workers.

PubMed

Yang, Jin; Zhang, Hongjie; Zhang, Huitao; Wang, Wubin; Liu, Yanli; Fan, Yanfeng

2017-07-01

Coke oven emissions containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Numerous epidemiological studies have suggested that oxidative DNA damage may play a pivotal role in the carcinogenic mechanism of lung cancer. Little is known about the effect of interaction between PAHs exposure and lifestyle on DNA oxidative damage. The study population is composed by coke oven workers (365) and water treatment workers (144), and their urinary levels of four PAH metabolites and 8-hydroxydeoxyguanosine (8-OHdG) were determined. Airborne samples of exposed sites (4) and control sites (3) were collected, and eight carcinogenic PAHs were detected by high-performance liquid chromatography. The median values of the sum of eight carcinogenic PAHs and BaP in exposed sites were significantly higher than control sites (P < 0.01). The study found that the urinary PAH metabolites were significantly elevated in coke oven workers (P < 0.01). Multivariate logistic regression analysis revealed that the risk of high levels of urinary 8-OHdG will increase with increasing age, cigarette consumption, and levels of urinary 1-hydroxypyrene, and P for trend were all <0.05. Smoking can significantly modify the effects of urinary 1-hydroxypyrene on high concentrations urinary 8-OHdG, during co-exposure to both light or heavy smoking and high 1-hydroxypyrene levels (OR 4.28, 95% CI 1.32-13.86 and OR 5.05, 95% CI 1.63-15.67, respectively). Our findings quantitatively demonstrate that workers exposed to coke oven fumes and smoking will cause more serious DNA oxidative damage.

Higher dermal exposure of cashiers to BPA and its association with DNA oxidative damage.

PubMed

Lv, Yanshan; Lu, Shaoyou; Dai, Yanyan; Rui, Caiyan; Wang, Yongjun; Zhou, Yuanxiu; Li, Yanru; Pang, Qihua; Fan, Ruifang

2017-01-01

Bisphenol A (BPA) is a widely used chemical in the production of many polycarbonate plastics, epoxy resin linings for food and beverage containers and thermal papers. Oral intakes from the contaminated diets were considered as the predominant source of BPA exposure for humans. However, due to the high levels of BPA on thermal receipts and their wide applications in our daily life, the amount of BPA be transferred to the skin after holding thermal paper should not be underestimated, particularly for cashiers. To investigate the contribution of BPA exposure levels via the dermal contact route and the relationship between BPA exposure level and oxidative DNA damage, six male volunteers were recruited and required to simulate the cashiers' work and handle the thermal receipts during the study period. Triclosan (TCS, an antimicrobial compound used widely in personal health and skin care products) was applied as a reference compound. Their urinary BPA, TCS and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were determined by high performance liquid chromatography/ tandem spectrometer (LC/MS/MS). The results showed that after handling the thermal receipts, the urinary BPA concentrations of volunteers increased 3 times of those before the experimental period. But TCS levels in urine kept stable. There existed a correlation between BPA exposure and 8-OHdG (R 2 =0.237, p<0.001), but not between TCS and 8-OHdG concentrations (R 2 =0.026, p<0.777), indicating that more BPA exposure could lead to higher oxidative DNA damage. That the increases in 8-OHdG levels in urine being almost consistent with those of BPA suggested that handling thermal receipts resulted in the increasing BPA intakes and BPA exposure was correlated with DNA oxidative damage. After 48h of the end of handling thermal receipts, the urinary BPA levels did not descend to the levels before experiment, suggesting that the excretion of BPA via dermal contact was over 48h. BPA exposure through dermal contact route contributed 51.9% to 84% to urinary BPA levels with the GM ratio of 70.9% for cashiers, indicating that it might be seriously underestimated for cashiers according to the previous studies. More attentions should be paid on the exposure of BPA via dermal penetration for cashiers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Urinary 8-hydroxy-2'-deoxyguanosine as a novel biomarker for predicting cardiac events and evaluating the effectiveness of carvedilol treatment in patients with chronic systolic heart failure.

PubMed

Susa, Takehisa; Kobayashi, Shigeki; Tanaka, Takeo; Murakami, Wakako; Akashi, Shintaro; Kunitsugu, Ichiro; Okuda, Shinichi; Doi, Masahiro; Wada, Yasuaki; Nao, Tomoko; Yamada, Jutaro; Ueyama, Takeshi; Okamura, Takayuki; Yano, Masafumi; Matsuzaki, Masunori

2012-01-01

The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment. Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment. U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

PubMed

Sauvain, Jean-Jacques; Setyan, Ari; Wild, Pascal; Tacchini, Philippe; Lagger, Grégoire; Storti, Ferdinand; Deslarzes, Simon; Guillemin, Michel; Rossi, Michel J; Riediker, Michael

2011-05-30

Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

[Association of cooking oil fumes exposure and oxidative DNA damage among occupational exposed populations].

PubMed

Ke, Yue-bin; Xu, Xin-yun; Yuan, Jian-hui; Fang, Shi-song; Liu, Yi-min; Wu, Tang-chun

2010-08-01

Previous investigations indicate that cooks are exposed to polycyclic aromatic hydrocarbons (PAH) from cooking oil fumes (COF). However, Emission of PAH and their carcinogenic potencies from cooking oil fumes sources have not been investigated among cooks. To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), in different groups of cooks and different exposure groups, and to study the association between 8-OHdG and 1-hydroxypyrene (1-OHP), a biological marker for PAH exposure. Urine samples were collected from different groups of cooks (n = 86) and from unexposed controls (n = 36), all are male with similar age and smoking habits. The health status, occupational history, smoking, and alcohol consumption 24 hours prior to sampling was estimated from questionnaires. The urinary samples were frozen for later analyses of 8-OHdG and 1-OHP by high performance liquid chromatography. Excretion in urine of 8-OHdG were similar for controls (mean 1.2 µmol/mol creatinine, n = 36), and for those who had been in the kitchen room with exhaust hood operation (mean 1.5 µmol/mol creatinine, n = 45). COF exposed cooks without exhaust hood operation had increased excretion of 8-OHdG (mean 2.3 µmol/mol creatinine, n = 18). The difference between this group and the unexposed controls was significant. The urinary levels of ln 1-OHP and ln 8-OHdG were still significantly correlated in a multiple regression analysis. Results indicate that exposure to PAH or possibly other compounds in COF may cause oxidative DNA damage.

Advanced data mining approaches in the assessment of urinary concentrations of bisphenols, chlorophenols, parabens and benzophenones in Brazilian children and their association to DNA damage.

PubMed

Rocha, Bruno A; Asimakopoulos, Alexandros G; Honda, Masato; da Costa, Nattane L; Barbosa, Rommel M; Barbosa, Fernando; Kannan, Kurunthachalam

2018-07-01

Human exposure to endocrine disrupting chemicals (EDCs) has received considerable attention over the last three decades. However, little is known about the influence of co-exposure to multiple EDCs on effect-biomarkers such as oxidative stress in Brazilian children. In this study, concentrations of 40 EDCs were determined in urine samples collected from 300 Brazilian children of ages 6-14 years and data were analyzed by advanced data mining techniques. Oxidative DNA damage was evaluated from the urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8OHDG). Fourteen EDCs, including bisphenol A (BPA), methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), 3,4-dihydroxy benzoic acid (3,4-DHB), methyl-protocatechuic acid (OH-MeP), ethyl-protocatechuic acid (OH-EtP), triclosan (TCS), triclocarban (TCC), 2-hydroxy-4-methoxybenzophenone (BP3), 2,4-dihydroxybenzophenone (BP1), bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H 2 O), 2,4-dichlorophenol (2,4-DCP), and 2,5-dichlorophenol (2,5-DCP) were found in >50% of the urine samples analyzed. The highest geometric mean concentrations were found for MeP (43.1 ng/mL), PrP (3.12 ng/mL), 3,4-DHB (42.2 ng/mL), TCS (8.26 ng/mL), BP3 (3.71 ng/mL), and BP1 (4.85 ng/mL), and exposures to most of which were associated with personal care product (PCP) use. Statistically significant associations were found between urinary concentrations of 8OHDG and BPA, MeP, 3,4-DHB, OH-MeP, OH-EtP, TCS, BP3, 2,4-DCP, and 2,5-DCP. After clustering the data on the basis of i) 14 EDCs (exposure levels), ii) demography (age, gender and geographic location), and iii) 8OHDG (effect), two distinct clusters of samples were identified. 8OHDG concentration was the most critical parameter that differentiated the two clusters, followed by OH-EtP. When 8OHDG was removed from the dataset, predictability of exposure variables increased in the order of: OH-EtP > OH-MeP > 3,4-DHB > BPA > 2,4-DCP > MeP > TCS > EtP > BP1 > 2,5-DCP. Our results showed that co-exposure to OH-EtP, OH-MeP, 3,4-DHB, BPA, 2,4-DCP, MeP, TCS, EtP, BP1, and 2,5-DCP was associated with DNA damage in children. This is the first study to report exposure of Brazilian children to a wide range of EDCs and the data mining approach further strengthened our findings of chemical co-exposures and biomarkers of effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reduction of cooking oil fume exposure following an engineering intervention in Chinese restaurants.

PubMed

Pan, Chih-Hong; Shih, Tung-Sheng; Chen, Chiou-Jong; Hsu, Jin-Huei; Wang, Shun-Chih; Huang, Chien-Ping; Kuo, Ching-Tang; Wu, Kuen-Yuh; Hu, Howard; Chan, Chang-Chuan

2011-01-01

A new engineering intervention measure, an embracing air curtain device (EACD), was used to increase the capture efficiency of cooker hoods and reduce cooking oil fume (COF) exposure in Chinese restaurants. An EACD was installed in six Chinese restaurants where the cooks complained of COF exposure. Before- and after-installation measurements were taken to compare changes in particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) in kitchen air, and changes in levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The association between PM and PAHs in air and 8-OHdG and MDA in urine was evaluated by linear mixed-effects regression analysis. Results showed that geometric mean kitchen air levels of PM(10), PM(2.5), PM(1.0) and total particulate PAHs were significantly reduced after the EACDs were introduced. Urinary levels of 8-OHdG and MDA in cooks were also significantly lower after EACD instalment. PM(2.5), PM(1.0) and benzo(a)pyrene (BaP) levels were positively associated with urinary 8-OHdG levels after adjusting for key personal covariates. Urinary MDA levels in cooks were also positively associated with BaP levels after adjusting for key personal covariates. This study demonstrates that the EACD is effective for reducing COF and oxidative stress levels in cooks working in Chinese kitchens.

Exposure to Cooking Oil Fumes and Oxidative Damages: A Longitudinal Study in Chinese Military Cooks

PubMed Central

Lai, Ching-Huang; Jaakkola, Jouni J.K.; Chuang, Chien-Yi; Liou, Saou-Hsing; Lung, Shih-Chun; Loh, Ching-Hui; Yu, Dah-Shyong; Strickland, Paul T.

2014-01-01

Cooking oil fumes contain polycyclic aromatic hydrocarbons (PAHs), heterocyclic aromatic amines, benzene, and formaldehyde which may cause oxidative damages to DNA and lipids. We assessed the relations between exposure to cooking oil fumes (COF) and subsequent oxidative DNA damage and lipid peroxidation among military cooks and office-based soldiers. The study population, including 61 Taiwanese male military cooks and a reference group of 37 office soldiers, collected urine samples pre-shift of the first weekday and post-shift of the fifth workday. We measured airborne particulate PAHs in military kitchens and offices and concentrations of urinary 1-OHP, a biomarker of PAH exposure, urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarkers of oxidative DNA damage, and urinary isoprostane (Isop). Airborne particulate PAHs levels in kitchens significantly exceeded those in office areas. The concentrations of urinary 1-OHP among military cooks increased significantly after 5 days of exposure to COF. Using generalized estimating equation (GEE) analysis adjusting for confounding, a change in log(8-OHdG) and log(Isop) were statistically significantly related to a unit change in log(1-OHP) (regression coefficient [β], β= 0.06, 95% CI 0.001 to 0.12) and (β= 0.07, 95% CI 0.001 to 0.13), respectively. Exposure to PAHs, or other compounds in cooking-oil fumes, may cause both oxidative DNA damage and lipid peroxidation. PMID:22968348

Exposure to cooking oil fumes and oxidative damages: a longitudinal study in Chinese military cooks.

PubMed

Lai, Ching-Huang; Jaakkola, Jouni J K; Chuang, Chien-Yi; Liou, Saou-Hsing; Lung, Shih-Chun; Loh, Ching-Hui; Yu, Dah-Shyong; Strickland, Paul T

2013-01-01

Cooking oil fumes (COF) contain polycyclic aromatic hydrocarbons (PAHs), heterocyclic aromatic amines, benzene, and formaldehyde, which may cause oxidative damages to DNA and lipids. We assessed the relations between exposure to COF and subsequent oxidative DNA damage and lipid peroxidation among military cooks and office-based soldiers. The study population, including 61 Taiwanese male military cooks and a reference group of 37 office soldiers, collected urine samples pre-shift of the first weekday and post-shift of the fifth workday. We measured airborne particulate PAHs in military kitchens and offices and concentrations of urinary 1-OHP, a biomarker of PAH exposure, urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarkers of oxidative DNA damage, and urinary isoprostane (Isop). Airborne particulate PAHs levels in kitchens significantly exceeded those in office areas. The concentrations of urinary 1-OHP among military cooks increased significantly after 5 days of exposure to COF. Using generalized estimating equation analysis adjusting for confounding, a change in log(8-OHdG) and log(Isop) were statistically significantly related to a unit change in log(1-OHP) (regression coefficient (β), β=0.06, 95% CI 0.001-0.12) and (β=0.07, 95% CI 0.001-0.13), respectively. Exposure to PAHs, or other compounds in cooking oil fumes, may cause both oxidative DNA damage and lipid peroxidation.

The effects of heavy metals and their interactions with polycyclic aromatic hydrocarbons on the oxidative stress among coke-oven workers.

PubMed

Wang, Tian; Feng, Wei; Kuang, Dan; Deng, Qifei; Zhang, Wangzhen; Wang, Suhan; He, Meian; Zhang, Xiaomin; Wu, Tangchun; Guo, Huan

2015-07-01

Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are predominate toxic constituents of particulate air pollution that may be related to the increased risk of cardiopulmonary events. We aim to investigate the effects of the toxic heavy metals (arsenic, As; cadmium, Cd; chromium, Cr; nickel, Ni; and lead, Pb), and their interactions with PAHs on oxidative stress among coke-oven workers. A total of 1333 male workers were recruited in this study. We determined their urinary levels of As, Cd, Cr, Ni, Pb, twelve PAH metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α). Multivariate linear regression models were used to analyze the effects of these metals and their interactions with PAHs on 8-OHdG and 8-iso-PGF2α levels. It was found that only urinary As and Ni showed marginal or significant positive linear dose-dependent effects on 8-OHdG in this study population, especially among smokers (β=0.103, P=0.073 and β=0.110, P=0.002, respectively). After stratifying all participants by the quartiles of ΣOH-PAH, all five metals showed linear association with 8-OHdG in the highest quartile subgroup (Q4) of ΣOH-PAHs. However, these five urinary metals showed significantly consistent linear associations with 8-iso-PGF2α in all subjects and each stratum. Urinary ΣOH-PAHs can significant modify the effects of heavy metals on oxidative stress, while co-exposure to both high levels of ΣOH-PAHs and heavy metals render the workers with highest 8-OHdG and 8-iso-PGF2α (all P(interaction)≤0.005). This study showed evidence on the interaction effects of heavy metals and PAHs on increasing the oxidative stress, and these results warrant further investigation in more longitudinal studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers

PubMed Central

2011-01-01

Background Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. Methods Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. Results Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). Conclusions These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations. PMID:21619715

A Simple and Sensitive LC-MS/MS Method for the Determination of Free 8-Hydroxy-2'-Deoxyguanosine in Human Urine

NASA Technical Reports Server (NTRS)

Wang, Zuwei; Smith, Scott M.

2016-01-01

Urinary free 8-hydroxy-2'-deoxyguanosine (8OHdG), an oxidized product of DNA, and is frequently chosen as a biomarker of oxidative stress in humans, including studies of oxidative DNA damage during space flight. It is challenging to accurately and efficiently quantify urinary free 8OHdG in large scale human studies. LC-MS/MS is emerging as a preferable analytical technique owing its high sensitivity, selectivity and efficiency, compared to some traditional methods such as ELISA and HPLC. A simple and sensitive LC-MS/MS method has been developed for the determination of free 8OHdG in human urine. Sample preparation was done by solid phase extraction with a Waters Oasis HLB 96 well plate. A Waters Alliance 2795 HT Separation Module combined with a Quattro Micro tandem mass spectrometer was used as the LC-MS/MS system. The runtime of one injection can be less than 5 minutes using a reversed phase C18 column and an isocratic flow of methanol/water. ESI positive ions were quantified in the multiple reaction modes (MRM) using m/z 284 yields 168 for 8OHdG and m/z 289 yields173 for stable isotope labeled internal standard [(15)N5] 8OHdG. With this method for 8OHdG, a lower limit of quantitation of 1.0 nM (0.28 ng/mL) has been achieved using 100 microliter urine sample. The analytical range is between 1.0 and 100 nM with a correlation coefficient greater than or equal to 0.99. Good reproducibility can be obtained with intra-assay and inter-assay CVs less than or equal to 10% for 8OHdG spiked urine QC samples. This method can be used in high-throughput routine analysis of free 8OHdG in human urine.

Chlorpyrifos exposure in farmers and urban adults: Metabolic characteristic, exposure estimation, and potential effect of oxidative damage.

PubMed

Wang, Lei; Liu, Zhen; Zhang, Junjie; Wu, Yinghong; Sun, Hongwen

2016-08-01

Chlorpyrifos is a widely used organophosphorus pesticide that efficiently protects crops against pests. However, recent studies suggest that severe exposure to chlorpyrifos may present adverse health effects in human. To analyze the exposure level and metabolic characteristics of chlorpyrifos pesticide in urban adults and farmers with/without occupation pesticide contact, the occurrence of urinary chlorpyrifos and methyl chlorpyrifos (CP-me), as well as their metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), was determined in farmers of an agricultural village in China, and in urban adults of a nearby town. The geometric mean (GM) concentrations of TCPy, which is the major marker of chlorpyrifos exposure, were 4.29 and 7.57μg/g-creatinine in urban adults and farmers before pesticide application, respectively. Chlorpyrifos spraying significantly increased the concentrations of urinary TCPy. In the first day after spraying, a GM concentration of 43.7μg/g-creatinine was detected in the urine specimens from farmers, which decreased to 38.1 and 22.8μg/g-creatinine in the second and third day after chlorpyrifos spraying. The ratio of TCPy and its parent compounds, i.e. chlorpyrifos and CP-me, was positively associated with the sum concentration of urinary chlorpyrifos, CP-me, and TCPy, suggesting the increasing metabolic efficiency of chlorpyrifos to TCPy at higher chlorpyrifos exposure levels. To estimate the farmers' occupational exposure to chlorpyrifos pesticide, a new model based on the fitted first-order elimination kinetics of TCPy was established. Occupational chlorpyrifos exposure in a farmer was estimated to be 3.70μg/kg-bw/day (GM), which is an exposure level that is higher than the recommended guideline levels. Significant increase of urinary 8-hydroxydeoxyguanosine (8-OHdG) was observed on the first day after chlorpyrifos spraying, which indicates a potential oxidative damage in farmers. However, urinary 8-OHdG returned to its baseline level within two days. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased levels of oxidative DNA damage attributable to cooking-oil fumes exposure among cooks.

PubMed

Ke, Yuebin; Cheng, Jinquan; Zhang, Zhicheng; Zhang, Renli; Zhang, Zhunzhen; Shuai, Zhihong; Wu, Tangchun

2009-07-01

Previous investigations have indicated that cooks are exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking-oil fumes. However, Emission of PAH and their carcinogenic potencies from cooking oil fumes sources have not been investigated among cooks. To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), in different groups of cooks and different exposure groups, and to study the association between 8-OHdG and 1-hydroxypyrene(1-OHP), a biological marker for PAH exposure. Urine samples were collected from different groups of cooks (n = 86) and from unexposed controls (n = 36); all were male with similar age and smoking habits. The health status, occupational history, smoking, and alcohol consumption 24 h prior to sampling was estimated from questionnaires. The urine samples were frozen for later analyses of 8-OHdG and 1-OHP levels by high-performance liquid chromatography. Excretion in urine of 8-OHdG was similar for controls (mean 1.2micromol/mol creatinine, n = 36), and for those who had been in the kitchen with an exhaust-hood operating (mean 1.5micromol/mol creatinine, n = 45). Cooks exposed to cooking-oil fumes without exhaust-hood operation had significantly increased excretion of 8-OHdG (mean 2.3micromol/mol creatinine, n = 18), compared with controls. The urinary levels of ln 1-OHP and ln 8-OHdG were still significantly correlated in a multiple regression analysis. The results indicate that exposure to PAH or possibly other compounds in cooking-oil fumes may cause oxidative DNA damage.

The Reliability and Predictive Ability of a Biomarker of Oxidative DNA Damage on Functional Outcomes after Stroke Rehabilitation

PubMed Central

Hsieh, Yu-Wei; Lin, Keh-Chung; Korivi, Mallikarjuna; Lee, Tsong-Hai; Wu, Ching-Yi; Wu, Kuen-Yuh

2014-01-01

We evaluated the reliability of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and determined its ability to predict functional outcomes in stroke survivors. The rehabilitation effect on 8-OHdG and functional outcomes were also assessed. Sixty-one stroke patients received a 4-week rehabilitation. Urinary 8-OHdG levels were determined by liquid chromatography–tandem mass spectrometry. The test-retest reliability of 8-OHdG was good (interclass correlation coefficient = 0.76). Upper-limb motor function and muscle power determined by the Fugl-Meyer Assessment (FMA) and Medical Research Council (MRC) scales before rehabilitation showed significant negative correlation with 8-OHdG (r = −0.38, r = −0.30; p < 0.05). After rehabilitation, we found a fair and significant correlation between 8-OHdG and FMA (r = −0.34) and 8-OHdG and pain (r = 0.26, p < 0.05). Baseline 8-OHdG was significantly correlated with post-treatment FMA, MRC, and pain scores (r = −0.34, −0.31, and 0.25; p < 0.05), indicating its ability to predict functional outcomes. 8-OHdG levels were significantly decreased, and functional outcomes were improved after rehabilitation. The exploratory study findings conclude that 8-OHdG is a reliable and promising biomarker of oxidative stress and could be a valid predictor of functional outcomes in patients. Monitoring of behavioral indicators along with biomarkers may have crucial benefits in translational stroke research. PMID:24743892

Increased urinary 8-hydroxy-2'-deoxyguanosine levels in workers exposed to di-(2-ethylhexyl) phthalate in a waste plastic recycling site in China.

PubMed

Wang, Qian; Wang, Li; Chen, Xi; Rao, Kai Min; Lu, Shao You; Ma, Sheng Tao; Jiang, Pu; Zheng, Dan; Xu, Shun Qing; Zheng, Hong Yan; Wang, Jian Shu; Yu, Zhi Qiang; Zhang, Rong; Tao, Yong; Yuan, Jing

2011-07-01

Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in industrial and diverse consumer products. Animal studies indicate DEHP caused developmental, reproductive, and hepatic toxicities. However, human studies of the potential effects of DEHP are limited. The exposed site with a history of over 20 years of waste plastic recycling was located in Hunan Province, China. The reference site without known DEHP pollution source was about 50 km far away from the exposed site. In this study, 181 workers working in plastic waste recycling and 160 gender-age matched farmers were recruited. DEHP concentrations in water and cultivated soil samples, serum thyroid-stimulating hormone, malondialdehyde (MDA), superoxide dismutase (SOD), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and micronuclei frequency in human capillary blood lymphocytes were analyzed. Mean levels of DEHP were greater in environment at the recycling site than at reference site (industry wastewater for the exposed: 42.43 μg/l; well water: 14.20 vs. 0.79 μg/l, pond water: 135.68 vs. 0.37 μg/l, cultivated soil: 13.07 vs. 0.81 mg/kg, p < 0.05 for all). The workers had higher median levels of MDA (3.80 vs. 3.14 nmol/ml) and urinary 8-OHdG (340.37 vs. 268.18 μmol/mol creatinine) and decreased SOD activities (112.15 vs. 123.82 U/ml) than the reference group (p < 0.01 for all). Multivariate analysis revealed that the history of working in waste plastic recycling was an independent risk factor for the increased urinary 8-OHdG levels in the male workers (p < 0.01). The occupational DEHP exposure might contribute to oxidative deoxyribonucleic acid damage in the male workers.

Short-term markers of DNA damage among roofers who work with hot asphalt.

PubMed

Serdar, Berrin; Brindley, Stephen; Dooley, Greg; Volckens, John; Juarez-Colunga, Elizabeth; Gan, Ryan

2016-10-20

Roofers are at increased risk for various malignancies and their occupational exposures to polycyclic aromatic hydrocarbons (PAHs) have been considered as important risk factors. The overall goal of this project was to investigate the usefulness of phosphorylated histone H2AX (γH2AX) as a short-term biomarker of DNA damage among roofers. Blood, urine, and dermal wipe samples were collected from 20 roofers who work with hot asphalt before and after 6 h of work on Monday and Thursday of the same week (4 sampling periods). Particle-bound and gas-phase PAHs were collected using personal monitors during work hours. γH2AX was quantified in peripheral lymphocytes using flow cytometry and 8-hydroxy-2-deoxyguanosine (8-OHdG) was assessed in urine using ELISA. General linear mixed models were used to evaluate associations between DNA damage and possible predictors (such as sampling period, exposure levels, work- and life-style factors). Differences in mean biomarker and DNA damage levels were tested via ANOVA contrasts. Exposure measurements did not show an association with any of the urinary biomarkers or the measures of DNA damage. Naphthalene was the most abundant PAH in gas-phase, while benzo(e)pyrene was the most abundant particle-bound PAH. Post-shift levels of γH2AX and 8-OHdG were higher on both study days, when compared to pre-shift levels. Cigarette smoking was a predictor of γH2AX and urinary creatinine was a predictor of urinary 8-OHdG. Between-subject variance to total variance ratio was 35.3 % for γH2ax and 4.8 % for 8-OHdG. γH2AX is a promising biomarker of DNA damage in occupational epidemiology studies. It has a lower within-subject variation than urinary 8-OHdG and can easily be detected in large scale groups. Future studies that explore the kinetics of H2AX phosphorylation in relation to chemical exposures may reveal the transient and persistent nature of this sensitive biomarker of early DNA damage.

SIRT6 expression and oxidative DNA damage in individuals with prediabetes and type 2 diabetes mellitus.

PubMed

Çalışkan, Z; Mutlu, T; Güven, M; Tunçdemir, M; Niyazioğlu, M; Hacioglu, Y; Dincer, Y

2018-02-05

Sirtuins (SIRTs) is a family of NAD + dependent histone deacetylases. SIRT6 takes play in glucose homeostasis, genomic stability and DNA repair. Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far. We determined SIRT6 expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). SIRT6 gene expression was determined in peripheral blood leukocytes of 70 patients with type 2 diabetes, 50 cases in prediabetic stage and 40 healthy subjects. SIRT6 mRNA levels were determined by quantitive real time- polymerase chain reaction. SIRT6 protein was detected by immunocytochemical staining. Urinary 8-hydroxy deoxyguanosine (8-OHdG) levels were measured by ELISA. There was no significant difference between groups for SIRT6 mRNA level. SIRT6 immunopositivity in T2DM group was lower when compared to those in preDM group (P<0.05). SIRT6 positive cell number in T2DM and preDM groups were lower in comparison to control group (P<0.01 for both), however, when study groups were subdivided into two groups according to their age, the difference between preDM and control groups disappeared in both mid-aged and old-aged groups. The urinary 8-OHdG level was found to be higher in the T2DM group in comparison to preDM group (P<0.05). When age is taken into consideration, urinary 8-OHdG level in the T2DM group was found to be higher than those in both preDM and control groups in the old-aged cases but no significant difference was determined between groups in the mid-aged cases. There was no relation between SIRT6 expression and urinary 8-OHDG excretion. It was concluded that SIRT6 may take play in development of T2DM but this effect seems to be independent from repair of oxidative DNA damage. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of E-waste Recycling on Urinary Metabolites of Organophosphate Flame Retardants and Plasticizers and Their Association with Oxidative Stress.

PubMed

Lu, Shao-You; Li, Yan-Xi; Zhang, Tao; Cai, Dan; Ruan, Ju-Jun; Huang, Ming-Zhi; Wang, Lei; Zhang, Jian-Qing; Qiu, Rong-Liang

2017-02-21

In this study, three chlorinated (Cl-mOPs) and five nonchlorinated (NCl-mOPs) organophosphate metabolites were determined in urine samples collected from participants living in an electronic waste (e-waste) dismantling area (n = 175) and two reference areas (rural, n = 29 and urban, n = 17) in southern China. Bis(2-chloroethyl) phosphate [BCEP, geometric mean (GM): 0.72 ng/mL] was the most abundant Cl-mOP, and diphenyl phosphate (DPHP, 0.55 ng/mL) was the most abundant NCl-mOP. The GM concentrations of mOPs in the e-waste dismantling sites were higher than those in the rural control site. These differences were significant for BCEP (p < 0.05) and DPHP (p < 0.01). Results suggested that e-waste dismantling activities contributed to human exposure to OPs. In the e-waste sites, the urinary concentrations of bis(2-chloro-isopropyl) phosphate (r = 0.484, p < 0.01), BCEP (r = 0.504, p < 0.01), dibutyl phosphate (r = 0.214, p < 0.05), and DPHP (r = 0.440, p < 0.01) were significantly increased as the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative stress, increased. Our results also suggested that human exposure to OPs might be correlated with DNA oxidative stress for residents in e-waste dismantling areas. To our knowledge, this study is the first to report the urinary levels of mOPs in China and examine the association between OP exposure and 8-OHdG in humans.

Urinary 8-hydroxy-2-deoxyguanosine and cognitive function in Puerto Rican adults

USDA-ARS?s Scientific Manuscript database

DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. We, therefore, examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of Puerto Rican adul...

Thermoelectric ELISA for quantification of 8OHdG in a microfluidic device

NASA Astrophysics Data System (ADS)

Nestorova, Gergana

This research demonstrates the feasibility of a novel method for performing thermoelectric enzyme-linked immunosorbent assay (ELISA) in a microfluidic device. The feasibility of the thermoelectric ELISA is demonstrated by measuring the concentration of 8-hydroxy 2-deoxyguanosine (8OHdG) in urine samples from amyloid precursor protein (APP) transgenic mice. The detection method is based on formation of a complex between 8OHdG and anti-8OHdG capture antibody conjugated to biotin. The complex is immobilized over the measuring junctions of a thermopile via biotin streptavidin interaction. The concentration of the analyte is determined by using enzyme linked secondary IgG antibody specific to the primary one. The concentration of 8OHdG is determined by the initiation of an enzymatic reaction between glucose and glucose oxidase that is conjugated to the secondary IgG antibody. The heat released by the reaction of glucose and glucose oxidase is measured using an antimony-bismuth thermopile integrated in a microfluidic device. The amount of heat detected by the sensor is inversely proportional to the concentration of 8OHdG. A standard calibration curve using known concentrations of synthetic 8OHdG is generated and used to determine the concentration of the oxidized guanine in mouse urine samples.

Association of blood lead levels with urinary F2-8α Isoprostane and 8-hydroxy-2-deoxy-Guanosine concentrations in first-grade Uruguayan children

PubMed Central

Roy, Aditi; Queirolo, Elena; Peregalli, Fabiana; Mañay, Nelly; Martínez, Gabriela; Kordas, Katarzyna

2015-01-01

Oxidative stress (OS) is a potential molecular mechanism for lead-induced toxicities, yet, we have limited understanding of the relation between low-level lead (Pb) exposure and OS, especially in children. This cross-sectional study examines the association between blood lead level (BLL) and two OS markers—urinary F2-8α isoprostane or isoprostane (a marker of lipid peroxidation) and 8-hydroxy-2-deoxy-Guanosine or 8-OH-dG (a marker of DNA damage) in 211 children, aged 5–8 years, from Montevideo, Uruguay. The role of dietary intakes of vitamin C and zinc in modifying the relation between BLL and OS was also examined. The mean (SD) BLL of the study children was 4.7 (2.2) μg/dL, with 30.2% children having BLL ≥5 μg/dL, the current reference level set by the US Centre for Disease Control for identifying, monitoring and management of children with elevated BLL. In covariate-adjusted analysis, there was a weak positive association between BLL and urinary isoprostane (adjusted for specific gravity) [β = 0.09, p< 0.1]. No association was found between children’s BLL and urinary 8-OH-dG. Interactions between dietary intakes of vitamin C or zinc and BLL on OS biomarkers were not consistent. However, when BLL and vitamin C or BLL and zinc were modeled together, BLL was independently associated with isoprostane concentration [β = 0.10, p< 0.05] but vitamin C or zinc intake was not. These findings suggest that there may be a potential adverse effect of BLL on OS in children with low-level Pb exposure. There is a need to study the effects of Pb on other OS measures, as well as the role of OS in mediating low-level Pb toxicity on functional outcomes. PMID:25863186

Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats.

PubMed

Nakano, Masako; Onodera, Aya; Saito, Emi; Tanabe, Miyako; Yajima, Kazue; Takahashi, Jiro; Nguyen, Van Chuyen

2008-08-01

The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.

Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: the role of reducing oxidative stress in its protective property.

PubMed

Nam, Soo Min; Lee, Mi Young; Koh, Jang Hyun; Park, Jun Ho; Shin, Jang Yel; Shin, Young Goo; Koh, Sang Baek; Lee, Eun Young; Chung, Choon Hee

2009-02-01

Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n=9), control OLETF rats (n=7) and apocynin-treated OLETF rats (n=9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24h urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.

The effect of sunblock against oxidative stress in farmers: a pilot study

PubMed Central

Kim, Yong-Dae; Yim, Dong-Hyuk; Eom, Sang-Yong; Yeoun Lee, Ji; Kim, Heon

2017-01-01

Farmers are frequently exposed to ultraviolet (UV) radiation which causes various diseases by inducing oxidative stress. This study aimed to assess the effects of sunblock on oxidative stress in the body. Eighty-seven farmers were divided into two groups: those who wore sunblock for five days and those who did not. The total antioxidant capacity (TAC) in urine, which is an antioxidant indicator, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in urine, an oxidative stress indicator, were measured. The urinary TAC of sunblock users was significantly higher than that of non-users, but urinary 8-OHdG levels were not significantly different. Even after adjustment for potential confounders, urinary TAC was found to be markedly increased with sunblock usage. These results suggest that sunblock is effective in preventing oxidative stress among farmers. In addition, they show that urinary TAC can be used as a good effect marker of oxidative stress caused by UV exposure. PMID:28808206

Physicochemistry and cardiovascular toxicity of metal fume PM2.5: a study of human coronary artery endothelial cells and welding workers

PubMed Central

Lai, Chane-Yu; Lai, Ching-Huang; Chuang, Hsiao-Chi; Pan, Chih-Hong; Yen, Cheng-Chieh; Lin, Wen-Yi; Chen, Jen-Kun; Lin, Lian-Yu; Chuang, Kai-Jen

2016-01-01

Occupational exposure to welding fumes causes a higher incidence of cardiovascular disease; however, the association remains unclear. To clarify the possible association, exposure assessment of metal fumes with an aerodynamic diameter of <2.5 μm (PM2.5) in welding and office areas was characterized in a shipyard in Taiwan. Cardiovascular toxicity caused by PM2.5 was determined in workers (in both the welding and office areas). Significant amounts of bimodal metal fume particles with count median diameters (CMDs) of 14.1~15.1 and 126.3~135.8 nm were produced in the shipyard. Metal fume PM2.5 resulted in decreased cell viability and increased levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin (IL)-6, and nitric oxide (NO) in human coronary artery epithelial cells (HCAECs). We recruited 118 welding workers and 45 office workers for a personal PM2.5 exposure assessment and determination of urinary levels of 8-OHdG, 8-iso-prostaglandin F2α (8-iso-PGF2α), and various metals. We observed that a 10-μg/m3 increase in the mean PM2.5 concentration was associated with a 2.15% increase in 8-OHdG and an 8.43% increase in 8-iso-PGF2α in welding workers. Both 8-OHdG and 8-iso-PGF2α were associated with Fe and Zn in the urine. In conclusion, metal fume PM2.5 could increase the risk of cardiovascular toxicity after inhalation. PMID:27641436

Physicochemistry and cardiovascular toxicity of metal fume PM2.5: a study of human coronary artery endothelial cells and welding workers.

PubMed

Lai, Chane-Yu; Lai, Ching-Huang; Chuang, Hsiao-Chi; Pan, Chih-Hong; Yen, Cheng-Chieh; Lin, Wen-Yi; Chen, Jen-Kun; Lin, Lian-Yu; Chuang, Kai-Jen

2016-09-19

Occupational exposure to welding fumes causes a higher incidence of cardiovascular disease; however, the association remains unclear. To clarify the possible association, exposure assessment of metal fumes with an aerodynamic diameter of <2.5 μm (PM2.5) in welding and office areas was characterized in a shipyard in Taiwan. Cardiovascular toxicity caused by PM2.5 was determined in workers (in both the welding and office areas). Significant amounts of bimodal metal fume particles with count median diameters (CMDs) of 14.1~15.1 and 126.3~135.8 nm were produced in the shipyard. Metal fume PM2.5 resulted in decreased cell viability and increased levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin (IL)-6, and nitric oxide (NO) in human coronary artery epithelial cells (HCAECs). We recruited 118 welding workers and 45 office workers for a personal PM2.5 exposure assessment and determination of urinary levels of 8-OHdG, 8-iso-prostaglandin F2α (8-iso-PGF2α), and various metals. We observed that a 10-μg/m(3) increase in the mean PM2.5 concentration was associated with a 2.15% increase in 8-OHdG and an 8.43% increase in 8-iso-PGF2α in welding workers. Both 8-OHdG and 8-iso-PGF2α were associated with Fe and Zn in the urine. In conclusion, metal fume PM2.5 could increase the risk of cardiovascular toxicity after inhalation.

Physicochemistry and cardiovascular toxicity of metal fume PM2.5: a study of human coronary artery endothelial cells and welding workers

NASA Astrophysics Data System (ADS)

Lai, Chane-Yu; Lai, Ching-Huang; Chuang, Hsiao-Chi; Pan, Chih-Hong; Yen, Cheng-Chieh; Lin, Wen-Yi; Chen, Jen-Kun; Lin, Lian-Yu; Chuang, Kai-Jen

2016-09-01

Occupational exposure to welding fumes causes a higher incidence of cardiovascular disease; however, the association remains unclear. To clarify the possible association, exposure assessment of metal fumes with an aerodynamic diameter of <2.5 μm (PM2.5) in welding and office areas was characterized in a shipyard in Taiwan. Cardiovascular toxicity caused by PM2.5 was determined in workers (in both the welding and office areas). Significant amounts of bimodal metal fume particles with count median diameters (CMDs) of 14.1~15.1 and 126.3~135.8 nm were produced in the shipyard. Metal fume PM2.5 resulted in decreased cell viability and increased levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin (IL)-6, and nitric oxide (NO) in human coronary artery epithelial cells (HCAECs). We recruited 118 welding workers and 45 office workers for a personal PM2.5 exposure assessment and determination of urinary levels of 8-OHdG, 8-iso-prostaglandin F2α (8-iso-PGF2α), and various metals. We observed that a 10-μg/m3 increase in the mean PM2.5 concentration was associated with a 2.15% increase in 8-OHdG and an 8.43% increase in 8-iso-PGF2α in welding workers. Both 8-OHdG and 8-iso-PGF2α were associated with Fe and Zn in the urine. In conclusion, metal fume PM2.5 could increase the risk of cardiovascular toxicity after inhalation.

Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

PubMed

Graczyk, Halshka; Lewinski, Nastassja; Zhao, Jiayuan; Sauvain, Jean-Jacques; Suarez, Guillaume; Wild, Pascal; Danuser, Brigitta; Riediker, Michael

2016-06-10

Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is recommended that additional exposure metrics such as PNC are considered for occupational risk assessments. Our findings highlight the importance of increasing awareness of TIG welding fume toxicity, especially given the realities of welding workplaces that may lack ventilation; and beliefs among interviewed welders that TIG represents a cleaner and safer welding process.

Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pei, Qiuling, E-mail: 924969007@qq.com; Ma, Ning; Zhang, Jing

There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosismore » was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic. -- Highlights: ► Male inhabitants were investigated from an As-endemic region of China. ► 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs). ► 8-OHdG staining of PMN nuclei was paralleled by increased debris of cells. ► Oxidative DNA damage of PMNs is associated with arsenic-related skin lesions.« less

Adverse health effects of child labor: high exposure to chromium and oxidative DNA damage in children manufacturing surgical instruments.

PubMed

Sughis, Muhammad; Nawrot, Tim S; Haufroid, Vincent; Nemery, Benoit

2012-10-01

A considerable part of the worldwide production of surgical instruments takes place in Sialkot, Pakistan. Many children work in hazardous conditions in this industry. We investigated exposure to metals and possible health effects among children working in surgical instruments manufacturing units compared with schoolchildren from the same city. In a cross-sectional study we studied a convenience sample of 104 male children (10-14 years of age) working in surgical instruments manufacturing units and 75 male children of similar age from a school in Sialkot, Pakistan. A respiratory questionnaire was administered, spirometry was performed, and blood pressure was measured. In a spot urine sample, concentrations of metals were measured by inductively coupled plasma mass spectrometry and 8-hydroxydeoxyguanosine (8OHdG, reflecting oxidative DNA damage) by ELISA. The working children reported more asthma (10% vs. 0%; p = 0.005) and dry cough at night (36% vs. 20%; p = 0.02) than did the schoolchildren, but there were no significant differences in pulmonary function or blood pressure. The urinary concentration of chromium was 35 times higher in working children [geometric mean, 23.0 µg/L; 25th-75th percentile, 8.38-58.6] than in schoolchildren [0.66 µg/L; 0.38-1.09)], and largely in excess of the occupational Biological Exposure Index for adult workers (25 µg/L). Urinary 8-OHdG concentrations were not significantly higher in working children than in schoolchildren (19.3 vs. 17.6 µg/g creatinine, p = 0.4), but were significantly correlated with urinary nickel (r = 0.41; p < 0.0001) and with a composite index of metal exposure (r = 0.46; p < 0.0001). Children working in the surgical instruments manufacturing industry had substantial exposure to several metals, especially chromium and nickel, which are established carcinogens. Exposure to nickel was associated with evidence of increased oxidative DNA damage.

Adverse Health Effects of Child Labor: High Exposure to Chromium and Oxidative DNA Damage in Children Manufacturing Surgical Instruments

PubMed Central

Sughis, Muhammad; Nawrot, Tim S.; Haufroid, Vincent

2012-01-01

Background: A considerable part of the worldwide production of surgical instruments takes place in Sialkot, Pakistan. Many children work in hazardous conditions in this industry. Objective: We investigated exposure to metals and possible health effects among children working in surgical instruments manufacturing units compared with schoolchildren from the same city. Methods: In a cross-sectional study we studied a convenience sample of 104 male children (10–14 years of age) working in surgical instruments manufacturing units and 75 male children of similar age from a school in Sialkot, Pakistan. A respiratory questionnaire was administered, spirometry was performed, and blood pressure was measured. In a spot urine sample, concentrations of metals were measured by inductively coupled plasma mass spectrometry and 8-hydroxydeoxyguanosine (8OHdG, reflecting oxidative DNA damage) by ELISA. Results: The working children reported more asthma (10% vs. 0%; p = 0.005) and dry cough at night (36% vs. 20%; p = 0.02) than did the schoolchildren, but there were no significant differences in pulmonary function or blood pressure. The urinary concentration of chromium was 35 times higher in working children [geometric mean, 23.0 µg/L; 25th–75th percentile, 8.38–58.6] than in schoolchildren [0.66 µg/L; 0.38–1.09)], and largely in excess of the occupational Biological Exposure Index for adult workers (25 µg/L). Urinary 8-OHdG concentrations were not significantly higher in working children than in schoolchildren (19.3 vs. 17.6 µg/g creatinine, p = 0.4), but were significantly correlated with urinary nickel (r = 0.41; p < 0.0001) and with a composite index of metal exposure (r = 0.46; p < 0.0001). Conclusions: Children working in the surgical instruments manufacturing industry had substantial exposure to several metals, especially chromium and nickel, which are established carcinogens. Exposure to nickel was associated with evidence of increased oxidative DNA damage. PMID:22739056

Positive Association between Urinary Concentration of Phthalate Metabolites and Oxidation of DNA and Lipid in Adolescents and Young Adults

NASA Astrophysics Data System (ADS)

Lin, Chien-Yu; Chen, Pau-Chung; Hsieh, Chia-Jung; Chen, Chao-Yu; Hu, Anren; Sung, Fung-Chang; Lee, Hui-Ling; Su, Ta-Chen

2017-03-01

Phthalate has been used worldwide in various products for years. Little is known about the association between phthalate exposure and biomarkers of oxidative stress in adolescents and young adults. Among 886 subjects recruited from a population-based cohort during 2006 to 2008, 751 subjects (12-30 years) with complete phthalate metabolites and oxidation stress measurement were enrolled in this study. Nine urine phthalate metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso prostaglandin F2α (8-isoPGF2α) were measured in urine to assess exposure and oxidative stress to DNA and lipid, respectively. Multiple linear regression analysis revealed that an ln-unit increase in mono-methyl phthalate (MMP) concentration in urine was positively associated with an increase in urine biomarkers of oxidative stress (in μg/g creatinine of 0.098 ± 0.028 in 8-OHdG; and 0.253 ± 0.051 in 8-isoPGF2α). There was no association between other eight phthalate metabolite concentrations and oxidative stress. In conclusion, a higher MMP concentration in urine was associated with an increase in markers of oxidative stress to DNA and lipid in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to phthalate and oxidative stress.

Oxidative DNA damage during sleep periods among nightshift workers.

PubMed

Bhatti, Parveen; Mirick, Dana K; Randolph, Timothy W; Gong, Jicheng; Buchanan, Diana Taibi; Zhang, Junfeng Jim; Davis, Scott

2016-08-01

Oxidative DNA damage may be increased among nightshift workers because of suppression of melatonin, a cellular antioxidant, and/or inflammation related to sleep disruption. However, oxidative DNA damage has received limited attention in previous studies of nightshift work. From two previous cross-sectional studies, urine samples collected during a night sleep period for 217 dayshift workers and during day and night sleep (on their first day off) periods for 223 nightshift workers were assayed for 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, using high-performance liquid chromatography with electrochemical detection. Urinary measures of 6-sulfatoxymelatonin (aMT6s), a marker of circulating melatonin levels, and actigraphy-based sleep quality data were also available. Nightshift workers during their day sleep periods excreted 83% (p=0.2) and 77% (p=0.03) of the 8-OH-dG that dayshift workers and they themselves, respectively, excreted during their night sleep periods. Among nightshift workers, higher aMT6s levels were associated with higher urinary 8-OH-dG levels, and an inverse U-shaped trend was observed between 8-OH-dG levels and sleep efficiency and sleep duration. Reduced excretion of 8-OH-dG among nightshift workers during day sleep may reflect reduced functioning of DNA repair machinery, which could potentially lead to increased cellular levels of oxidative DNA damage. Melatonin disruption among nightshift workers may be responsible for the observed effect, as melatonin is known to enhance repair of oxidative DNA damage. Quality of sleep may similarly impact DNA repair. Cellular levels of DNA damage will need to be evaluated in future studies to help interpret these findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China.

PubMed

Lu, Shao-You; Li, Yan-Xi; Zhang, Jian-Qing; Zhang, Tao; Liu, Gui-Hua; Huang, Ming-Zhi; Li, Xiao; Ruan, Ju-Jun; Kannan, Kurunthachalam; Qiu, Rong-Liang

2016-09-01

Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑10OH-PAHs determined in e-waste recycling area (GM: 25.4μg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7μg/g Cre) and urban (10.9μg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6μg/g Cre) showed significantly higher (p<0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2μg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4μg/g Cre) and non-smokers (24.7μg/g Cre) were not significant (p>0.05) in e-waste dismantling sites, while these differences were significant (p<0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ10OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r=0.284, p<0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of a fruit-vegetable dietary pattern on oxidative stress and genetic damage in coke oven workers: a cross-sectional study.

PubMed

Xie, Zheng; Lin, Haijiang; Fang, Renfei; Shen, Weiwei; Li, Shuguang; Chen, Bo

2015-05-06

Coke oven workers (COWs) are exposed to high level of genotoxic chemicals that induce oxidative stress and genetic damage. The dietary intake of certain types of foods may reverse these effects. We conducted a cross-sectional study with 51 topside COWs, 79 other COWs, and 67 controls, to assess the effects of dietary patterns on oxidative stress and genetic damage. Compared to the controls, both topside and other COWs had significantly higher urinary 1-hydroxypyrene levels, serum oxidant levels [malondialdehyde, (MDA)], and genetic damage [micronucleus (MN) frequency & 8-oxo-2'-deoxyguanosine (8-OH-dG)], but lower antioxidant levels [superoxide dismutase (SOD) and glutathione peroxidase, (GPx)]. The fruit-vegetable (FV) dietary pattern was positively correlated with serum SOD levels and negative correlated with serum MDA, MN frequency, and urinary 8-OH-dG. COWs with an FV patter in the highest quartile (Q4) had significantly increased antioxidant levels (SOD and GPx) and decreased oxidant levels (MDA) and genetic damage (MN frequency and 8-OH-dG) than those with an FV pattern in the lowest quartile (Q1). Compared to control subjects, COWs had increased oxidative stress and genetic damage. A FV dietary pattern may reverse oxidative stress and genetic damage in COWs.

Generic epitaxial graphene biosensors for ultrasensitive detection of cancer risk biomarker

NASA Astrophysics Data System (ADS)

Tehrani, Z.; Burwell, G.; Mohd Azmi, M. A.; Castaing, A.; Rickman, R.; Almarashi, J.; Dunstan, P.; Miran Beigi, A.; Doak, S. H.; Guy, O. J.

2014-09-01

A generic electrochemical method of ‘bioreceptor’ antibody attachment to phenyl amine functionalized graphitic surfaces is demonstrated. Micro-channels of chemically modified multi-layer epitaxial graphene (MLEG) have been used to provide a repeatable and reliable response to nano-molar (nM) concentrations of the cancer risk (oxidative stress) biomarker 8-hydroxydeoxyguanosine (8-OHdG). X-ray photoelectron spectroscopy, Raman spectroscopy are used to characterize the functionalized MLEG. Confocal fluorescence microscopy using fluorescent-labelled antibodies indicates that the anti-8-OHdG antibody selectively binds to the phenyl amine-functionalized MLEG’s channel. Current-voltage measurements on functionalized channels showed repeatable current responses from antibody-biomarker binding events. This technique is scalable, reliable, and capable of providing a rapid, quantitative, label-free assessment of biomarkers at nano-molar (<20 nM) concentrations in analyte solutions. The sensitivity of the sensor device was investigated using varying concentrations of 8-OHdG, with changes in the sensor’s channel resistance observed upon exposure to 8-OHdG. Detection of 8-OHdG concentrations as low as 0.1 ng ml-1 (0.35 nM) has been demonstrated. This is five times more sensitive than reported enzyme linked immunosorbent assay tests (0.5 ng ml-1).

Biomarkers of exposure to polycyclic aromatic hydrocarbons (PAHs) and DNA damage: a cross-sectional pilot study among roofers in South Florida

PubMed Central

Lee, David; Dou, Zihong

2012-01-01

Objective The main goal of this pilot study was to assess the technical and logistic feasibility of a future study. The research hypothesis is that occupational exposures to polycyclic aromatic hydrocarbons (PAHs) are associated with increased risk of DNA damage among roofers who work with hot asphalt. Design This is a cross-sectional pilot study. Setting The study included roofers from four different construction sites in Miami-Dade County, Florida. Participants 19 roofers were recruited (six Hispanics and 13 African–Americans, all male), all of whom were eligible (no history of cancer and no history of chronic diseases of kidneys or liver). All participants provided pre-shift samples and 18 provided post-shift samples. Samples of one participant were excluded from the final analyses as they were considered unreliable. Results Levels of urinary PAH metabolites increased during 6 h of work. Linear regression models of post-shift metabolites included their pre-shift levels, post-shift urinary creatinine levels (for models of 1-OHPyr and 9-OHPhe), and skin burn due to contact with hot asphalt (for models of 1-OHPyr and 1-OHNap). Pre-shift levels of urinary 8-OHdG were not associated with any of the variables considered. For post-shift levels of 8-OHdG, however, post-shift 1-OHPyr (95% CI 0.091 to 0.788) and use of protective gloves (95% CI −1.57 to −0.61) during work explained 86.8% of its variation. Overall, highest levels of urinary PAH metabolites and of 8-OHdG were observed among workers who reported having skin burn and who did not use gloves during work. Conclusions Urinary 1-OHPyr is a promising predictor of oxidative DNA damage among roofers. Work-related skin burn and use of protective gloves appear to influence PAH exposure and DNA damage levels in this group, suggesting the importance of dermal absorption. PMID:22815468

Associations between urinary biomarkers of oxidative stress and air pollutants observed in a randomized crossover exposure to steel mill emissions.

PubMed

Pelletier, Guillaume; Rigden, Marc; Kauri, Lisa Marie; Shutt, Robin; Mahmud, Mamun; Cakmak, Sabit; Kumarathasan, Premkumari; Thomson, Errol M; Vincent, Renaud; Broad, Gayle; Liu, Ling; Dales, Robert

2017-04-01

The effects of industrial air pollution on human health have not been as thoroughly investigated as those of urban air pollution which originates mostly from automotive transport. To better assess the health impacts of point sources of industrial air pollution, a randomized crossover exposure study was conducted. Sixty one young and healthy volunteers were randomly assigned to spend five consecutive eight-hour days near a steel mill or at a location five kilometres away. After a nine or sixteen-day washout period, volunteers spent another five consecutive days at the second site. Meteorological conditions and air pollutants were monitored at both exposure sites. On each exposure day, the first morning urine was collected along with a second urine sample obtained immediately before leaving the exposure site at the end of the day. Urinary levels of biomarkers of oxidative stress 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage), malondialdehyde (MDA, a biomarker of lipid peroxidation), 8-isoprostane (8-IsoP, a bioactive metabolite resulting from the peroxidation of arachidonic acid) and Vascular Endothelial Growth Factor (VEGF, involved in response to oxidative stress) were measured. According to mixed-effects linear regression models, intra-individual variations in 8-OHdG urinary levels were significantly associated with exposure site, but surprisingly, lower levels were observed at the steel mill site. Delayed, temporally-defined associations with specific air pollutants were observed for 8-OHdG, 8-IsoP and VEGF. However, these associations were subtle, presented complex patterns and their biological consequences remain unclear. Crown Copyright © 2016. Published by Elsevier GmbH. All rights reserved.

Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes--Biomarkers as a possible tool for early disease detection for rural screening.

PubMed

Maschirow, L; Khalaf, K; Al-Aubaidy, H A; Jelinek, H F

2015-06-01

This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes. Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects. While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant. The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings. Copyright © 2015. Published by Elsevier Inc.

Influence of green tea catechins on oxidative stress metabolites at rest and during exercise in healthy humans.

PubMed

Sugita, Masaaki; Kapoor, Mahendra P; Nishimura, Akinobu; Okubo, Tsutomu

2016-03-01

The aim of this study was to investigate the effects of green tea catechins (GTC) on oxidative stress metabolites in healthy individuals while at rest and during exercise. The effects investigated included response to fat metabolism, blood lactate concentrations, and rating of perceived exertion. In a paralleled, crossover, randomized controlled study, 16 trained male gymnastic students were randomly divided into two groups. The rest group (n = 8; GTC-NEX) received a single dose of 780 mg GTC with water but no exercise; the exercise group (n = 8; GTC-EX) received a similar dose of GTC but were instructed to exercise. This was followed by a crossover study with similar exercise regime as a placebo group (PL-EX) that received water only. Blood samples were collected at baseline and after 60 and 120 min of GTC intake. Oxidative stress blood biomarkers using the diacron reactive oxygen metabolite (d-ROMs) and biological antioxidant potential (BAP) tests; urinary 8-hydroxydeoxyguanosine (8-OHdG); 8-OHdG/creatinine; and blood lactate concentrations were analyzed. During the cycle ergometer exercise, volume of maximal oxygen uptake, volume of oxygen consumption, volume of carbon dioxide, and respiratory exchange ratio were measured from a sample of respiratory breath gas collected during low, moderate, and high intensity exercising, and the amount of fat burning and sugar consumption were calculated. Analysis of variance was used to determine statistical significance (P < 0.05) between and among the groups. Levels of postexercise oxidative stress metabolites BAP and d-ROMs were found significant (P < 0.0001) in the PL-EX and GTC-EX groups, and returned to pre-exercise levels after the recovery period. Levels of d-ROMs showed no significant difference from baseline upon GTC intake followed by resting and a resting recovery period in the GTC-NEX group. BAP levels were significant upon GTC intake followed by resting (P = 0.04), and after a resting recovery period (P = 0.0006) in the GTC-NEX group. Urinary 8-OHdG levels were significant (P < 0.005) for all groups after the recovery period. A significant difference was noticed between the ratios of resting BAP to d-ROMs and exercise-induced BAP to d-ROMs (P = 0.022) after 60 min of GTC intake, as well as resting 8-OHdG and exercise-induced 8-OHdG levels (P = 0.004) after the recovery period. Oxidative potentials were higher when exercise was performed at low to moderate intensity, accompanied by lower blood lactate concentration and higher amounts of fat oxidation. The results of the present study indicate that single-dose consumption of GTC influences oxidative stress biomarkers when compared between the GTC-NEX and GTC-EX groups, which could be beneficial for oxidative metabolism at rest and during exercise, possibly through the catechol-O-methyltransferase mechanism that is most often cited in previous studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased levels of oxidative DNA damage in pesticide sprayers in Thessaly Region (Greece). Implications of pesticide exposure.

PubMed

Koureas, Michalis; Tsezou, Aspasia; Tsakalof, Andreas; Orfanidou, Timoklia; Hadjichristodoulou, Christos

2014-10-15

The widespread use of pesticides substances nowadays largely guarantees the protection of crops and people from undesired pests. However, exposure to pesticides was related to a variety of human health effects. The present study was conducted in the region of Thessaly which is characterized by intensive agricultural activities and wide use of pesticides. The study aimed at estimating the oxidative damage to DNA in different subpopulations in Thessaly region (Greece) and investigating its correlation with exposure to pesticides and other potential risk factors. In total, the study involved 80 pesticide sprayers, 85 rural residents and 121 individuals, inhabitants of the city of Larissa. Demographic characteristics, habits, medical history and exposure history of the participants to pesticides were recorded by personal interviews. Blood and urine samples were collected from all participants. For the measurement of exposure to organophosphorus insecticides, dialkylphosphate (DAP) metabolites were quantified in urine, by gas chromatography-mass spectrometry. Genomic DNA was extracted from peripheral blood samples and the oxidation by-product 8-hydroxydeoxyguanosine (8-OHdG) was determined by Enzyme Immuno-Assay. Urinary metabolite concentrations were not associated with 8-OHdG levels but it was found that pesticide sprayers had significantly higher levels of 8-OHdG (p=0.007) in comparison to the control group. Last season's exposure to insecticides and fungicides, expressed as total area treated multiplied by the number of applications, showed a statistically significant association with the risk of having high 8-OHdG levels [RR: 2.19 (95%CI:1.09-4.38) and RR: 2.32 (95% CI:1.16-4.64) respectively]. Additionally, from the subgroups of pesticides examined, seasonal exposure to neonicotinoid insecticides [RR: 2.22 (95% CI:1.07-4.63)] and glufosinate ammonium [RR: 3.26 (95% CI:1.38-7.69)] was found to have the greater impact on 8-OHdG levels. This study produced findings that support the hypothesis that pesticide exposure is involved in the induction of oxidative damage to DNA and identified chemical groups of pesticides which should be given greater attention in future investigations. Copyright © 2014 Elsevier B.V. All rights reserved.

Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects

PubMed Central

Kikuchi, Masahiro; Ushida, Yusuke; Shiozawa, Hirokazu; Umeda, Rumiko; Tsuruya, Kota; Aoki, Yudai; Suganuma, Hiroyuki; Nishizaki, Yasuhiro

2015-01-01

AIM: To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants. METHODS: In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme. RESULTS: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers, ALT [median (interquartile range), before: 54.0 (34.5-79.0) vs after supplementation: 48.5 (33.3-65.3) IU/L, P < 0.05] and γ-GTP [before: 51.5 (40.8-91.3) vs after: 50.0 (37.8-85.3) IU/L, P < 0.05], as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHdG, an established oxidative stress marker, was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66 (5.51-9.03) vs after: 5.49 (4.89-6.66) ng/mg-creatinine, P < 0.05]. The reduction of urinary 8-OHdG was significantly correlated with decreased levels of both ALT and γ-GTP [∆8-OHdG and ∆ALT: Spearman r (r) 0.514 and P = 0.012, ∆8-OHdG and ∆γ-GTP: r = 0.496 and P = 0.016]. Intake of BS extract prevented NDMA-induced chronic liver failure in rats, which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST (86.6 ± 95.2 vs 107.8 ± 7.7 IU/g, P < 0.01). CONCLUSION: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress. PMID:26604653

In vitro study of DNA Adduct 8-OHdG Formation by using Bisphenol A in Calf Thymus DNA and 2’-Deoxyguanosine

NASA Astrophysics Data System (ADS)

Budiawan; Cahaya Dani, Intan; Bakri, Ridla; Handayani, Sri; Ratna Dewi, Evi

2018-01-01

The in vitro study of DNA Adduct 8-OHdG Formation due to BisphenolA (BPA) as xenobiotics has been conducted by using calf thymus DNA and 2’deoxyguanosine. The method of study was conducted by incubating calf thymus DNA and 2’dG with compounds trigger to radicals in the variation of pH (7.4 and 8.4), temperature (37°C and 60°C), and BPA concentrations (2 ppm and 10 ppm). To represent the work of CYP 450 enzyme in metabolic process of xenobiotics in the body and the effect of metal presence to the formation of radicals that can lead to 8-OHdG formation, we used iron(II) solution and also fenton reagent (Fe(II) and H2O2). The DNA used has 1.8 purity ratio (checked at λ260/λ280 by using Spectrophotometry UV-Vis). The results by using HPLC method showed that BPA could interact with DNA and DNA base (represent as calf thymus and 2’dG) and potentially induced 8-OHdG formation. The presence of iron(II) metal and Fenton reagent also induced the higher 8-OHdG formation. The higher of pH, temperature and concentrations also lead to 8-OHdG formation (ranger between 4 - 70 ppb).

A novel aptamer-based online magnetic solid phase extraction method for the selective determination of 8-hydroxy-2'-deoxyguanosine in human urine.

PubMed

Gan, Haijiao; Xu, Hui

2018-05-30

In this work, an innovative magnetic aptamer adsorbent (Fe 3 O 4 -aptamer MNPs) was synthesized for the selective extraction of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Amino-functionalized-Fe 3 O 4 was crosslinked with 8-OHdG aptamer by glutaraldehyde and fixed into a steel stainless tube as the sorbent of magnetic solid phase extraction (MSPE). After selective extraction by the aptamer adsorbent, the adsorbed 8-OHdG was desorbed dynamically and online analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS). The synthesized sorbent presented outstanding features, including specific selectivity, high enrichment capacity, stability and biocompatibility. Moreover, this proposed MSPE-HPLC-MS can achieve adsorption and desorption operation integration, greatly simplify the analysis process and reduce human errors. When compared with offline MSPE, a sensitivity enhancement of 800 times was obtained for the online method. Some experimental parameters such as the amount of the sorbent, sample flow rate and sample volume, were optimized systematically. Under the optimal conditions, low limit of detection (0.01 ng mL -1 , S/N = 3), limit of quantity (0.03 ng mL -1 , S/N = 10) and wide linear range with a satisfactory correlation coefficient (R 2  ≥ 0.9992) were obtained. And the recoveries of 8-OHdG in the urine samples varied from 82% to 116%. All these results revealed that the method is simple, rapid, selective, sensitive and automated, and it could be expected to become a potential approach for the selective determination of trace 8-OHdG in complex urinary samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Constructing a novel 8-hydroxy-2'-deoxyguanosine electrochemical sensor and application in evaluating the oxidative damages of DNA and guanine.

PubMed

Guo, Zhipan; Liu, Xiuhui; Liu, Yuelin; Wu, Guofan; Lu, Xiaoquan

2016-12-15

8-Hydroxy-2'-deoxyguanosine (8-OHdG) is commonly identified as a biomarker of oxidative DNA damage. In this work, a novel and facile 8-OHdG sensor was developed based on the multi-walled carbon nanotubes (MWCNTs) modified glassy carbon electrode (GCE). It exhibited good electrochemical responses toward the oxidation of 8-OHdG, and the linear ranges were 5.63×10(-8)-6.08×10(-6)M and 6.08×10(-6)-1.64×10(-5)M, with the detection limit of 1.88×10(-8)M (S/N=3). Moreover, the fabricated sensor was applied for the determination of 8-OHdG generated from damaged DNA and guanine, respectively, and the oxidation currents of 8-OHdG increased along with the damaged DNA and guanine within certain concentrations. These results could be used to evaluate the DNA damage, and provide useful information on diagnosing diseases caused by mutation and deficiency of the immunity system. Copyright © 2016 Elsevier B.V. All rights reserved.

Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia

PubMed Central

Tokuriki, Shuko; Okuno, Takashi; Ohta, Genrei

2015-01-01

Objective. To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (BPD). Methods. Twenty-five infants born at <33 wk of gestational age or with a birth weight of <1,500 g were enrolled. CO-Hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nε-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. Receiver operating characteristic (ROC) analysis was used to compare the biomarkers' predictive values. Results. Compared with infants in the no-or-mild BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels during the early postnatal period and higher 8-OHdG levels between postnatal days 5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD, the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8 was higher than AUCs for the urinary markers. Conclusions. CO-Hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing BPD. PMID:26294808

Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia.

PubMed

Tokuriki, Shuko; Okuno, Takashi; Ohta, Genrei; Ohshima, Yusei

2015-01-01

To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (BPD). Twenty-five infants born at <33 wk of gestational age or with a birth weight of <1,500 g were enrolled. CO-Hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nε-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. Receiver operating characteristic (ROC) analysis was used to compare the biomarkers' predictive values. Compared with infants in the no-or-mild BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels during the early postnatal period and higher 8-OHdG levels between postnatal days 5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD, the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8 was higher than AUCs for the urinary markers. CO-Hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing BPD.

Long-term exposure to diesel engine exhaust induces primary DNA damage: a population-based study.

PubMed

Duan, Huawei; Jia, Xiaowei; Zhai, Qingfeng; Ma, Lu; Wang, Shan; Huang, Chuanfeng; Wang, Haisheng; Niu, Yong; Li, Xue; Dai, Yufei; Yu, Shanfa; Gao, Weimin; Chen, Wen; Zheng, Yuxin

2016-02-01

Diesel engine exhaust (DEE) is a ubiquitous environmental pollutant and is carcinogenic to humans. To seek early and sensitive biomarkers for prediction of adverse health effects, we analysed the components of DEE particles, and examined the genetic and oxidative damages in DEE-exposed workers. 101 male diesel engine testing workers who were constantly exposed to DEE and 106 matched controls were enrolled in the present study. The components of DEE were analysed, including fine particulate matter (PM2.5), element carbon (EC), nitrogen dioxide (NO2), sulfur dioxide (SO2) and polycyclic aromatic hydrocarbons (PAHs). Postshift urine samples were collected and analysed for 1-hydroxypyrene (1-OHP), an internal exposure marker for DEE. Levels of DNA strand breaks and oxidised purines, defined as formamidopyrimidine-DNA glycosylase (FPG) sites in leucocytes, were measured by medium throughput Comet assay. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also used to determine the level of oxidative stress. We found higher levels of PM2.5, EC, NO2, SO2 and PAHs in the diesel engine testing workshop and significantly higher urinary 1-OHP concentrations in exposed subjects (p<0.001). Compared with controls, the levels of parameters in normal Comet and FPG-Comet assay were all significantly higher in DEE-exposed workers (p<0.001), and in a dose-dependent and time-dependent manner. There were no significant differences between DEE-exposed workers and controls in regard to leucocyte FPG sensitive sites and urinary 8-OHdG levels. These findings suggest that DEE exposure mainly induces DNA damage, which might be used as an early biomarker for risk assessment of DEE exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico.

PubMed

Watkins, Deborah J; Ferguson, Kelly K; Anzalota Del Toro, Liza V; Alshawabkeh, Akram N; Cordero, José F; Meeker, John D

2015-03-01

Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α)) were measured twice during pregnancy (n=105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy (n=54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG (p=0.001) and 29% higher isoprostane (p=0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p<0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 (p=0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed. Copyright © 2014 Elsevier GmbH. All rights reserved.

Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico

PubMed Central

Watkins, Deborah J.; Ferguson, Kelly K.; Toro, Liza V. Anzalota Del; Alshawabkeh, Akram N.; Cordero, José F.; Meeker, John D.

2014-01-01

Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α)) were measured twice during pregnancy (n=105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy (n=54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG (p=0.001) and 29% higher isoprostane (p=0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p<0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 (p=0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed. PMID:25435060

The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours.

PubMed

Räsänen, J V; Sihvo, E I T; Ahotupa, M O; Färkkilä, M A; Salo, J A

2007-12-01

The most common marker of oxidative DNA damage is 8-hydroxydeoxyguanosine (8-OHdG), which is linked with several malignancies. In the present study we investigated whether DNA damage linked to oxidative stress (as 8-OHdG) is present in Barrett's mucosa with or without associated adenocarcinoma or high-grade dysplasia and in normal controls' squamous mucosa. We measured 8-OHdG in 51 patients (13 Barrett's metaplasia, six Barrett's oesophagus with high-grade dysplasia, 18 adenocarcinoma of the distal oesophagus/oesophagogastric junction and 14 normal controls). The amount of DNA damage was determined by high-performance liquid chromatography in oesophagus samples obtained either from endoscopy or as samples from surgery. The median 8-OHdG concentration was expressed as the ratio of 8-OHdG per 10(5) deoxyguanosine. Analysis revealed that 8-OHdG was present in both Barrett's metaplasia with and without dysplasia as well as in adenocarcinoma of the oesophagus/oesophagogastric junction. Although the study group was small the amount of 8-OHdG was significantly increased in the distal oesophagus both in Barrett's epithelium 1.26 (0.08-29.47) and in high-grade dysplasia 1.35 (1.04-1.65) as well as in adenocarcinoma of oesophagus/oesophagogastric junction 1.08 (0.59-1.94) compared to controls 0.06 (0-4.08) (p=0.002, p=0.012, p=0.001, respectively). Barrett's patients had no significant difference in 8-OHdG levels between their distal and proximal oesophageal samples. Our results show the presence of oxidative DNA damage in the distal oesophagus of patients with Barrett's oesophagus and adenocarcinoma of the oesophagus/oesophagogastric junction. This may have a connection to carcinogenesis in Barrett's oesophagus.

Biosensing of DNA oxidative damage: a model of using glucose meter for non-glucose biomarker detection.

PubMed

Zhu, Xuena; Sarwar, Mehenur; Yue, Qiaoli; Chen, Chunying; Li, Chen-Zhong

2017-01-01

Non-glucose biomarker-DNA oxidative damage biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been successfully detected using a smartphone-enabled glucose meter. Through a series of immune reactions and enzymatic reactions on a solid lateral flow platform, 8-OHdG concentration has been converted to a relative amount of glucose, and therefore can be detected by conventional glucose meter directly. The device was able to detect 8-OHdG concentrations in phosphate buffer saline as low as 1.73 ng mL -1 with a dynamic range of 1-200 ng mL -1 . Considering the inherent advantages of the personal glucose meter, the demonstration of this device, therefore, should provide new opportunities for the monitoring of a wide range of biomarkers and various target analytes in connection with different molecular recognition events.

PPARGC1A variation associated with DNA damage, diabetes, and cardiovascular diseases: the Boston Puerto Rican Health Study.

PubMed

Lai, Chao-Qiang; Tucker, Katherine L; Parnell, Laurence D; Adiconis, Xian; García-Bailo, Bibiana; Griffith, John; Meydani, Mohsen; Ordovás, José M

2008-04-01

Individuals with type 2 diabetes exhibit higher DNA damage and increased risk of cardiovascular disease (CVD). However, mechanisms underlying the association between DNA damage and development of type 2 diabetes and CVD are not understood. We sought to link peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A), a master transcriptional regulator of mitochondrial oxidative phosphorylation and cellular energy metabolism, with DNA damage, type 2 diabetes, and CVD. We measured DNA damage as urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and examined the relationship between nine PPARGC1A genetic variants, DNA damage, type 2 diabetes, and self-reported CVD in 959 participants of the Boston Puerto Rican Health Study. With respect to urinary 8-OHdG, PPARGC1A variants showed significant association, and PPARGC1A haplotypes exhibited significant association after correction for multiple testing. Two independent PPARGC1A variants associated significantly with type 2 diabetes (odds ratios [ORs] 1.35 and 2.46; P = 0.045 and <0.001). Carriers of minor alleles of two other PPARGC1A variants, both in strong linkage disequilibrium and associated with lower DNA damage, showed lower prevalence of CVD (ORs 0.53 and 0.65; P = 0.030 and 0.175). Moreover, we found that physical activity correlated negatively with DNA damage. It is plausible that low physical activity combined with risk haplotyes contribute to the high prevalence of type 2 diabetes in this population. We propose that PPARGC1A influences development of type 2 diabetes and CVD via DNA damage. Increasing physical activity, which induces PPARGC1A expression, is a potential strategy to slow DNA damage, thereby decreasing the risk of CVD for individuals with type 2 diabetes.

Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takata, Ayako; Yamauchi, Hiroshi, E-mail: hyama@kitasato-u.ac.jp; Toya, Tadao

Chrysotile (CH), the most common form of asbestos, is rendered less toxic by heating it at 1000 {sup o}C and converting it to forsterite (FO-1000). However, further safety tests are needed to evaluate human health risk of these materials. It has been reported that serum concentrations of megakaryocyte potentiating factor N-ERC/mesothelin become elevated in patients with mesotheliomas caused by asbestos exposure. In this study, a single 2 mg dose of CH or FO-1000 was intratracheally administered to rats. Within 180 days after the administrations, serum N-ERC/mesothelin concentrations, levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in lung tissues and pathological changes in respiratory organsmore » were determined. In the CH group, a significant increase in serum N-ERC/mesothelin concentrations was observed immediately after intratracheal administration, and the elevation lasted for 30 days. In lung tissues, positive staining for 8-OHdG in bronchioles, alveolar epithelium, inflammatory cells, and granulomas was evidence of a marked DNA oxidative damage. Furthermore, measurements of 8-OHdG in lung tissues based on the HPLC-ECD method suggested that serum N-ERC/mesothelin concentrations tended to increase when there are significant DNA damages in lung tissues. In contrast, in the FO-1000 group, a marked rise in serum N-ERC/mesothelin concentrations occurred only in the early phase (1-7 days) after intratracheal administration. Similarly, FO-1000 induced elevation of 8-OHdG in lung tissues was transient and modest compared with those of the CH-treated animals. In both the CH and FO-1000 groups, we observed significant correlations between serum N-ERC/mesothelin concentrations and lung 8-OHdG concentrations (r = 0.559, p = 0.001 for the CH group; r = 0.516, p = 0.01 for the FO-1000 group). In summary, we demonstrated the possibility of using serum N-ERC/mesothelin concentrations as a useful biomarker for early phase exposure to either CH or FO-1000.« less

Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention.

PubMed

Chen, L; Stacewicz-Sapuntzakis, M; Duncan, C; Sharifi, R; Ghosh, L; van Breemen, R; Ashton, D; Bowen, P E

2001-12-19

Human prostate tissues are vulnerable to oxidative DNA damage. The risk of prostate cancer is lower in men reporting higher consumption of tomato products, which contain high levels of the antioxidant lycopene. We examined the effects of consumption of tomato sauce-based pasta dishes on lycopene uptake, oxidative DNA damage, and prostate-specific antigen (PSA) levels in patients already diagnosed with prostate cancer. Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for the 3 weeks (30 mg of lycopene per day) preceding their scheduled radical prostatectomy. Serum and prostate lycopene concentrations, serum PSA levels, and leukocyte DNA oxidative damage (ratio of 8-hydroxy-2'-deoxyguanosine [8-OHdG] to 2'-deoxyguanosine [dG]) were assessed before and after the dietary intervention. DNA oxidative damage was assessed in resected prostate tissue from study participants and from seven randomly selected prostate cancer patients. All statistical tests were two-sided. After the dietary intervention, serum and prostate lycopene concentrations were statistically significantly increased, from 638 nM (95% confidence interval [CI] = 512 to 764 nM) to 1258 nM (95% CI = 1061 to 1455 nM) (P<.001) and from 0.28 nmol/g (95% CI = 0.18 to 0.37 nmol/g) to 0.82 nmol/g (95% CI = 0.57 to 1.11 nmol/g) (P <.001), respectively. Compared with preintervention levels, leukocyte oxidative DNA damage was statistically significantly reduced after the intervention, from 0.61 8-OHdG/10(5) dG (95% CI = 0.45 to 0.77 8-OHdG/10(5) dG) to 0.48 8-OHdG/ 10(5) dG (95% CI = 0.41 to 0.56 8-OHdG/10(5) dG) (P =.005). Furthermore, prostate tissue oxidative DNA damage was also statistically significantly lower in men who had the intervention (0.76 8-OHdG/10(5) dG [95% CI = 0.55 to 0.96 8-OHdG/10(5) dG]) than in the randomly selected patients (1.06 8-OHdG/10(5) dG [95% CI = 0.62 to 1.51 8-OHdG/10(5) dG]; P =.03). Serum PSA levels decreased after the intervention, from 10.9 ng/mL (95% CI = 8.7 to 13.2 ng/mL) to 8.7 ng/mL (95% CI = 6.8 to 10.6 ng/mL) (P<.001). These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.

Markers of Oxidative Stress in Human Milk do not Differ by Maternal BMI But are Related to Infant Growth Trajectories.

PubMed

Young, Bridget E; Patinkin, Zachary W; Pyle, Laura; de la Houssaye, Becky; Davidson, Barbara S; Geraghty, Sheela; Morrow, Ardythe L; Krebs, Nancy

2017-06-01

Objective Obesity in adults is associated with inflammation and oxidative stress. Whether or not this phenotype is reflected in human milk (HM) composition, or may impact infant growth remains unknown. We investigated whether HM from overweight/obese (OW/Ob) mothers exhibited higher concentrations of inflammatory cytokines and markers of oxidative stress. We also correlated these bioactive components with infant growth patterns. Methods This was an observational cohort of 56 breastfeeding mothers and their infants [33 normal weight (NW) and 23 OW/Ob]. Infants were followed until 6 months of age and HM collected at 2-weeks and 4-months. Results Markers of oxidative stress, 8-hydroxy-deoxyguanosine (8OHdG) and 4-hydroxynonenol (HNE), decreased in HM over time (p < 0.001) and did not differ between NW and OW/Ob women. Concentrations of inflammatory cytokines, IL-6, IL-8, and TNF-α, were all inter-correlated (p < 0.001) but did not differ between NW and OW/Ob women. HM fat, protein, lactose, and total calories did not differ between NW and OW/Ob women. Infant growth patterns did not differ by group. In a model of infant weight-for-length-Z score trajectory, there was a significant interaction between both lactose and 8OHdG with maternal group: HM lactose and 8OHdG concentrations were both positively associated with increases in WLZ trajectory only among infants breastfed by OW/Ob mothers. Conclusions for Practice HM composition was relatively stable between NW and OW/Ob women. In exclusively breastfed infants, HM concentrations of lactose and 8OHdG, a marker of oxidative stress, may contribute to regulation of infant weight gain, especially among infants of OW/Ob women.

Oxidative damage of DNA in subjects occupationally exposed to lead.

PubMed

Pawlas, Natalia; Olewińska, Elżbieta; Markiewicz-Górka, Iwona; Kozłowska, Agnieszka; Januszewska, Lidia; Lundh, Thomas; Januszewska, Ewa; Pawlas, Krystyna

2017-09-01

Exposure to lead (Pb) in environmental and occupational settings continues to be a serious public health problem and may pose an elevated risk of genetic damage. The aim of this study was to assess the level of oxidative stress and DNA damage in subjects occupationally exposed to lead. We studied a population of 78 male workers exposed to lead in a lead and zinc smelter and battery recycling plant and 38 men from a control group. Blood lead levels were detected by graphite furnace atomic absorption spectrophotometry and plasma lead levels by inductively coupled plasma-mass spectrometry. The following assays were performed to assess the DNA damage and oxidative stress: comet assay, determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation and total antioxidant status (TAS). The mean concentration of lead in the blood of the exposed group was 392 ± 103 μg/L and was significantly higher than in the control group (30.3 ± 29.4 μg/L, p < 0.0001). Oxidative DNA damages measured by comet assay showed no significant differences between populations. The concentration of 8-OHdG was about twice as high as in the control group. We found a significant positive correlation between the level of biomarkers of lead exposure [lead in blood, lead in plasma, zinc protoporphyrin (ZPP)] and urine concentration of 8-OHdG. The level of oxidative damage of DNA was positively correlated with the level of lipid peroxidation (TBARS) and negatively with total anti-oxidative status (TAS). Our study suggests that occupational exposure causes an increase in oxidative damage to DNA, even in subjects with relatively short length of service (average length of about 10 years). 8-OHdG concentration in the urine proved to be a sensitive and non-invasive marker of lead induced genotoxic damage.

The study of DNA adduct 8-hydroxy-2‧deoxyguanosine (8-OHdG) formation of butylated hydroxyanisole (BHA) and its metabolite ter-butyl hydroquinone (TBHQ) through in vitro reaction with Calf Thymus DNA and 2‧deoxyguanosine

NASA Astrophysics Data System (ADS)

Budiawan; Purwaningsih, S. S.; Cahaya, D. I.

2017-04-01

Butylated Hydroxyanisole (BHA) and its metabolite Tert-Butyl Hydroquinone (TBHQ) are synthetic antioxidants, commonly used as food and beverage preservatives. Although WHO declared their safety, the use of these preservatives are still controversial because some studies showed that BHA induced proliferative effects in animal testing and TBHQ is considered as carcinogenic and causes DNA cleavage. This study is aimed to analyze the interaction between Calf Thymus DNA with BHA and TBHQ which are mediated with Copper (II) Chloride. The result of the study in spectrophotometric showed there was bathochromic shift as much as 2-3 nm in DNA treated with TBHQ. The next analysis used HPLC method in stationary phase of ODS, mobile phase of 10mM Natrium Hydrogen Phosphate Buffer and Methanol (85 : 15) for DNA adduct formation, 8-Hydroxy-2-Deoxyguanosine (8-OHDG) as biomarker of risk cancer. The resultof the study showed the formation of DNA adduct 8-OHDG in the interaction between DNA and 20-500 ppm of TBHQ. The 8-OHdG formation was greatly increased by the higher concentration of TBHQ. The relative amount of 8 OHDG which formed was reached 946/105 deoxyguanosine in DNA bases. Confirmation test by LCMS/MS was characterized with the detection of mother ion peak (m/z 284); fragment ion peaks at m/z 167.9, and 139.9; at retention time 3.52 min. Meanwhile the interaction between DNA and 50-250 ppm BHA did not induce 8-OHDG.

Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

PubMed

Altemose, Brent; Robson, Mark G; Kipen, Howard M; Ohman Strickland, Pamela; Meng, Qingyu; Gong, Jicheng; Huang, Wei; Wang, Guangfa; Rich, David Q; Zhu, Tong; Zhang, Junfeng

2017-05-01

Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.

Neurotoxic responses in brain tissues of rainbow trout exposed to imidacloprid pesticide: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and acetylcholinesterase activity.

PubMed

Topal, Ahmet; Alak, Gonca; Ozkaraca, Mustafa; Yeltekin, Aslı Cilingir; Comaklı, Selim; Acıl, Gurdal; Kokturk, Mine; Atamanalp, Muhammed

2017-05-01

The extensive use of imidacloprid, a neonicotinoid insecticide, causes undesirable toxicity in non-targeted organisms including fish in aquatic environments. We investigated neurotoxic responses by observing 8-hydroxy-2-deoxyguanosine (8-OHdG) activity, oxidative stress and acetylcholinesterase (AChE) activity in rainbow trout brain tissue after 21 days of imidacloprid exposure at levels of (5 mg/L, 10 mg/L, 20 mg/L). The obtained results indicated that 8-OHdG activity did not change in fish exposed to 5 mg/L of imidacloprid, but 10 mg/L and 20 mg/L of imidacloprid significantly increased 8-OHdG activity compared to the control (p < 0.05). An immunopositiv reaction to 8-OHdG was detected in brain tissues. The brain tissues indicated a significant increase in antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) compared to the control and there was a significant increase in malondialdehyde (MDA) levels (p < 0.05). High concentrations of imidacloprid caused a significant decrease in AChE enzyme activity (p < 0.05). These results suggested that imidacloprid can be neurotoxic to fish by promoting AChE inhibition, an increase in 8-OHdG activity and changes in oxidative stress parameters. Therefore, these data may reflect one of the molecular pathways that play a role in imidacloprid toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress.

PubMed

Loeffler, David A; Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

2016-01-01

Age-associated declines in protein homeostasis mechanisms ("proteostasis") are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = -0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = -0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: -0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain.

Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress

PubMed Central

Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.; LeWitt, Peter A.

2016-01-01

Age-associated declines in protein homeostasis mechanisms (“proteostasis”) are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = –0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = –0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: –0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain. PMID:27507943

DNA oxidative damage and life expectancy in houseflies.

PubMed Central

Agarwal, S; Sohal, R S

1994-01-01

The objective of this study was to explore the relationship between oxidative molecular damage and the aging process by determining whether such damage is associated with the rate of aging, using the adult housefly as the experimental organism. Because the somatic tissues in the housefly consist of long-lived postmitotic cells, it provides an excellent model system for studying cumulative age-related cellular alterations. Rate of aging in the housefly was manipulated by varying the rate of metabolism (physical activity). The concentration of 8-hydroxydeoxyguanosine (80HdG) was used as an indicator of DNA oxidation. Exposure of live flies to x-rays and hyperoxia elevated the level of 8OHdG. The level of 8OHdG in mitochondrial as well as total DNA increased with the age of flies. Mitochondrial DNA was 3 times more susceptible to age-related oxidative damage than nuclear DNA. A decrease in the level of physical activity of the flies was found to prolong the life-span and corresponding reduce the level of 8OHdG in both mitochondrial and total DNA. Under all conditions examined, mitochondrial DNA exhibited a higher level of oxidative damage than total DNA. The 8OHdG levels were found to be inversely associated with the life expectancy of houseflies. The pattern of age-associated accrural of 8OHdG was virtually identical to that of protein carbonyl content. Altoghether, results of this study support the hypothesis that oxidative molecular damage is a causal factor in senescence. PMID:7991627

Effects of a supplement combining Pycnogenol® and l-arginine aspartate on lower urinary dysfunction compared with saw palmetto extract.

PubMed

Yagi, Hiroshi; Sato, Ryo; Nishio, Kojiro; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

2017-01-01

Lower urinary tract symptoms (LUTS) and sexual dysfunction (SDys) are common problems that affect quality of life (QOL) in elderly men. In addition to prescribed drugs, many over-the-counter medications including supplements are used to treat QOL diseases. Phosphodiesterase inhibitors are reported to be effective for both LUTS and SDys by increasing nitric oxide levels. French maritime pine bark extract Pycnogenol ® , which is a potent nitric oxide donor, is reported to be effective for SDys. However, no reports have been published on whether it ameliorates LUTS. Open-labeled, randomized study. The effects of two supplements, Nokogiriyashi EX ® containing 160 mg saw palmetto (SP) extract per tablet and Edicare ® containing 10 mg of Pycnogenol ® , 115 mg of l-arginine and 92 mg of aspartate (PAA) per tablet on International Prostate Symptom Score (IPSS), IPSS-QOL, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), urinary 8-OHdG and uroflowmetry (UFM) of total 40 men with LUTS and SDys were examined. 19 subjects were instructed to take two tablets of SP, on the other 20 were on four tablets of PAA for 16 weeks. IPSS and IPSS-QOL showed statistically significant improvements in both groups. OABSS and IIEF5 were significantly improved in the PAA group. Conversely, ICIQ-SF, 8-OHdG and UFM did not change in either group. PAA might be an effective therapeutic alternative for elderly patients with LUTS and SDys.

A longitudinal study of atrazine and 2,4-D exposure and oxidative stress markers among Iowa corn farmers

PubMed Central

Lerro, Catherine C.; Beane Freeman, Laura E.; Portengen, Lützen; Kang, Daehee; Lee, Kyoungho; Blair, Aaron; Lynch, Charles F.; Bakke, Berit; De Roos, Anneclaire J.; Vermeulen, Roel C.H.

2018-01-01

Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism’s antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. We utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40–60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F2α [8-isoPGF]) were measured in urine. We calculated β estimates and 95% confidence intervals (95%CI) for each pesticide-oxidative stress marker combination using multivariate linear mixed-effect models for repeated measures. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared to controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β=0.066, 95%CI=0.008–0.124) and 8-isoPGF (β=0.088, 95%CI=0.004–0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases. PMID:28116766

Biomarkers of PAH exposure and hematologic effects in subjects exposed to combustion emission during residential (and professional) cooking practices in Pakistan.

PubMed

Kamal, Atif; Cincinelli, Alessandra; Martellini, Tania; Malik, Riffat Naseem

2016-01-01

The aim of this study was to evaluate and compare the exposure of household women and professional male workers to combustion emission in the indoor and semi-outdoor environments, respectively, by using biochemical parameters and the biomarkers of exposure to polycyclic aromatic hydrocarbon (PAH). Female (WR n = 60) and male "cooks" (WC n = 60) exposed to the combustion emission of fuel wood and coal in rural/suburban areas of Pakistan were recruited in this study and compared to non-exposed female (CF) and male (CM) groups (n = 32 and 34, respectively). Urinary biomarkers of PAH exposure including 1-hyroxypyrene (1-OHPyr), α-naphthol, and β-naphthol were analyzed together with the biomarkers of effect, including the serum c-reactive proteins (CRP), white blood cells (WBCs), hemoglobin (Hb), red blood cells (RBC), and platelet (PLT) count. In addition, blood superoxide dismutase (SOD) and urinary level of 8-hydroxydeoxyguanosine (8-OHdG) were evaluated to determine the oxidative stress and DNA damage, respectively. A questionnaire was used to document demographic-, health-, and exposure-related information. The results showed that urinary β-naphthol was almost 44% higher in WR subjects than WC (median 7.69 vs. 3.39 μmol/mol-Cr, respectively; p = 0.01) and respective controls (CF). Higher urinary 8-OHdG were observed in WR (71.1 ng/mg-Cr) than WC (56.37 ng/mg-Cr) (p < 0.001), and lower life status and higher degree of headache were observed in WR than WC. In WCs, however, a low Hb and high WBC (8.29 × 10(3) μL(-1), ranging between 6.1 and 10.6 × 10(3) μL(-1)) were observed in comparison with CM. The study shows that WC subjects used larger amount of fuel and were subjected to prolonged exposure. It was concluded that the role of ventilation is fundamental and WR were more exposed to PAHs despite the fact that WC spent more time in cooking (due to occupational requirement) than WR.

Induction of oxidative DNA damage in anaerobes.

PubMed

Takeuchi, T; Nakaya, Y; Kato, N; Watanabe, K; Morimoto, K

1999-05-07

We compared oxidative DNA damage in strictly anaerobic Prevotella melaninogenica, aerotolerant anaerobic Bacteroides fragilis, and facultative anaerobic Salmonella typhimurium after exposure to O2 or H2O2. Using HPLC with electrochemical detection, we measured 8-hydroxydeoxyguanosine (8OHdG) as a damage marker. O2 induced 8OHdG in P. melaninogenica but not in B. fragilis, which shows catalase activity, or in S. typhimurium. In P. melaninogenica, with catalase, O2 induced less 8OHdG; superoxide dismutase had no effect; with glucose and glucose oxidase, O2 induced more 8OHdG. H2O2 also markedly increased 8OHdG. O2 was suggested to induce 8OHdG through H2O2. O2 or H2O2 decreased survival only in P. melaninogenica. Highly sensitive to oxidative stress, P. melaninogenica could prove useful for investigating oxidative DNA damage.

Evaluation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct levels and DNA strand breaks in human peripheral blood lymphocytes exposed in vitro to polycyclic aromatic hydrocarbons with or without animal metabolic activation.

PubMed

Isabel, Rodríguez-Romero María; Sandra, Gómez-Arroyo; Rafael, Villalobos-Pietrini; Carmen, Martínez-Valenzuela; Josefina, Cortés-Eslava; del Carmen, Calderón-Ezquerro María; Rocío, García-Martínez; Francisco, Arenas-Huertero; Elena, Calderón-Segura María

2012-04-01

The polycyclic aromatic hydrocarbons (PAHs) dibenzo(a,h)anthracene, benzo(ghi)perylene, benzo(b)fluoranthene and benzo(a)pyrene have been identified in urban air from Mexico City and some of them are classified as human carcinogens. In the present study, human peripheral blood lymphocytes were exposed in vitro to different concentrations of PAHs with (+S9) or without (-S9) metabolic activation. The genotoxic and cytotoxic effects of each PAH were examined with an alkaline comet assay and trypan blue dye exclusion, and oxidative DNA damage was determined via the detection of 8-hydroxy-2'-deoxyguanosine (8-OhdG) adduct levels by enzyme-linked immunosorbent assay (ELISA). The DNA damage was evaluated with two genotoxicity parameters: the frequency of comets and the comet tail length. Concentrations of 20, 40, 80, 160 and 320 µM DB(a,h)A-S9; 20, 40, 80, 160 and 240 µM B(ghi)P-S9; 20, 30, 40, 60 and 80 µM B(b)F-S9; and 80 µM B(a)P-S9 for 24 h induced a small but significant increase in the means of comet frequency, in the tail length and in the 8-oHDg levels in relation to the control (0.5% DMSO-S9). However, all PAHs+S9 produced a more significant increase in DNA strand breaks and the level of 8-OHdG compared with the control (0.5% DMSO+S9), with a concentration-effect relationship. The viability of lymphocytes exposed to all PAHs-S9 and PAHs+S9 was not modified compared with the control. The results of this study demonstrate that the comet and ELISA are rapid, suitable and sensitive methods to detect in vitro PAH-induced DNA damage in human peripheral lymphocytes.

DNA damage in children with obstructive adenotonsillar hypertrophy.

PubMed

Yoruk, Ozgur; Alp, Hakan; Yuksel, Sancak; Bakan, Ebubekir

2014-11-01

The objective of this prospective, controlled study was to evaluate oxidative DNA damage in children with obstructive adenotonsillar hypertrophy. This study included 30 patients with obstructive adenotonsillar hypertrophy (male/female ratio, 3:2; age range, 3-9 y) scheduled to undergo tonsillectomy and adenoidectomy and 25 control subjects of similar age and sex with no adenotonsillar disease or airway obstruction. Urine and blood samples were obtained from each child for 8-hydroxy 2-deoxyguanosine (8-OhdG) and malondialdehyde (MDA) concentrations. There were significant differences in leukocyte (3.28 [0.69/10] vs 0.70 [0.15/10] dG) and urine 8-OhdG (8.22 [2.27/10] vs 5.26 [1.3/10] dG) levels in patients with obstructive adenotonsillar hypertrophy and healthy subjects (P < 0.001 for both). Plasma (2.98 [1.31] vs 1.14 [0.64] μM) and urine (1.77 [0.84] vs 0.56 [0.32] μM) MDA levels were also different (P < 0.001 for both). There were positive correlations between 8-OhdG in leukocyte DNA and plasma MDA (r = 0.648, P < 0.001) and between levels of urine 8-OhdG excretion and urine MDA (r = 0.588, P < 0.001). The DNA damage in children with adenotonsillar hypertrophy should be kept in mind, but further studies must be done with larger patient groups.

Serum 8-OHdG and HIF-1α levels: do they affect the development of malignancy in patients with hypoactive thyroid nodules?

PubMed

Ece, Harman; Mehmet, Erdogan; Cigir, Biray Avci; Yavuz, Dodurga; Muammer, Karadeniz; Cumhur, Gunduz; Mustafa, Harman; Sevki, Cetinkalp; Fusun, Saygılı; Gokhan, Ozgen Ahmet

2013-01-01

This study aimed to evaluate 8-OHdG and hypoxia-inducible factor 1 (HIF-1α) levels in patients with hypoactive thyroid nodules (toxic multi-nodular goiter, Graves' disease, and Hashimoto's thyroiditis), as these parameters may be related to oxidative stress and the pathogenesis of cancer. The study included patients diagnosed with Graves' disease (n = 20), toxic multinodular goiter (n = 20), and Hashimoto thyroiditis (n = 20), and 20 healthy controls. HIF-1α levels were measured in blood samples and 8-OHdG levels were measured in urine - both via ELISA. HIF-1α and 8-OHdG levels were significantly higher in the patient groups than in the control group (p < 0.05). In the Hashimoto's thyroiditis patients a correlation was observed between 8-OHdG and thyroglobulin antibodies (p = 0.03). A significant relation was found between 8-OHdG and HIF-1α in the patient group (p < 0.01). Carcinoma was detected in 7 of 43 female patients, but not in any of the male patients. No difference was observed in 8-OHdG or HIF-1α levels between the patients with and without papillary carcinoma (p > 0.05). There was no significant difference in 8-OHdG or HIF-1α levels between the patients with biopsy results that were benign, malignant, and non-diagnostic (p > 0.05). Serum HIF-1α and urine 8-OHdG levels were significantly higher in the patients with thyroid diseases; however, a relationship with cancer was not observed.

Synthetic 8-hydroxydeoxyguanosine inhibited metastasis of pancreatic cancer through concerted inhibitions of ERM and Rho-GTPase.

PubMed

Park, Jong-Min; Han, Young-Min; Jeong, Migyeong; Chung, Myung Hee; Kwon, Chang Il; Ko, Kwang Hyun; Hahm, Ki Baik

2017-09-01

8-hydroxydeoxyguanosine (8-OHdG) is generated consequent to oxidative stress, but its paradoxical anti-oxidative, anti-inflammatory, and anti-mutagenic effects via Rho-GTPase inhibition were noted in various models of inflammation and cancer. Metastasis occurs through cell detachment, epithelial-mesenchymal transition (EMT), and cell migration; during these processes, changes in cell morphology are initiated through Rho-GTPase-dependent actin cytoskeleton polymerization. In this study, we explored the anti-metastatic mechanisms of 8-OHdG in Panc-1 pancreatic cancer cells. 8-OHdG inhibits cell migration by inactivating ERM and Rho-GTPase proteins, and inhibiting focal adhesion kinase (FAK) and matrix metalloproteinases (MMPs). At 15min, 8-OHdG significantly inactivated ERM (p < 0.05) and led to a significant retardation of wound healing; siERM and H1152 (ROCK inhibitor) had similar effects (p < 0.05). However, FAK inhibitor 14, DPI (NOX inhibitor), and NAC (antioxidant) significantly delayed wound healing without inhibiting ERM or CD44 (p < 0.05). In the experiments on cell migration, siERM, siCD44, DPI, and 8-OHdG significantly inhibited MMPs. 8-OHdG significantly decreased DCF-DA activation in Panc-1 pancreatic cancer cells and down-regulated NOXs (nox-1, nox-2, and nox-3). Finally, all of these anti-migration actions of 8-OHdG resulted in significant inhibition of EMT, as evidenced by the up-regulation of ZO-1 and claudin-1 and down-regulation of vimentin. We found significant inhibition of lung metastasis of Panc-1 cells by 8-OHdG. In conclusion, exogenous 8-OHdG had potent anti-metastasis effects mediated by either ERM or Rho GTPase inhibition in metastasis-prone pancreatic cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Exposure to polycyclic aromatic hydrocarbons and volatile organic compounds among recently pregnant rural Guatemalan women cooking and heating with solid fuels.

PubMed

Weinstein, John R; Asteria-Peñaloza, Renée; Diaz-Artiga, Anaité; Davila, Gilberto; Hammond, S Katharine; Ryde, Ian T; Meyer, Joel N; Benowitz, Neal; Thompson, Lisa M

2017-06-01

Household air pollution is a major contributor to death and disability worldwide. Over 95% of rural Guatemalan households use woodstoves for cooking or heating. Woodsmoke contains carcinogenic or fetotoxic polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Increased PAHs and VOCs have been shown to increase levels of oxidative stress. We examined PAH and VOC exposures among recently pregnant rural Guatemalan women exposed to woodsmoke and compared exposures to levels seen occupationally or among smokers. Urine was collected from 23 women who were 3 months post-partum three times over 72h: morning (fasting), after lunch, and following dinner or use of wood-fired traditional sauna baths (samples=68). Creatinine-adjusted urinary concentrations of metabolites of four PAHs and eight VOCs were analyzed by liquid chromatography-mass spectrometry. Creatinine-adjusted urinary biomarkers of oxidative stress, 8-isoprostane and 8-OHdG, were analyzed using enzyme-linked immunosorbent assays (ELISA). Long-term (pregnancy through 3 months prenatal) exposure to particulate matter and airborne PAHs were measured. Women using wood-fueled chimney stoves are exposed to high levels of particulate matter (median 48h PM 2.5 105.7μg/m 3 ; inter-quartile range (IQR): 77.6-130.4). Urinary PAH and VOC metabolites were significantly associated with woodsmoke exposures: 2-naphthol (median (IQR) in ng/mg creatinine: 295.9 (74.4-430.9) after sauna versus 23.9 (17.1-49.5) fasting; and acrolein: 571.7 (429.3-1040.7) after sauna versus 268.0 (178.3-398.6) fasting. Urinary PAH (total PAH: ρ=0.89, p<0.001) and VOC metabolites of benzene (ρ=0.80, p<0.001) and acrylonitrile (ρ=0.59, p<0.05) were strongly correlated with long-term exposure to particulate matter. However urinary biomarkers of oxidative stress were not correlated with particulate matter (ρ=0.01 to 0.05, p>0.85) or PAH and VOC biomarkers (ρ=-0.20 to 0.38, p>0.07). Urinary metabolite concentrations were significantly greater than those of heavy smokers (mean cigarettes/day=18) across all PAHs. In 15 (65%) women, maximum 1-hydroxypyrene concentrations exceeded the occupational exposure limit of coke-oven workers. The high concentrations of urinary PAH and VOC metabolites among recently pregnant women is alarming given the detrimental fetal and neonatal effects of prenatal PAH exposure. As most women used chimney woodstoves, cleaner fuels are critically needed to reduce smoke exposure. Copyright © 2017 Elsevier GmbH. All rights reserved.

Late-intervention study with ebselen in an experimental model of type 1 diabetic nephropathy.

PubMed

Tan, S M; Sharma, A; Stefanovic, N; de Haan, J B

2015-03-01

Previous studies have shown that preventive treatment with the antioxidant, ebselen, in experimental models of type 1 diabetic nephropathy resulted in an attenuation of structural and functional damage in the kidney. However, evidence for the effectiveness of ebselen in late-intervention studies is lacking. Thus, we aimed to investigate the effects of ebselen in attenuating established renal injury in type 1 diabetic nephropathy using the Akita mouse model. Baseline blood glucose and albumin-to-creatinine ratio (ACR) were measured in wild-type (WT) and heterozygous Akita mice at 9 weeks of age. At 10 weeks of age, WT and Akita mice were randomized to receive either vehicle (5% carboxymethyl cellulose) or ebselen by oral gavage at 10mg/kg twice daily. Kidney and urine were collected after 16 weeks of treatment with ebselen for histological and functional analyses. At 9 weeks of age, Akita mice displayed well-established renal dysfunction with significant increases in ACR and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels when compared with WT controls. After 16 weeks of treatment with ebselen, oxidative stress, as measured by nitrotyrosine immunostaining and urinary 8-OHdG levels, was significantly reduced in the Akita mice. Furthermore, gene expression of the major reactive oxygen species-producing nicotinamide adenine dinucleotide phosphate enzyme, Nox4, was also reduced by ebselen. However, ebselen had no effect on ACR and glomerulosclerosis. Chronic treatment with ebselen significantly reduced oxidative stress in the Akita mice. However, ebselen failed to attenuate functional or structural kidney damage in this late-intervention study using the Akita mouse model.

Increased blood 8-hydroxy-2-deoxyguanosine levels in methamphetamine users during early abstinence.

PubMed

Huang, Ming-Chyi; Lai, Ying-Ching; Lin, Shih-Ku; Chen, Chun-Hsin

2018-01-01

Reactive oxygen species (ROS) are thought to play a role in the adverse physical and mental consequences of methamphetamine usage. The oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker of ROS-induced DNA damage. Currently, there is insufficient clinical information about methamphetamine-induced oxidative DNA damage. This study examined differences in blood levels of 8-OHdG between methamphetamine users and non-users as well as alterations in 8-OHdG levels after 2 weeks of methamphetamine abstinence. We recruited 182 methamphetamine users (78.6% of male) and 71 healthy controls (95.8% of male). Baseline serum 8-OHdG levels were measured in both groups using a competitive enzyme-linked immunosorbent assay. In methamphetamine users, 8-OHdG levels were measured again 2 weeks after baseline measurement. The results showed that methamphetamine users had significantly higher 8-OHdG levels (0.34 ± 0.13 ng/mL) than healthy controls (0.30 ± 0.08 ng/mL) (p < 0.001). The 8-OHdG levels did not alter after 2 weeks of methamphetamine abstinence (0.32 ± 0.12 ng/mL, p = 0.051 compared to baseline measurement; p = 0.12 compared to healthy controls). No significant correlations were observed between baseline 8-OHdG levels in methamphetamine users and post-abstinence interval, age of the first methamphetamine use, duration of methamphetamine use, or history of frequent methamphetamine use. Our findings suggest that methamphetamine users had an enhanced level of oxidative damage, which did not normalize during early abstinence. Future studies are required to determine the effects of long-term methamphetamine abstinence and potential confounders on 8-OHdG levels in methamphetamine users.

Effect of diesel exhaust inhalation on antioxidant and oxidative stress responses in adults with metabolic syndrome

PubMed Central

Allen, Jason; Trenga, Carol A.; Peretz, Alon; Sullivan, Jeffrey H.; Carlsten, Christopher C.; Kaufman, Joel D.

2011-01-01

Background Traffic-related air pollution is associated with cardiovascular morbidity and mortality. Although the biological mechanisms are not well understood, oxidative stress may be a primary pathway. Subpopulations, such as individuals with metabolic syndrome (MeS), may be at increased risk of adverse effects associated with air pollution. Our aim was to assess the relationship between exposure to diesel exhaust (DE) and indicators of systemic antioxidant and oxidative responses in adults with MeS. We hypothesized that DE exposure would result in greater oxidative stress and antioxidant responses compared with filtered air (FA). Methods Ten adult subjects with MeS were exposed on separate days for two hours to FA or DE (at 200μg/m3), in a double blind, crossover experiment. Urinary 8-isoPGF2α (F2-isoprostanes), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were assessed as markers of oxidative stress at 3 hrs and 22 hrs, respectively, after exposure initiation. To assess the short-term antioxidant response we analyzed plasma ascorbic acid (AA) 90 minutes after exposure initiation. All outcomes were compared to pre-exposure levels, and mean changes were compared between FA and DE exposures. Results Mean changes in urinary F2-isoprostanes (ng/mg creatinine), (-0.05 [95% CI = −0.29, 0.15]), and 8-OHdG (μg/g creatinine) (-0.09 [-0.13, 0.31]), were not statistically significant. Mean changes in plasma AA (mg/dl) were also not significant (-0.02 [-0.78, 0.04]). Conclusions In this carefully controlled experiment, we did not detect significant changes in oxidative stress or systemic antioxidant responses in subjects with MeS exposed to 200μg/m3 DE. PMID:19852547

Age-dependent systemic DNA damage in early Type 2 Diabetes mellitus.

PubMed

Rogulj, Dinko; El Aklouk, Ismail; Konjevoda, Paško; Ljubić, Spomenka; Pibernik Okanović, Mirjana; Barbir, Ante; Luburić, Marijana; Radman, Maja; Budinski, Ninoslav; Vučić Lovrenčić, Marijana

2017-01-01

Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM. Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, gamma-glutamyl transpeptidase (GGT), uric acid, C-reactive protein (CRP), total leukocyte/neutrophil count, and urinary 8-hidroxy-deoxyguanosine (u-8-OHdG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications. BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-OHdG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Higher 8-OHdG in older subjects with T2DM suggests that both aging process and diabetes could contribute to the development of DNA damage. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

Association between periodontitis and salivary 8-hydroxydeoxyguanosine among Korean rural adults.

PubMed

Shin, Myung-Seop; Shin, Hye-Sun; Ahn, Yoo-Been; Kim, Hyun-Duck

2016-08-01

This study aimed to evaluate the association between salivary 8-hydroxydeoxyguanosine (8-OHdG) and periodontitis among community-dwelling Korean adults. A total of 211 adults (80 men and 131 women) were cross-sectionally surveyed from the Sunchang Longevity Cohort. Periodontitis was defined as having at least 30% of teeth with proximal attachment loss ≥5 mm. The salivary 8-OHdG level was categorized into tertiles: low (<0.916 ng/ml), medium (0.916 to <2.675 ng/ml) and high (≥2.675 ng/ml). Sociodemographic, habitual and systemic health-related factors were controlled for. Logistic regression analysis was performed for the outcome of severe periodontitis. Analysis of covariance in general linear model was performed for the outcome of 8-OHdG. The high 8-OHdG level showed a significant association with periodontitis. The odds ratio (95% confidence interval) was 2.40 (1.05-5.51), and it was highlighted by adding the interaction term with drinking and smoking. The adjusted mean log-transformed value of 8-OHdG was significantly higher in the severe periodontitis group (1.40 ng/ml) than in the control group (1.02 ng/ml) (ancova, P = 0.028). 8-OHdG was associated with periodontitis. Thus, salivary 8-OHdG could be a useful marker for periodontitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Estimation of tissue and crevicular fluid oxidative stress marker in premenopausal, perimenopausal and postmenopausal women with chronic periodontitis.

PubMed

Chandra, Rampalli Viswa; Sailaja, Sistla; Reddy, Aileni Amarender

2017-09-01

The aim of this study was to estimate tissue and gingival crevicular fluid (GCF) levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in premenopausal, perimenopausal and postmenopausal women with chronic periodontitis. Oxidative stress has been implicated in the etiopathogenesis of periodontitis and menopause induces oxidative stress. According to Stages of Reproductive Aging Workshop (STRAW) criteria, women diagnosed with periodontitis were subdivided into three groups of 31 participants each 1. Premenopausal 2. Perimenopausal and 3. Postmenopausal. GCF and gingival tissue samples were collected from sites with maximum probing depth. Tissue DNA was extracted from the gingival sample and 8-OHdG in the extracted DNA, and GCF samples were measured using ELISA. There was a highly significant difference in the overall GCF 8-OHdG levels among the three groups with the pairwise difference being highly significant between the premenopausal-postmenopausal groups and perimenopausal-postmenopausal groups. However, no overall significant differences in tissue 8-OHdG levels were found among the three groups. Pairwise, highly significant differences were found between the premenopausal-postmenopausal groups and perimenopausal-postmenopausal groups for tissue 8-OHdG levels. No significant correlations were found between various measure of periodontal disease and GCF/tissue 8-OHdG levels among all the groups. Premenopausal-postmenopausal and perimenopausal-postmenopausal transition resulted in significant increase in tissue and GCF 8-OHdG levels. However, no association was found between stages of reproductive ageing and tissue levels of 8-OHdG. © 2017 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Phototherapy with blue and green mixed-light is as effective against unconjugated jaundice as blue light and reduces oxidative stress in the Gunn rat model.

PubMed

Uchida, Yumiko; Morimoto, Yukihiro; Uchiike, Takao; Kamamoto, Tomoyuki; Hayashi, Tamaki; Arai, Ikuyo; Nishikubo, Toshiya; Takahashi, Yukihiro

2015-07-01

Phototherapy using blue light-emitting diodes (LED) is effective against neonatal jaundice. However, green light phototherapy also reduces unconjugated jaundice. We aimed to determine whether mixed blue and green light can relieve jaundice with minimal oxidative stress as effectively as either blue or green light alone in a rat model. Gunn rats were exposed to phototherapy with blue (420-520 nm), filtered blue (FB; 440-520 nm without<440-nm wavelengths, FB50 (half the irradiance of filtered blue), mixed (filtered 50% blue and 50% green), and green (490-590 nm) LED irradiation for 24h. The effects of phototherapy are expressed as ratios of serum total (TB) and unbound (UB) bilirubin before and after exposure to each LED. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by HPLC before and after exposure to each LED to determine photo-oxidative stress. Values < 1.00 indicate effective phototherapy. The ratios of TB and UB were decreased to 0.85, 0.89, 1.07, 0.90, and 1.04, and 0.85, 0.94, 0.93, 0.89, and 1.09 after exposure to blue, filtered blue, FB50, and filtered blue mixed with green LED, respectively. In contrast, urinary 8-OHdG increased to 2.03, 1.25, 0.96, 1.36, 1.31, and 1.23 after exposure to blue, filtered blue, FB50, mixed, green LED, and control, indicating side-effects (> 1.00), respectively. Blue plus green phototherapy is as effective as blue phototherapy and it attenuates irradiation-induced oxidative stress. Combined blue and green spectra might be effective against neonatal hyperbilirubinemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antioxidant nutrients in plasma of Japanese patients with chronic obstructive pulmonary disease, asthma-COPD overlap syndrome and bronchial asthma.

PubMed

Kodama, Yuzo; Kishimoto, Yuki; Muramatsu, Yoko; Tatebe, Junko; Yamamoto, Yu; Hirota, Nao; Itoigawa, Yukinari; Atsuta, Ryo; Koike, Kengo; Sato, Tadashi; Aizawa, Koich; Takahashi, Kazuhisa; Morita, Toshisuke; Homma, Sakae; Seyama, Kuniaki; Ishigami, Akihito

2017-11-01

Few studies to date have investigated the antioxidant nutrients such as vitamin C (ascorbic acid), vitamin E (α-tocopherol), retinol and carotenoids in plasma from patients with pulmonary disease in Japan. To clarify the role of antioxidant nutrients such as vitamin C, vitamin E, retinol and various carotenoids in plasma of Japanese patients with chronic obstructive lung diseases (COPD), asthma-COPD overlap syndrome (ACOS) and/or bronchial asthma (BA), we compared to healthy elderly controls. Ascorbic acid (AA), carotenoids (lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene and lycopene), retinol and α-tocopherol levels in plasma were determined by using a high performance liquid chromatography. Reduced glutathione (GSH), oxidised glutathione (GSSG) in whole blood and urinary 8-OHdG were also determined. Plasma AA level of COPD subjects was significantly lower than that of healthy elderly people. Conversely, ACOS and BA subjects showed no significant difference from healthy elderly people. Moreover, plasma lycopene and total carotenoid levels and GSH content in blood were significantly lower in COPD subjects than these in healthy elderly people. However, other redox markers such as GSSG, GSH/GSSG ratio and urinary 8-OHdG found no significant differences between COPD, ACOS and BA compared to healthy elderly people. These results suggested that COPD of Japanese patients may develop partly because of oxidative stress derived from a shortage of antioxidant nutrients, especially of AA and lycopene, as well as GSH while this may not be the case in both ACOS and BA. © 2016 John Wiley & Sons Ltd.

The comparison of in vivo antigenotoxic and antioxidative capacity of two propylene glycol extracts of Calendula officinalis (marigold) and vitamin E in young growing pigs.

PubMed

Frankic, T; Salobir, K; Salobir, J

2009-12-01

The objective of the study was to evaluate the protective effect of Calendula officinalis propylene glycol extracts against oxidative DNA damage and lipid peroxidation induced by high polyunsaturated fatty acid (PUFA) intake in young growing pigs. Forty young growing pigs were assigned to five treatment groups: control; oil (linseed oil supplementation); C. officinalis 1 and 2 groups (linseed oil plus 3 ml/day of C. officinalis propylene glycol extracts); and vitamin E group (linseed oil plus 100 mg/kg of vitamin E). Lymphocyte DNA fragmentation and 24-h urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion were measured to determine DNA damage. Lipid peroxidation was studied by analysing plasma and urine malondialdehyde (MDA), and urine isoprostane concentrations (iPF2α-VI), total antioxidant status of plasma and glutathione peroxidase (GPx) assays. C. officinalis 1 (extract from petals) effectively protected DNA from oxidative damage. It indicated a numerical trend towards the reduction of plasma MDA and urinary iPF2α-VI excretion. Its effect was comparable with that of vitamin E. C. officinalis 2 (extract from flower tops) showed less antioxidant potential than the extract from petals. We can conclude that the amount of C. officinalis extracts proposed for internal use by traditional medicine protects the organism against DNA damage induced by high PUFA intake.

Blood concentrations of lead, cadmium, mercury and their association with biomarkers of DNA oxidative damage in preschool children living in an e-waste recycling area.

PubMed

Xu, Xijin; Liao, Weitang; Lin, Yucong; Dai, Yifeng; Shi, Zhihua; Huo, Xia

2017-06-16

Reactive oxygen species (ROS)-induced DNA damage occurs in heavy metal exposure, but the simultaneous effect on DNA repair is unknown. We investigated the influence of co-exposure of lead (Pb), cadmium (Cd), and mercury (Hg) on 8-hydroxydeoxyguanosine (8-OHdG) and human repair enzyme 8-oxoguanine DNA glycosylase (hOGG1) mRNA levels in exposed children to evaluate the imbalance of DNA damage and repair. Children within the age range of 3-6 years from a primitive electronic waste (e-waste) recycling town were chosen as participants to represent a heavy metal-exposed population. 8-OHdG in the children's urine was assessed for heavy metal-induced oxidative effects, and the hOGG1 mRNA level in their blood represented the DNA repair ability of the children. Among the children surveyed, 88.14% (104/118) had a blood Pb level >5 μg/dL, 22.03% (26/118) had a blood Cd level >1 μg/dL, and 62.11% (59/95) had a blood Hg level >10 μg/dL. Having an e-waste workshop near the house was a risk factor contributing to high blood Pb (r s  = 0.273, p < 0.01), while Cd and Hg exposure could have come from other contaminant sources. Preschool children of fathers who had a college or university education had significantly lower 8-OHdG levels (median 242.76 ng/g creatinine, range 154.62-407.79 ng/g creatinine) than did children of fathers who had less education (p = 0.035). However, we did not observe a significant difference in the mRNA expression levels of hOGG1 between the different variables. Compared with children having low lead exposure (quartile 1), the children with high Pb exposure (quartiles 2, 3, and 4) had significantly higher 8-OHdG levels (β Q2  = 0.362, 95% CI 0.111-0.542; β Q3  = 0.347, 95% CI 0.103-0.531; β Q4  = 0.314, 95% CI 0.087-0.557). Associations between blood Hg levels and 8-OHdG were less apparent. Compared with low levels of blood Hg (quartile 1), elevated blood Hg levels (quartile 2) were associated with higher 8-OHdG levels (β Q2  = 0.236, 95% CI 0.039-0.406). Compared with children having low lead exposure (quartile 1), the children with high Pb exposure (quartiles 2, 3, and 4) had significantly higher 8-OHdG levels.

Preventing, treating, and predicting barbering: A fundamental role for biomarkers of oxidative stress in a mouse model of Trichotillomania

PubMed Central

Vieira, Giovana de L. T.; Lossie, Amy C.; Lay, Donald C.; Radcliffe, John S.; Garner, Joseph P.

2017-01-01

Barbering, where a “barber” mouse plucks hair from its cagemates or itself, is both a spontaneously occurring abnormal behavior in mice and a well validated model of Trichotillomania (TTM). N-Acetylcysteine, (NAC) a cysteine derived food additive, is remarkably effective in treating TTM patients, but its mechanism of action is unknown. Reactive Oxygen Species (ROS), also known as free radicals, form as a natural byproduct of the normal metabolism of oxygen. Under normal circumstances, cells are able to defend themselves against ROS damage with antioxidant pathways. NAC is the precursor to the main antioxidant produced to defend the brain. Therefore, we hypothesized that barbering is a disease of oxidative stress, whereby ROS and/or a failure of antioxidant defenses leads to neuronal damage that induces barbering in susceptible animals. We tested this hypothesis in 32 female C57BL/6J mice by treating half with 1g/kg BW/day of NAC in their diet, and testing for protection against developing barbering behavior and curing of barbering behavior, and simultaneously testing for a panel of biomarkers of oxidative stress. NAC reduced the chance that mice would be barbers, and this effect did not differ between healthy (i.e. prevention) and affected animals (i.e. cure). Barbering animals had elevated urinary antioxidant capacity, indicative of oxidative stress, at all timepoints. Additionally, after treatment the risk of barbering increased with decreasing hydroxy-2′-deoxyguanosine (8-OHdG) levels, and with increasing glutathione (GSH) and oxidized glutathione (GSSG) levels, further indicating that barbering mice were under oxidative stress regardless of treatment with NAC. We did not find compelling evidence that urinary total antioxidant capacity, or urinary 8-OHdG, could predict response to NAC treatment. We conclude that NAC is effective in preventing and/or curing barbering at least in part by promoting GSH synthesis, thereby preventing oxidative damage. PMID:28426681

Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

PubMed Central

Mumcu, Ugur Yilmaz; Kocer, Ibrahim; Ates, Orhan; Alp, H. Hakan

2016-01-01

To investigate the malondialdehyde (MDA) levels, paraoxonase1 (PON1) activity and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels in the primary open angle glaucoma (POAG) patient. Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHdG by HPLC (high-performance liquid chromatography) and PON1 by spectrophotometry. The data obtained were analyzed statistically. MDA levels were 10.46±8.4 and 4.70±1.79 µmol; PON1 levels were 121±39.55 and 161.62±60.22 U/mL; and 8-OHdG values were 1.32±0.53/106 dG and 0.47±0.27/106 dG in the POAG patients and the control group, respectively. The difference was significant in MDA levels, 8-OHdG levels and PON1 activity in POAG patients in comparison with controls (P<0.001). We concluded that the observed increase in MDA and 8-OHdG levels may be correlated with decreased PON1 activity. Oxidative stress plays an important role in glaucoma development. PMID:27803873

Mechanism of oxidative DNA damage induction in a strict anaerobe, Prevotella melaninogenica.

PubMed

Takeuchi, T; Kato, N; Watanabe, K; Morimoto, K

2000-11-01

We investigated the mechanism of the oxidative DNA damage induction by exposure to O(2) in Prevotella melaninogenica, a strict anaerobe. Flow cytometry with hydroethidine and dichlorofluorescein diacetate showed that O(2) exposure generated O(2)*-) and H(2)O(2). Results of electron spin resonance with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone and ethanol showed that O(2) exposure also induced *OH radical generation in P. melaninogenica loaded with FeCl(2) but not in samples without FeCl(2) loading. In P. melaninogenica, O(2) exposure increased 8-hydroxydeoxyguanosine (8OHdG), typical of oxidative DNA damage. Catalase inhibited the increase, but the *OH radical scavengers did not. Phenanthroline, a membrane-permeable Fe and Cu chelator, increased the 8OHdG induction. In FeCl(2)-loaded samples, induction of 8OHdG decreased. Addition of H(2)O(2) markedly increased 8OHdG levels. These results indicate that in P. melaninogenica, exposure to O(2) generated and accumulated O(2)* and H(2)O(2), and that a crypto-OH radical generated through H(2)O(2) was the active species in the 8OHdG induction.

Placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction.

PubMed

Yoshida, Atsumi; Watanabe, Kazushi; Iwasaki, Ai; Kimura, Chiharu; Matsushita, Hiroshi; Wakatsuki, Akihiko

2018-04-01

The purpose of this study was to investigate the relationship between placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction (FGR). We examined serum concentrations of oxygen free radicals (d-ROMs), maternal angiogenic factor (PlGF), and sFlt-1, placental oxidative DNA damage, and maternal endothelial function in 17 women with early-onset preeclampsia (PE), 18 with late-onset PE, 14 with normotensive FGR, and 21 controls. Flow-mediated vasodilation (FMD) was assessed as a marker of maternal endothelial function. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Maternal serum d-ROM, sFlt-1 concentrations, and FMD did not significantly differ between the control and normotensive FGR groups. The proportion of nuclei staining positive for 8-OHdG was significantly higher in the normotensive FGR group relative to the control group. Our findings demonstrate that, despite the presence of placental oxidative DNA damage as observed in PE patients, pregnant women with normotensive FGR show no increase in the concentrations of sFlt-1 and d-ROMs, or a decrease in FMD.

Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

PubMed

Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

2015-12-01

Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Oxidative Stress Measures of Lipid and DNA Damage in Human Tears.

PubMed

Haworth, Kristina M; Chandler, Heather L

2017-05-01

We evaluate feasibility and repeatability of measures for lipid peroxidation and DNA oxidation in human tears, as well as relationships between outcome variables, and compared our findings to previously reported methods of evaluation for ocular sun exposure. A total of 50 volunteers were seen for 2 visits 14 ± 2 days apart. Tear samples were collected from the inferior tear meniscus using a glass microcapillary tube. Oxidative stress biomarkers were quantified using enzyme-linked immunosorbent assay (ELISA): lipid peroxidation by measurement of hexanoyl-lysine (HEL) expression; DNA oxidation by measurement of 8-oxo-2'-deoxyguinosone (8OHdG) expression. Descriptive statistics were generated. Repeatability estimates were made using Bland-Altman plots with mean differences and 95% limits of agreement were calculated. Linear regression was conducted to evaluate relationships between measures. Mean (±SD) values for tear HEL and 8OHdG expression were 17368.02 (±9878.42) nmol/L and 66.13 (±19.99) ng/mL, respectively. Repeatability was found to be acceptable for both HEL and 8OHdG expression. Univariate linear regression supported tear 8OHdG expression and spring season of collection to be predictors of higher tear HEL expression; tear HEL expression was confirmed as a predictor of higher tear 8OHdG expression. We demonstrate feasibility and repeatability of estimating previously unreported tear 8OHdG expression. Seasonal temperature variation and other factors may influence tear lipid peroxidation. Support is demonstrated to suggest lipid damage and DNA damage occur concurrently on the human ocular surface.

Toxicity of different forms of graphene in a chicken embryo model.

PubMed

Szmidt, Maciej; Sawosz, Ewa; Urbańska, Kaja; Jaworski, Sławomir; Kutwin, Marta; Hotowy, Anna; Wierzbicki, Mateusz; Grodzik, Marta; Lipińska, Ludwika; Chwalibog, André

2016-10-01

In the present work, the toxicity of three forms of graphene: pristine graphene (pG), graphene oxide (GO), and reduced graphene oxide (rGO) was investigated using a chicken embryo model. Fertilized chicken eggs were divided into the control group and groups administered with pG, GO, and rGO, in concentrations of 50, 500, and 5000 μg/ml. The experimental solutions were injected in ovo into the eggs, and at day 18 of incubation, the embryo survival, body and organ weights, the ultrastructure of liver samples, and the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the livers were measured. Survival of embryos decreased significantly after treatment with all types of graphene, but not in a dose-dependent manner. The body weights were only slightly affected by the highest doses of graphene, while the organ weights were not different among treatment groups. In all experimental groups, atypical hepatocyte ultrastructure and mitochondrial damage were observed. The concentration of the marker of DNA damage 8-OHdG in the liver significantly decreased after pG and rGO treatments. Further in vivo studies with different animal models are necessary to clarify the level of toxicity of different types of graphene and to estimate the concentrations appropriate to evaluate their biomedical applications and environmental hazard.

Randomized Clinical Trial of Brewed Green and Black Tea in Men with Prostate Cancer Prior to Prostatectomy

PubMed Central

Henning, Susanne M.; Wang, Piwen; Said, Jonathan W.; Huang, Min; Grogan, Tristan; Elashoff, David; Carpenter, Catherine L.; Heber, David; Aronson, William J.

2014-01-01

Background Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. Methods In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation [nuclear and cytoplasmic nuclear factor kappa B (NFκB)] and oxidation [8-hydroxydeoxy- guanosine (8OHdG)]. Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. Results Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFkB was significantly decreased in RP tissue of men consuming GT (p=0.013) but not BT (p=0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (p=0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (p=0.04). Conclusion Given the GT-induced changes in NFkB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis. PMID:25545744

Oxidative Stress Assessment in Response to Ultraendurance Exercise: Thiols Redox Status and ROS Production according to Duration of a Competitive Race

PubMed Central

Vezzoli, Alessandra; Dellanoce, Cinzia; Montorsi, Michela; Tonini, Annamaria; Accinni, Roberto

2016-01-01

Purpose. Response to an ultraendurance competitive race on thiols redox status, reactive oxygen species (ROS) production, and oxidative stress (OxS) was investigated according to duration. Methods. Twenty-four elite runners were examined: six completed 50 km and eighteen 100 km. Blood and urine samples were collected before and immediately after the race. Erythrocytes and plasma aminothiols by high-performance liquid chromatography, total antioxidant capacity (TAC), and OxS biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS), 8-isoprostane (8-iso-PGF2α), and 8-OH-2-deoxyguanosine (8-OH-dG)) by immunoenzymatic assays and ROS production by Electron Paramagnetic Resonance were assessed. Results. Significant increases (P between <0.05 and <0.0001) were recorded in plasma total and oxidized aminothiols concentration and TAC (P < 0.0001) only after 100 km: plasmatic (ROS production (+12 versus +29%), PC (+54 versus +115%), and TBARS (+28 versus +55%)) and urinary (8-OH-dG.creatinine−1 (+71 versus +158%) and 8-iso-PGF2α.creatinine−1 (+43 versus +135%)) concentrations for 50 and 100 km (duration 4 h 3′ versus 8 h 42′), respectively. Conclusion. Very prolonged ultraendurance exercise causes an increase in ROS production and OxS depending on specific biomarker examined but always linearly and directly related to exercise duration. Redox status of erythrocytes was preserved. A relationship between running performance and both prerace ROS production and antioxidant-redox status was found in 100 km race. PMID:27504148

Establishment of a reference value for chromium in the blood for biological monitoring among occupational chromium workers.

PubMed

Li, Ping; Li, Yang; Zhang, Ji; Yu, Shan-Fa; Wang, Zhi-Liang; Jia, Guang

2016-10-01

The concentration of chromium in the blood (CrB) has been confirmed as a biomarker for occupational chromium exposure, but its biological exposure indices (BEIs) are still unclear, so we collected data from the years 2006 and 2008 (Shandong Province, China) to analyze the relationship between the concentration of chromium in the air (CrA) of the workplaces and CrB to establish a reference value of CrB for biological monitoring of occupational workers. The levels of the indicators for nasal injury, kidney (β2 microglobulin (β2-MG)), and genetic damages (8-hydroxy-deoxyguanosine (8-OHdG) and micronucleus (MN)) were measured in all subjects of the year 2011 (Henan Province, China) to verify the protective effect in this reference value of CrB. Compared with the control groups, the concentrations of CrA and CrB in chromium exposed groups were significantly higher (P < 0.05). Positive correlations were found between CrA and CrB in chromium exposed groups (r 2006 = 0.60, r 2008 = 0.35) in the years 2006 and 2008. According to the occupational exposure limitation of CrA (50 μg/m(3), China), the reference value of CrB was recommended to 20 μg/L. The levels of nasal injury, β2-MG, 8-OhdG, and MN were not significantly different between the low chromium exposed group (CrB ≤ 20 μg/L) and the control group, while the levels of β2-MG, 8-OHdG, and MN were statistically different in the high chromium exposed group than that in the control group. This research proved that only in occupational workers, CrB could be used as a biomarker to show chromium exposure in the environment. The recommended reference value of CrB was 20 μg/L. © The Author(s) 2015.

Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein.

PubMed

Wei, Huachen; Zhang, Xueshu; Wang, Yan; Lebwohl, Mark

2002-11-08

We have previously demonstrated that soybean isoflavone genistein inhibits ultraviolet-B (UVB)-induced skin tumorigenesis in hairless mice. In the present study, we further investigated the possible mechanism(s) of action whereby genistein inhibits photocarcinogenesis with focuses on UVB-induced oxidative events, including hydrogen peroxide (H(2)O(2)) production, lipid peroxidation (as represented by malondialdehyde, MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in vivo. We demonstrated that subacute exposure to UVB substantially increased the level of H(2)O(2), lipid peroxides, and 8-OHdG in skin of hairless mice. In addition, chronic exposure to low-dose UVB (0.9-1.2 kJ/m(2) for 20 weeks) substantially increased the levels of 8-OHdG not only in the epidermis, but also in the internal organs such as liver, brain, and spleen of mice with exception of kidney. However, genistein did not affect the level of UVB-induced pyrimidine dimmers in the same UVB exposed mouse skin, indicating selective inhibition of oxidative DNA damage by genistein. Induction of H(2)O(2) was independent of UVB fluences whereas the levels of MDA and 8-OHdG were induced in an UVB fluence-dependent manner. The results suggest that H(2)O(2) be generated as an acute cutaneous response to UVB irradiation, while MDA and 8-OHdG are accumulated with increasing UVB exposure and more closely related to chronic effects of UVB radiation. Pre-treatment of animals with 10 micromol of genistein 1 h prior to UVB exposure significantly inhibited UVB-induced H(2)O(2) and MDA in skin and 8-OHdG in epidermis as well as internal organs. Suppression of 8-OHdG formation by genistein has been corroborated in purified DNA irradiated with UVA and B. In summary, our results suggest that UVB irradiation elicit a series of oxidative events, which can be substantially inhibited by isoflavonoid genistein through either direct quenching of reactive oxygen species or indirect antiinflammatory effects. Thus, the antioxidative properties of genistein may explain for the mechanisms of anti-photocarcinogenic action of genistein.

Part 3. Assessment of genotoxicity and oxidative damage in rats after chronic exposure to new-technology diesel exhaust in the ACES bioassay.

PubMed

Hallberg, Lance M; Ward, Jonathan B; Hernandez, Caterina; Ameredes, Bill T; Wickliffe, Jeffrey K

2015-01-01

In 2001, the U.S. Environmental Protection Agency (EPA*) and the California Air Resources Board (CARB) adopted new standards for diesel fuel and emissions from heavy-duty diesel engines. By 2007, diesel engines were required to meet these new standards for particulate matter (PM), with other standards to follow. Through a combination of advanced compression-ignition engine technology, development of exhaust aftertreatment systems, and reformulated fuels, stringent standards were introduced. Before the 2007 standards were put in place by the EPA, human health effects linked to diesel exhaust (DE) exposure had been associated with diesel-fuel solvent and combustion components. In earlier research, diesel engine exhaust components were, in turn, linked to increased mutagenicity in cultures of Salmonella typhimurium and mammalian cells (Tokiwa and Ohnishi 1986). In addition, DE was shown to increase both the incidence of tumors and the induction of 8-hydroxy-deoxyguanosine (8-OHdG) adducts in rodents (Ichinose et al. 1997) and total DNA adducts in rats (Bond et al. 1990). Furthermore, DE is composed of a complex mixture of polycyclic aromatic hydrocarbons (PAHs) and particulates. One such PAH, 3-nitrobenzanthrone (3-NBA), is also found in urban air. 3-NBA has been observed to induce micronucleus formation in the DNA of human hepatoma cells (Lamy et al. 2004). The current study is part of the Advanced Collaborative Emissions Study (ACES), a multidisciplinary program carried out by the Health Effects Institute and the Coordinating Research Council. Its purpose was to determine whether recent improvements in the engineering of heavy-duty diesel engines reduce the toxicity associated with exposure to DE components. To this end, we evaluated potential genotoxicity and induction of oxidative stress in bioassays of serum and tissues from Wistar Han rats chronically exposed--for up to 24 months--to DE from a 2007-compliant diesel engine (new-technology diesel exhaust, or NTDE). Genotoxicity was measured as DNA strand breaks in lung tissue, using an alkaline-modified comet assay. As a correlate of possible DNA damage evaluated in the comet assay, concentrations of the free DNA adduct 8-OHdG were evaluated in serum by a competitive enzyme-linked immunosorbent assay (ELISA). The 8-OHdG fragment found in the serum is a specific biomarker for the repair of oxidative DNA damage. In addition, an assay for thiobarbituric acid reactive substances (TBARS) was used to assess oxidative stress and damage in the form of lipid peroxidation in the hippocampus region of the brains of the DE-exposed animals. These endpoints were evaluated at 1, 3, 12, and 24 months of exposure to DE or to a control atmosphere (filtered air). At the concentrations of DE evaluated, there were no significant effects of exposure in male or female rats after 1, 3, 12, or 24 months in any measure of DNA damage in the comet assay (%DNA in tail, tail length, tail moment, or olive moment). The comparison of exposure groups versus control and the comparison of groups by sex for 1 and 3 months of exposure showed no significant differences in serum 8-OHdG concentrations (P > 0.05). The concentrations of 8-OHdG in all exposure groups at 3 months were higher than those in exposure groups at any other time point (P < 0.05). Looking at the levels of 8-OHdG in serum in the 12-month and 24-month groups, we saw a significant difference from control in the 12-month group at the mid and high levels (P < 0.05), as well as some other scattered changes. Sex differences were noted in the 12-month high-level group (P < 0.05). However, these differences did not follow an exposure-dependent pattern. All other comparisons were not significant (P > 0.05). Hippocampal concentrations of TBARs, measured as malondialdehyde (MDA), showed some small and scattered changes in groups exposed to different levels of DE and at different time points, but we did not consider these to be exposure-related. We concluded that exposure to DE in these rats did not produce any significant increase in oxidative damage to lipids or damage to DNA in the form of strand breaks.

Study of DNA adduct 8 hydroxy-2’-deoxyguanosine (8-OHdG) formation through fenton reaction with tert-butylhydroquinone (TBHQ) and butyl hydroxy toluene (BHT)

NASA Astrophysics Data System (ADS)

Handayani, S.; Dani, I. C.; Budiawan; Pakuanisa, D.

2017-05-01

The research of DNA adduct formation 8-hydroxy-2’-Deoxyguanosine (8-OHdG) as a biomarker of DNA damage due to oxidative stress was carried out by reacting the DNA base 2’-deoxyguanosine-5’-monophosphate with TBHQ and BHT. The formationof 8-OHdG was carried out in various conditions, at temperature of 37° C and 60° C, pH 7.4 and pH 8.4, within 5 hours of incubation time and in the addition of FeSO4. The formation of DNA adducts profile were analyzed using reversed phase HPLC with UV detector at a wavelength of 254 nm. The results of the study showed that TBHQ and BHT can trigger the formation of 8-OHdG from the reaction of 2’-hydroxy Deoxyguanosine-5’-monophosphate in the presence of Fe (II). Meanwhile, in the addition of hydrogen peroxide, the formation of DNA adducts only occur in the test substance TBHQ. The results showed that the condition of higher temperature at 60°C and pH 8,4 affects the higher formation of DNA adducts.

The influence of the occupational exposure to heavy metals and tobacco smoke on the selected oxidative stress markers in smelters.

PubMed

Sciskalska, Milena; Zalewska, Marta; Grzelak, Agnieszka; Milnerowicz, Halina

2014-06-01

The aim of the study was to verify if there is any association between exposure to Cu, Zn, Cd, Pb, As and the formation of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), and whether in this process cigarette smoking plays a role. The investigations were performed in the 352 smelters occupationally exposed to heavy metals and 73 persons of control group. Metals concentration was determined by atomic absorption spectrometry. MDA and AOPP concentrations were determined by spectrophotometric methods. The concentration of 8-OHdG was determined by ELISA method. It was demonstrated an increased Cu concentration in smoking smelters compared to non-smoking control group. It was noted no differences in Zn and Mg concentrations between the examined groups. Pb concentration was more than sixfold higher in the group of smoking smelters and about fivefold higher in the group of non-smoking smelters compared to the control groups (smokers and non-smokers). It was shown that Cd concentration in the blood was nearly fivefold higher in the smoking control group compared to the non-smoking control group and more than threefold higher in the group of smoking smelters compared to non-smoking. It was shown an increased As concentration (more than fourfold) and decreased Ca concentration in both groups of smelters compared to control groups. In groups of smelters (smokers and non-smokers), twofold higher MDA and AOPP concentrations, and AOPP/albumin index compared to control groups (smokers and non-smokers) were shown. Tobacco smoke is the major source of Cd in the blood of smelters. Occupational exposure causes accumulation of Pb in the blood. Occupational exposure to heavy metals causes raise of MDA concentration and causes greater increase in AOPP concentration than tobacco smoke.

Application of Hyperbaric Oxygen Reduce Oxidative Damage of Plasmatic Carbonyl Proteins and 8-OHdG by Activating Glutathion Peroxidase.

PubMed

Matzi, Veronika; Greilberger, Joachim F; Lindenmann, Joerg; Neuboeck, Nicole; Nuhsbaumer, Stephan; Zelzer, Sieglinde; Tafeit, Erwin; Maier, Alfred; Smolle-Juettner, Maria-Frey

2015-01-01

It is postulated that application of hyperbaric oxygenation may induce the production of radicals after HBO. Higher oxygenation and transport of oxygen increase the mitochondrial energy turnover, whereas inner mitochondrial radical formation decreases. Several markers of oxidative stress in healthy volunteers (n = 21), including plasma carbonyl proteins (CP), malondialdehyde (MDA), oxidized LDL (oxLDL), 8-hydroxy-deoxyguanosine (8-OHdG), and erythrocyte glutathione peroxidase (GPx) activity are measured before, during, and after HBO. Median plasma concentrations of CP decreased significantly during HBO compared to CP levels before HBO (from 77.1 to 61.7 pmol/mg; p < 0.001) and increased again after HBO (to 78.1 pmol/mg; p = 0.035). 8-OHdG decreased significantly during HBO (8.1 ng/mL; p < 0.001) and remained constant after HBO (8.1 ng/mL) compared to "before HBO" (9.4 ng/mL). MDA increased significantly from 0.92 μM (before HBO) to 1.26 μM (during HBO, p < 0.01) and decreased again to 1.00 μM (after HBO, p = 0.023). Erythrocyte GPx activity also increased significantly during HBO (26.5 ± 14.7; p = 0.005), but not after HBO (25.6 ± 17.2 IU/mg). A negative correlation was observed between GPx and MDA only during HBO (r = -0.518; p = 0.016). We assume that higher oxygen consumption decreases, on the one hand, the inner mitochondrial generation of free radicals and, on the other, RONS by activation of detoxifying enzymes like GPx.

Biomarkers of oxidative stress and DNA damage in agricultural workers: A pilot study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muniz, Juan F.; McCauley, Linda; Scherer, J.

Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. A study of pesticide applicators and farmworkers was conducted to examine the relationship between organophosphate pesticide exposure and biomarkers of oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for oxidative DNA repair activity and DNA damage (Comet assay), and serum was analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in agricultural workers was validated using lymphocyte cell cultures. Urinary OP metabolites were significantly higher in farmworkers andmore » applicators (p < 0.001) when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in farmworkers or applicators (respectively) than in controls. Serum MDA levels were 4.9 times and 24 times higher in farmworkers or applicators (respectively) than in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly greater in lymphocytes from applicators and farmworkers when compared with controls. Markers of oxidative stress (i.e., increased reactive oxygen species and reduced glutathione levels) and DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. These biomarkers may be useful for increasing our understanding of the link between pesticides and a number of health effects.« less

Time-Course Changes of Oxidative Stress Response to High-Intensity Discontinuous Training versus Moderate-Intensity Continuous Training in Masters Runners

PubMed Central

Vezzoli, Alessandra; Pugliese, Lorenzo; Marzorati, Mauro; Serpiello, Fabio Rubens; La Torre, Antonio; Porcelli, Simone

2014-01-01

Beneficial systemic effects of regular physical exercise have been demonstrated to reduce risks of a number of age-related disorders. Antioxidant capacity adaptations are amongst these fundamental changes in response to exercise training. However, it has been claimed that acute physical exercise performed at high intensity (>60% of maximal oxygen uptake) may result in oxidative stress, due to reactive oxygen species being generated excessively by enhanced oxygen consumption. The aim of this study was to evaluate the effect of high-intensity discontinuous training (HIDT), characterized by repeated variations of intensity and changes of redox potential, on oxidative damage. Twenty long-distance masters runners (age 47.8±7.8 yr) on the basis of the individual values of gas exchange threshold were assigned to a different 8-weeks training program: continuous moderate-intensity training (MOD, n = 10) or HIDT (n = 10). In both groups before (PRE) and after (POST) training we examined the following oxidative damage markers: thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxidation; protein carbonyls (PC) as marker of protein oxidation; 8-hydroxy-2-deoxy-guanosine (8-OH-dG) as a biomarker of DNA base modifications; and total antioxidant capacity (TAC) as indicator of the overall antioxidant system. Training induced a significant (p<0.05) decrease in resting plasma TBARS concentration in both MOD (7.53±0.30 and 6.46±0.27 µM, PRE and POST respectively) and HIDT (7.21±0.32 and 5.85±0.46 µM, PRE and POST respectively). Resting urinary 8-OH-dG levels were significantly decreased in both MOD (5.50±0.66 and 4.16±0.40 ng mg−1creatinine, PRE and POST respectively) and HIDT (4.52±0.50 and 3.18±0.34 ng mg−1creatinine, PRE and POST respectively). Training both in MOD and HIDT did not significantly modify plasma levels of PC. Resting plasma TAC was reduced in MOD while no significant changes were observed in HIDT. In conclusion, these results suggest that in masters runners high-intensity discontinuous does not cause higher level of exercise-induced oxidative stress than continuous moderate-intensity training, inducing similar beneficial effects on redox homeostasis. PMID:24498121

Oxidative DNA damage and its repair in rat spleen following subchronic exposure to aniline

PubMed Central

Ma, Huaxian; Wang, Jianling; Abdel-Rahman, Sherif Z.; Boor, Paul J.; Khan, M. Firoze

2008-01-01

The mechanisms by which aniline exposure elicits splenotoxic response, especially the tumorigenic response, are not well-understood. Splenotoxicity of aniline is associated with iron overload and generation of reactive oxygen species (ROS) which can cause oxidative damage to DNA, proteins and lipids (oxidative stress). 8-Hydroxy-2’-deoxyguanosine (8-OHdG) is one of the most abundant oxidative DNA lesions resulting from ROS, and 8-oxoguanine glycosylase 1 (OGG1), a specific DNA glycosylase/lyase enzyme, plays a key role in the removal of 8-OHdG adducts. This study focused on examining DNA damage (8-OHdG) and repair (OGG1) in the spleen in an experimental condition preceding a tumorigenic response. To achieve that, male Sprague-Dawley rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. Aniline treatment led to a significant increase in splenic oxidative DNA damage, manifested as a 2.8-fold increase in 8-OHdG levels. DNA repair activity, measured as OGG1 base excision repair (BER) activity, increased by ~1.3 fold in the nuclear protein extracts (NE) and ~1.2 fold in the mitochondrial protein extracts (ME) of spleens from aniline-treated rats as compared to the controls. Real-time PCR analysis for OGG1 mRNA expression in the spleen revealed a 2-fold increase in expression in aniline-treated rats than the controls. Likewise, OGG1 protein expression in the NEs of spleens from aniline-treated rats was ~1.5 fold higher, whereas in the MEs it was ~1.3 fold higher than the controls. Aniline treatment also led to stronger immunostaining for both 8-OHdG and OGG1 in the spleens, confined to the red pulp areas. It is thus evident from our studies that aniline-induced oxidative stress is associated with increased oxidative DNA damage. The BER pathway was also activated, but not enough to prevent the accumulation of oxidative DNA damage (8-OHdG). Accumulation of mutagenic oxidative DNA lesions in the spleen following exposure to aniline could play a critical role in the tumorigenic process. PMID:18793663

Genotoxic Effects Due to Exposure to Chromium and Nickel Among Electroplating Workers.

PubMed

El Safty, Amal Mohamed Kamal; Samir, Aisha Mohamed; Mekkawy, Mona Kamal; Fouad, Marwa Mohamed

Using chromium and nickel for electroplating is important in many industries. This process induces variable adverse health effects among exposed workers. The aim of this study is to detect the genotoxic effects of combined exposure to chromium and nickel among electroplating workers. This study was conducted on 41 male workers occupationally exposed to chromium and nickel in the electroplating section of a factory compared to 41 male nonexposed individuals, where full history and clinical examination were performed. Laboratory investigations included measurement of serum chromium, nickel, 8-hydroxydeoxyguanosine (8-OHdG), and micronuclei were measured in buccal cells. In exposed workers, serum chromium ranged from 0.09 to 7.20 µg/L, serum nickel ranged from 1.20 to 28.00 µg/L, serum 8-OHdG ranged from 1.09 to12.60 ng/mL, and these results were statistically significantly increased compared to nonexposed group ( P < 0.001). Electroplaters showed higher frequencies of micronuclei in buccal cells when compared to nonexposed (ranged from 20.00 to 130.00 N/1,000 versus 2.00 to 28.00 N/1,000; P < 0.001). Linear regression models were done to detect independent predictors of 8-OHdG and micronucleus test by comparing exposed and nonexposed groups. The model found that exposure to chromium and nickel increases serum 8-OHdG by 4.754 (95% confidence interval [CI]: 3.54-5.96). The model found that exposure to chromium and nickel increases micronucleus by 35.927 (95% CI: 28.517-43.337). Serum 8-OHdG and micronucleus test in buccal cells were increased with combined exposure to chromium and nickel. The current research concluded that workers exposed to nickel and chromium in electroplating industry are at risk of significant cytogenetic damage.

Smoking status and occupational exposure affects oxidative DNA injury in boilermakers exposed to metal fume and residual oil fly ash.

PubMed

Mukherjee, Sutapa; Palmer, Lyle J; Kim, Jee Young; Aeschliman, David B; Houk, Robert S; Woodin, Mark A; Christiani, David C

2004-03-01

Epidemiologic studies demonstrate increased cancer incidence among workers exposed to polycyclic aromatic hydrocarbons (PAH) and metals, probably through cumulative oxidative DNA damage in response to carcinogens. Boilermakers are exposed to particulates of residual oil fly ash (ROFA) and metal fume that contain carcinogenic PAH and metals. We conducted a repeated-measures cohort study in boilermakers during the overhaul of an oil-fired boiler to determine a possible association between the level of 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an oxidative injury biomarker) and biomarkers of PAH (1-hydroxypyrene; 1-OHP) and metal exposure. Preshift and postshift urine samples were analyzed for 8-OH-dG, cotinine, 1-OHP, and metals. Generalized estimating equations were used to model the multivariate relationship of 8-OH-dG to the explanatory variables of interest. Biomarker levels were determined for 181 urine samples from 20 male subjects (mean age 45 years, 50% smokers). Metal and 1-OHP levels increased cross-week and were affected by smoking status. Levels of 8-OH-dG were higher in nonsmokers at the start of the workweek yet declined after occupational exposure to similar levels as in smokers. Multivariate analysis indicated that metal x cotinine interaction terms for nickel, vanadium, chromium, and copper were significantly associated with the 8-OH-dG level, but there were differential effects depending on the metal. This study suggests that oxidative DNA damage in boilermakers is influenced by the interaction between occupational exposures and smoking status. In addition, boilermakers may have reduced ability to repair damaged DNA after ROFA and metal fume exposure. This finding has clinical relevance because these exposures may increase the cancer susceptibility of boilermakers.

Health and carcinogenic risk evaluation for cohorts exposed to PAHs in petrochemical workplaces in Rawalpindi city (Pakistan).

PubMed

Kamal, Atif; Cincinelli, Alessandra; Martellini, Tania; Palchetti, Ilaria; Bettazzi, Francesca; Malik, Riffat Naseem

2016-01-01

This study presents the analyses of urinary biomarkers (1-OHPyr, α- and β-naphthols) of polycyclic aromatic hydrocarbons (PAHs) exposure and biomarkers of effect (i.e. blood parameters) in petroleum-refinery workers (RFs) and auto-repair workers (MCs). Exposed subjects had higher concentrations of white blood cell (WBC) count than control subjects (CN) subjects (5.31 × 10(3) μL(-1) in exposed vs. 5.15 × 10(3) μL(-1) in CN subjects), while the biomarker of oxidative DNA damage (8-OHdG) was significantly higher in MCs. The exposure among these two cohorts could be influenced by the ambience of the workplaces; in fact, MCs' shops are relatively damp and enclosed workplaces in comparison with the indoor environment of refineries. PAHs in the dust samples from mechanical workshops probably originated from mixed sources (traffic exhaust and petroleum spills), while the incremental lifetime cancer risk (ILCR) for MCs showed moderate-to-low cancer risk from exposure to dust-bound PAHs. The study shows that increasing PAH exposure can be traced in MC workstations and needs to be investigated for the safety of public health.

Protective role of melatonin in progesterone production by human luteal cells.

PubMed

Taketani, Toshiaki; Tamura, Hiroshi; Takasaki, Akihisa; Lee, Lifa; Kizuka, Fumie; Tamura, Isao; Taniguchi, Ken; Maekawa, Ryo; Asada, Hiromi; Shimamura, Katsunori; Reiter, Russel J; Sugino, Norihiro

2011-09-01

This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P < 0.05) and negatively correlated with the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker (r = -0.342, P < 0.05). The progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P < 0.05). Luteinized granulosa cells were obtained at the time of oocyte retrieval in women undergoing IVF-ET. Cells were incubated with H(2)O(2) (30, 50, 100 μm) in the presence or absence of melatonin (1, 10, 100 μg/mL). Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations <10 ng/mL during the mid-luteal phase) were divided into two groups during the next treatment cycle: 14 women were given melatonin (3 mg/day at 22:00 hr) throughout the luteal phase and 11 women were given no medication as a control. Melatonin treatment improved serum progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation. © 2011 John Wiley & Sons A/S.

[DNA damage in human pleural mesothelial cells induced by exposure to carbon nanotubes].

PubMed

Ogasawara, Yuki; Umezu, Noriaki; Ishii, Kazuyuki

2012-01-01

Nanomaterials are currently used in electronics, industrial materials, cosmetics, and medicine because they have useful physicochemical properties, such as strength, conductivity, durability, and chemical stability. As these materials have become widespread, many questions have arisen regarding their effects on health and the environment. In particular, recent studies have demonstrated that carbon nanotubes (CNTs) cause significant inflammation and mesothelioma in vivo. In this study, we investigated the potential risk posed by singlewalled carbon nanotube (SWCNT) and multiwalled carbon nanotube (MWCNT) exposure in human pleural mesothelial cells. CNT cytotoxicity was determined by a trypan blue exclusion assay, and DNA damage was detected by an alkaline comet assay. The concentration of 8-oxodeoxyguanosine (8-OHdG) in DNA was measured by high perhormance liquid chromatography with electrochemical detection. The expression of base excision repair enzymes in the cell was estimated by immunoblot analysis. We observed inhibitory effects on cell proliferation and the induction of DNA damage following exposure of cells to purified CNTs that were suspended in dispersion medium. However, accumulation of 8-OHdG in DNA was not found. In addition, the expression levels of base excision enzymes that are involved in hOGG1, hMTH1, and MYH in MeT-5A cells remained unchanged for 24 h after carbon nanotube exposure. CNTs significantly inhibit cell proliferation and decrease DNA damage in human pleural mesothelial cells. Our results indicate that the mechanism of CNT-induced genotoxicity is different from that following exposure to reactive oxygen species, which causes oxidative DNA modifications and 8-OHdG production. Further investigation is required to characterize the specific DNA mutations that occur following CNT exposure.

Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort.

PubMed

Black, C N; Bot, M; Scheffer, P G; Penninx, B W J H

2017-04-01

Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort. Data was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables. F2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4-43.8) compared to controls (45.0 pmol/l, 95% CI 42.9-47.2; p < 0.001) after adjustment for sampling, sociodemographics and lifestyle, but these differences disappeared after further adjustment for antidepressant use (p = 0.562). Antidepressant users had lower 8-OHdG levels (38.2 pmol/l, 95% CI 36.5-39.9) compared to controls (44.9 pmol/l, 95% CI 43.2-46.6; Cohen's d = 0.21, p < 0.001). Results for 8-OHdG were comparable across disorders (MDD and/or anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants). Contrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects.

Environmental conditions can modulate the links among oxidative stress, age, and longevity.

PubMed

Marasco, Valeria; Stier, Antoine; Boner, Winnie; Griffiths, Kate; Heidinger, Britt; Monaghan, Pat

2017-06-01

Understanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early- and mid-adulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2'-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age-related change. Copyright © 2017 Elsevier B.V. All rights reserved.

Elevated Levels of Urinary 8-Hydroxy-2′-deoxyguanosine, Lymphocytic Micronuclei, and Serum Glutathione S-Transferase in Workers Exposed to Coke Oven Emissions

PubMed Central

Liu, Ai-Lin; Lu, Wen-Qing; Wang, Zeng-Zhen; Chen, Wei-Hong; Lu, Wen-Hong; Yuan, Jing; Nan, Pei-Hong; Sun, Jian-Ya; Zou, Ya-Lin; Zhou, Li-Hong; Zhang, Chi; Wu, Tang-Chun

2006-01-01

To investigate associations among occupational exposure to coke oven emissions (COEs), oxidative stress, cytogenotoxic effects, change in the metabolizing enzyme glutathione S-transferase (GST), and internal levels of polycyclic aromatic hydrocarbons (PAHs) in coke oven workers, we recruited 47 male coke oven workers and 31 male control subjects from a coke oven plant in northern China. We measured the levels of 1-hydroxypyrene (1-OHP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urine, micronucleated binucleated cells (BNMNs) in peripheral blood lymphocyte, and GST in serum. Our results showed that the group exposed to COEs had significantly increased levels of 1-OHP [median 5.7; interquartile range (IQR), 1.4–12.0 μmol/mol creatinine] compared with the control group (3; 0.5–6.4 μmol/mol creatinine). In addition, the median levels (IQR) of 8-OHdG, BNMNs, and GST were markedly increased in the exposed [1.9 (1.4–15.4) μmol/mol creatinine; 6 (2–8) per thousand; 22.1 (14.9–31.2) U/L, respectively] compared with controls [1.3 (1.0–4.0) μmol/mol creatinine, 2 (0–4) per thousand; and 13.1 (9.5–16.7) U/L, respectively]. These results appeared to be modified by smoking. However, multivariate logistic regression analysis revealed that exposure to COEs had the highest odds ratio among variables analyzed and that smoking was not a significant confounder of the levels of studied biomarkers. Overall, the present findings suggest that COE exposure led to increased internal PAH burden, genetic damage, oxidative stress, and GST activity. The consequences of the changes in these biomarkers, such as risk of cancer, warrant further investigations. PMID:16675419

Pycnogenol (PYC) induces apoptosis in human fibrosarcoma (HFS) cells under metal-mediated oxidative stress.

PubMed

Park, Yeon Sun; Kim, Young Gon

2011-01-01

Pycnogenol (PYC), polyphenolic compounds with antioxidant activity, acted as a prooxidant. PYC caused oxidative stress in human fibrosarcoma cells (HFS) when administered following pretreatment with iron chloride. The generated reactive oxygen species (ROS) caused the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA and resulted in more apoptosis in HFS cells than in the human fibroblastoma (HFB) cells. DNA damage and cellular viability at different PYC concentrations were closely consistent with cell growth, high performance liquid chromatography (HPLC), Enzyme Linked Immunosorbent Assay (ELISA) and assays of two major antioxidant enzymes, superoxide dismutase (SOD) and catalase. Although the presence of PYC induced total SOD and catalase activities under oxidative stress in dose dependent fashion, more apoptotic cells were induced in HFS cells with increased [8-OHdG] than in HFB cells. The results suggest that PYC selectively induced cell death in HFS cells. This further confirmed that PYC-induced apoptosis is mediated primarily through the activation of caspase-3 apoptotic marker in HFS cells but not in HFB cells. We conclude that PYC would behave as either antioxidant or prooxidant dependant upon the cellular types.

Effect of uric acid on mitochondrial function and oxidative stress in hepatocytes.

PubMed

Yang, Y; Zhou, Y; Cheng, S; Sun, J L; Yao, H; Ma, L

2016-06-24

Here, we investigated the effect of uric acid (UA) on hepatocyte mitochondria. Hepatocytes cultured in vitro were treated with varying concentrations of UA. The change in apoptotic activity was detected by flow cytometry. The DNA damage index 8-hydroxy-deoxy-guanosine (8-OHdG) and mitochondrial function indices succinate dehydrogenase (SDH), cytochrome C oxidase (CCO), and adenosine triphosphate (ATP) were detected by enzyme assays. Reactive oxygen species (ROS) accumulation was confirmed by a dichloro-dihydro-fluorescein diacetate assay. We observed an increase in apoptotic activity, ROS accumulation, and 8-OHdG activity in hepatocytes treated with UA for extended periods, indicating DNA damage; specifically, we observed a significant increase in these activities 48, 72, and 96 h after UA addition, compared to those observed at 24 h (P < 0.05). Cells treated with 30 mg/dL UA for 96 h showed a peak in apoptotic activity. We also observed a significant decrease in ATP, SDH, and CCO activities with the increase in uric acid concentration over time. Cells treated with 30 mg/dL UA for 96 h showed the highest ATP levels, while SDH and CCO activities at 48, 72, and 96 h post-UA treatment were significantly lower than those at 24 h (P < 0.01). Moreover, cells treated with 30 mg/dL UA showed a 0.02 ± 0.02 and 0.15 ± 0.01 mmol/ mg/min decrease in SDH and CCO levels after 72 h. Therefore, we concluded that high concentrations of UA may induce oxidative stress in hepatocyte mitochondria, increasing ROS production and ultimately resulting in mitochondrial damage.

Melatonin Ameliorates The Production of COX-2, iNOS, and The Formation of 8-OHdG in Non-Targeted Lung Tissue after Pelvic Irradiation.

PubMed

Fardid, Reza; Salajegheh, Ashkan; Mosleh-Shirazi, Mohammad Amin; Sharifzadeh, Sedigheh; Okhovat, Mohammad Ali; Najafi, Masoud; Rezaeyan, Abolhasan; Abaszadeh, Akbar

2017-01-01

In this study, we evaluated the bystander effect of radiation on the regulation of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and 8-hydroxydeoxyguanosine (8-OHdG) in lung tissues of Sprague-Dawley rats with and without pre-administration of melatonin. A 2×2 cm 2 area of the pelvis of male Sprague-Dawley rats with and without pre-administration of melatonin (100 mg/kg) by oral and intraperitoneal injection was irradiated with a 3 Gy dose of 1.25 MeV γ-rays. Alterations in the levels of COX-2, iNOS, and 8-OHdG in the out-of-field lung areas of the animals were detected by enzyme immunoassay. The bystander effect significantly increased COX-2, iNOS, and 8-OHdG levels in non-targeted lung tissues (P<0.05). Melatonin ameliorated the bystander effect of radiation and significantly reduced the level of all examined biomarkers (P<0.05). The results indicated that the ameliorating effect of a pre-intraperitoneal (IP) injection of melatonin was noticeably greater compared to oral pre-administration. Our findings revealed that the bystander effect of radiation could induce oxidative DNA damage and increase the levels of imperative COX-2 and iNOS in non-targeted lung tissues. Interestingly, melatonin could modulate the indirect destructive effect of radiation and reduce DNA damage in non-targeted cells.

Comparative embryotoxicity of a pentabrominated diphenyl ether mixture to common terns (Sterna hirundo) and American kestrels (Falco sparverius)

USGS Publications Warehouse

Rattner, Barnett A.; Lazarus, Rebecca S.; Heinz, Gary H.; Karouna-Reiner, Natalie K.; Schultz, Sandra L.; Hale, Robert C.

2013-01-01

Concentrations of polybrominated diphenyl ethers (PBDEs) in Forster’s tern (Sterna forsteri) eggs from San Francisco Bay have been reported to range up to 63 μg g−1 lipid weight. This value exceeds the lowest-observed-adverse-effect level (1.8 μg g−1 egg wet weight; ∼32 μg−1 lipid weight) reported in an embryotoxicity study with American kestrels (Falco sparverius). As a surrogate for Forster’s terns, common tern (Sterna hirundo) eggs were treated by air cell injection with corn oil vehicle (control) or a commercial penta-BDE formulation (DE-71) at nominal concentrations of 0.2, 2, and 20 μg g−1 egg. As a positive control, kestrel eggs received vehicle or 20 μg DE-71 g−1 egg. In terns, there were no effects of DE-71 on embryonic survival, and pipping or hatching success; however, treated eggs hatched later (0.44 d) than controls. Organ weights, organ-to-body weight ratios, and bone lengths did not differ, and histopathological observations were unremarkable. Several measures of hepatic oxidative stress in hatchling terns were not affected by DE-71, although there was some evidence of oxidative DNA damage (8-hydroxy-deoxyguanosine; 8-OH-dG). Although DE-71 did not impair pipping and hatching of kestrels, it did result in a delay in hatch, shorter humerus length, and reduced total thyroid weight. Concentrations of oxidized glutathione, reduced glutathione, thiobarbituric acid reactive substances, and 8-OH-dG in liver were greater in DE-71-treated kestrels compared to controls. Our findings suggest common tern embryos, and perhaps other tern species, are less sensitive to PBDEs than kestrel embryos.

Cigarette smoking and hOGG1 Ser326Cys polymorphism are associated with 8-OHdG accumulation on mitochondrial DNA in thoracic esophageal squamous cell carcinoma.

PubMed

Lin, Chen-Sung; Wang, Liang-Shun; Chou, Teh-Ying; Hsu, Wen-Hu; Lin, Hui-Chen; Lee, Shu-Yu; Lee, Mau-Hua; Chang, Shi-Chuan; Wei, Yau-Huei

2013-12-01

We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC). DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing. Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051). Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.

Panax ginseng Fraction F3 Extracted by Supercritical Carbon Dioxide Protects against Oxidative Stress in ARPE-19 Cells.

PubMed

Yang, Chao-Chin; Chen, Chiu-Yuan; Wu, Chun-Chi; Koo, Malcolm; Yu, Zer-Ran; Wang, Be-Jen

2016-10-13

In our previous work, the ethanolic extract of Panax ginseng C. A. Meyer was successively partitioned using supercritical carbon dioxide at pressures in series to yield residue (R), F1, F2, and F3 fractions. Among them, F3 contained the highest deglycosylated ginsenosides and exerted the strongest antioxidant and anti-inflammatory activities. The aim of this study was to investigate the protective effects of P. ginseng fractions against cellular oxidative stress induced by hydrogen peroxide (H₂O₂). Viability of adult retinal pigment epithelium-19 (ARPE-19) cells was examined after treatments of different concentrations of fractions followed by exposure to H₂O₂. Oxidative levels (malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reactive oxygen species (ROS)) and levels of activity of antioxidant enzymes were assessed. Results showed that F3 could dose-dependently protected ARPE-19 cells against oxidative injury induced by H₂O₂. F3 at a level of 1 mg/mL could restore the cell death induced by H₂O₂ of up to 60% and could alleviate the increase in cellular oxidation (MDA, 8-OHdG, and ROS) induced by H₂O₂. Moreover, F3 could restore the activities of antioxidant enzymes suppressed by H₂O₂. In conclusion, F3 obtained using supercritical carbon dioxide fractionation could significantly increase the antioxidant capacity of P. ginseng extract. The antioxidant capacity was highly correlated with the concentration of F3.

The effect of oral and intraurethral trimetazidine use on urethral healing

PubMed Central

Ayyildiz, Ali; Ayyildiz, Sema Nur; Benli, Erdal; Erdem, Havva; Cirrik, Selma; Noyan, Tevfik; Germiyanoglu, R. Cankon; Çirakoglu, Abdullah

2016-01-01

Objective(s): We aimed to study the effect of trimetazidine (TMZ) on urethral wound repair. Materials and Methods: A total of 52 male rats were used; 8 groups were formed: 1-week and 3-week control (C1, C3), sham (S1, S3), oral (OT1, OT3), and intraurethral TMZ (IUT1, IUT3) groups. Serum and urine total antioxidant capacity (TAC), total oxidant capacity (TOC), and 8-hydroxy-deoxy-guanosine (8-OHdG) were studied. Hematoxyline-Eosin was used for the histopathological study. In addition, tumor necrosis factor alpha (TNF- α), interleukin 1α, and β levels were compared across groups by an immunohistochemical method. Results: There were significant differences between C3 and IUT3, OT3 and IUT3 with respect to serum TAC in 3-week groups (P=0.013; P =0.001). Serum TOC levels were significantly different between C3 and IUT3; S3 and OT3; and OT3 and IUT3 groups (P =0.024; P =0.019; P =0.000, respectively). Serum 8-OHdG levels were significantly different between C3 and OT3 groups (P=0.033). In the immunohistochemical examination, C1 and OT1; C1 and IUT1; and S1, S3, OT1, OT3, IUT1 groups were significantly different with respect to IL-1β staining (P=0.007; P =0.000; P=0.009), while there was a significant difference between C3 and S3 with respect to IL-1β (P =0.000). Conclusion: TMZ increased urinary total oxidant level; while increasing serum TAC levels in the long-term. It also reduced serum TAC levels in urethral use and caused an increase in serum TOC levels with minimal effects on DNA injury and repair. No effect was detected on IL1 α and TNF, but partially reduced the effect on IL-1 β levels. PMID:27803779

[Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities].

PubMed

Xu, Jing; Guo, Chang-jiang; Yang, Ji-jun; Wei, Jing-yu; Li, Yun-feng; Pang, Wei; Jiang, Yu-gang; Cheng, Shuang

2005-03-01

To observe the effects of fruit juices with different antioxidant capacity on antioxidant system function of aged rats. Thirty Wistar rats were randomly divided into three groups: pomegranate juice and apple juice as two experimental groups, while distilled water as normal control group. They were administrated fruit juices or distilled water respectively by gavage daily for 4 weeks. At the end of experiment, the antioxidant system function was assessed. The aged rats in pomegranate juice group showed significantly higher serum antioxidant capacity (0.90 +/- 0.13) mmol/L than that in control group (0.79 +/- 0.10) mmol/L (P < 0.05). The concentrations of serum carbonyl and oxLDL were decreased significantly in pomegranate juice group as compared to the control group (P < 0.05). The percentage of injured blood lymphocyte DNA and the ratio of tail length/total length were declined significantly in pomegranate juice group (P < 0.05 and P < 0.01 respectively). The apple juice showed no effects except decreased ratio of tail length/total length of injured lymphocyte DNA. There were no changes in concentrations of serum vitamin C, vitamin E, urinary 8-OH-dG excretion and the activities of serum SOD, GSH-Px, CAT among three groups. The pomegranate juice should possess higher antioxidant capacity and might improve the antioxidant system function of aged rats, while the apple juice is relatively lower in antioxidant capacity and not very effective. The polyphenols in pomegranate juice might be the important functional components.

A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

PubMed Central

Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

2013-01-01

Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

Potential role of oxidative stress in mediating the effect of altered gravity on the developing rat cerebellum

NASA Astrophysics Data System (ADS)

Sajdel-Sulkowska, Elizabeth M.; Nguon, Kosal; Sulkowski, Zachary L.; Lipinski, Boguslaw

We have previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that exposure to hypergravity results in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. To test this hypothesis we compared cerebellar oxidative stress markers 3-nitrotyrosine (3-NT; an index of oxidative protein modification) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an index of oxidative DNA damage) between stationary control (SC) and rat neonates exposed to 1.65 G (HG) on a 24-ft centrifuge from gestational day (G) 8 to postnatal day (P) 21. The levels of 3-NT and 8-OH-dG were determined by specific ELISAs. We also compared the Purkinje cell number (stereorologically) and rotarod performance between the two groups. The levels of 3-NT were increased only in HG females on P6 and on P12 in the cerebellum, and only in HG females on P12 in the extracellabellar tissue. Limited cerebellar data suggests an increase in the levels of 8-OH-dG on P12 only in HG females. In extracerebellar tissue the increase in 8-OH-dG levels was observed in both HG males and HG females except on P6 when it was only observed in HG males. While preliminary, these data suggest that the effect of hypergravity on the developing brain is sex-dependent and may involve oxidative stress. Oxidative stress may, in turn, contribute to the decrease Purkinje cell number and impaired motor behavior observed in hypergravity-exposed rats.

Higher glucose level and systemic oxidative stress decrease the mean velocity index of the retinal artery during flickering light stimulation in type 1 diabetes.

PubMed

Debelić, Vladimir; Drnovšek Olup, Brigita; Žižek, Bogomir; Skitek, Milan; Jerin, Aleš

2016-10-31

To determine whether higher glucose level and systemic oxidative stress decrease mean velocity (MV) index of the central retinal artery (CRA) during flickering light stimulation in type 1 diabetes (T1D). The study was performed in the period from 2008 to 2015 at the University Eye Clinic in Ljubljana. 41 patients with T1D and 37 participants without diabetes were included. MV in the CRA was measured using Doppler ultrasound diagnostics in basal conditions and during 8 Hz flickering light irritation. The plasma levels of glucose, fructosamine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), triglycerides, cholesterol, and low-density lipoprotein (LDL) were measured. Patients with T1D had significantly higher levels of blood glucose (P<0.001), fructosamine (P<0.001), and 8-OHdG (P<0.001), but there were no significant differences in triglycerides (P=0.108), cholesterol (P=0.531), and LDL (P=0.645) between the groups. Patients with T1D also had a significantly lower MV index in the CRA (1.11±0.15 vs 1.24±0.23; P=0.010). In the T1D group, a significant negative correlation was found between the level of glucose (r=0.58; P<0.001), fructosamine (r=0.46; P=0.003), 8-OHdG (r=0.48; P=0.002) and the MV index in the CRA. At the same time, in this group fructosamine and 8-OHdG levels had a separate effect on the MV index (adjusted R2=0.38, P<0.001). Higher glucose levels, the medium-term glucose level, and systemic oxidative stress could importantly reduce retinal vasodilatation during flickering light irritation in patients with T1D.

DNA damage in children with scoliosis following X-ray exposure.

PubMed

Himmetoglu, S; Guven, M F; Bilsel, N; Dincer, Y

2014-10-14

It has been suggested that cancer incidence is high in subjects with scoliosis who are relatively more often exposed to X--ray for diagnosis and follow--up. X--ray is a kind of ionizing radiation and leads to formation of oxygen free radicals which are capable of damage to DNA, thus altered gen expression and mutation. p53 tumor suppressor gene plays a crucial role in the damage response. It controls the checkpoint of cell cycle and redirects the cell metabolism to either repair of damaged DNA or apoptosis as response to DNA damage. The aim of the present study was to examine serum levels of 8--Hydroxydeoxyguanosine (8--OHdG), a strongly mutagenic product of oxidative DNA damage, p53, superoxide dismutase (SOD) and glutathione peroxidase (G--Px), as antioxidant activity, in children with scoliosis who had got whole spine radiograph two times during the last year. A total of 31 children with adolescent idiopathic scoliosis and age--matched 21 healthy children were included in the study. Serum levels of 8--OHdG and p53 were measured with ELISA kits. SOD and G--Px activities were determined with spectrophotometric assays. Serum levels of 8--OHdG and p53 were found to be higher (P<0.001 and P<0.01, respectively), SOD activity was found to be lower (P<0.001) in the children with scoliosis as compared to age--matched controls. There was no significant difference between the groups for G--Px activity. Our data show that X--ray exposure causes increased 8--OHdG level, and decreased SOD activity, which both may reflect a tumor promoting condition. Increased p53 level may be interpreted as a compensatory effort of cell to X--ray mediated DNA damage.

DNA damage in children with scoliosis following X-ray exposure.

PubMed

Himmetoglu, S; Guven, M F; Bilsel, N; Dincer, Y

2015-06-01

It has been suggested that cancer incidence is high in subjects with scoliosis who are relatively more often exposed to X-ray for diagnosis and follow-up. X-ray is a kind of ionizing radiation and leads to formation of oxygen free radicals which are capable of damage to DNA, thus altered gen expression and mutation. p53 tumor suppressor gene plays a crucial role in the damage response. It controls the checkpoint of cell cycle and redirects the cell metabolism to either repair of damaged DNA or apoptosis as response to DNA damage. The aim of the present study was to examine serum levels of 8-Hydroxydeoxyguanosine (8-OHdG), a strongly mutagenic product of oxidative DNA damage, p53, superoxide dismutase (SOD) and glutathione peroxidase (G-Px), as antioxidant activity, in children with scoliosis who had got whole spine radiograph two times during the last year. A total of 31 children with adolescent idiopathic scoliosis and 21 age-matched healthy children were included in the study. Serum levels of 8-OHdG and p53 were measured with ELISA kits. SOD and G-Px activities were determined with spectrophotometric assays. Serum levels of 8-OHdG and p53 were found to be higher (P<0.001 and P<0.01, respectively), SOD activity was found to be lower (P<0.001) in the children with scoliosis as compared to age-matched controls. There was no significant difference between the groups for G-Px activity. Our data show that X-ray exposure causes increased 8-OHdG level, and decreased SOD activity, which both may reflect a tumor promoting condition. Increased p53 level may be interpreted as a compensatory effort of cell to X-ray mediated DNA damage.

Corticotropin-releasing factor receptor-1 modulates biomarkers of DNA oxidation in Alzheimer’s disease mice

PubMed Central

Zhang, Cheng

2017-01-01

Increased production of hydroxyl radical is the main source of oxidative damage in mammalian DNA that accumulates in Alzheimer’s disease (AD). Reactive oxygen species (ROS) react with both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) to generate 8-hydroxy-2’-deoxyguanosine (8-OHdG), both of which can be measured in the urine. Knowledge of this pathway has positioned measurement of urine 8-OHdG as a reliable index of DNA oxidation and a potential biomarker target for tracking early cellular dysfunction in AD. Furthermore, epigenetic studies demonstrate decreased global DNA methylation levels (e.g. 5-methyl-2’-deoxycytidine, 5-mdC) in AD tissues. Moreover, stress hormones can activate neuronal oxidative stress which will stimulate the release of additional stress hormones and result in damages to hippocampal neurons in the AD brain. Our previous work suggests that treating AD transgenic mice the type-1 corticotropin-releasing factor receptor (CRFR1) antagonist, R121919, to reduce stress signaling, prevented onset of cognitive impairment, synaptic/dendritic loss and Aβ plaque accumulation. Therefore, to investigate whether levels of DNA oxidation can be impacted by the same therapeutic approach, urine levels of hydrogen peroxide, 8-OHdG, 5-mdC and total antioxidant capacity (TAC) were analyzed using an AD Tg mouse model. We found that Tg animals had an 80% increase in hydrogen peroxide levels compared to wild type (Wt) counterparts, an effect that could be dramatically reversed by the chronic administration with R121919. A significant decrease of 8-OHdG levels was observed in Tg mice treated with CRFR1 antagonist. Collectively our data suggest that the beneficial effects of CRFR1 antagonism seen in Tg mice may be mechanistically linked to the modulation of oxidative stress pathways. PMID:28750017

Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.

PubMed

Fedirko, Veronika; Bostick, Roberd M; Long, Qi; Flanders, W Dana; McCullough, Marjorie L; Sidelnikov, Eduard; Daniel, Carrie R; Rutherford, Robin E; Shaukat, Aasma

2010-01-01

The exact antineoplastic effects of calcium and vitamin D(3) in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3) group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D(3) may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D(3) as chemopreventive agents against colorectal neoplasms.

Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia: a novel role of oxidative stress and therapeutic implications.

PubMed

Hamada, Yasuhiro; Fujii, Hideki; Kitazawa, Riko; Yodoi, Junji; Kitazawa, Sohei; Fukagawa, Masafumi

2009-05-01

Diabetes mellitus is associated with increased risk of osteopenia and bone fracture. However, the mechanisms accounting for diabetic bone disorder are unclear. We have previously reported that streptozotocin-induced diabetic mice develop low turnover osteopenia associated with increased oxidative stress in the diabetic condition. To determine the role of oxidative stress in the development of diabetic osteopenia, we presently investigated the effect of overexpression of thioredoxin-1 (TRX), a major intracellular antioxidant, on the development of diabetic osteopenia, using TRX transgenic mice (TRX-Tg). TRX-Tg are C57BL/6 mice that carry the human TRX transgene under the control of beta-actin promoter. Eight-week-old male TRX-Tg mice and wild type (WT) littermates were intraperitoneally injected with either streptozotocin or vehicle. Mice were grouped as 1) non-diabetic WT, 2) non-diabetic TRX-Tg, 3) diabetic WT, and 4) diabetic TRX-Tg. After 12 weeks of streptozotocin treatment, oxidative stress on the whole body and bone was evaluated, and the physical properties of the femora, and histomorphometry parameters of the tibiae were assessed. TRX overexpression did not affect either body weight or hemoglobin A1c levels. There were no significant differences in renal function and in serum levels of calcium, phosphate, and intact parathyroid hormone among the four groups. On the other hand, urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly elevated in diabetic WT and attenuated in diabetic TRX-Tg. Immunohistochemical staining for 8-OHdG revealed marked intensity in the bone tissue of diabetic WT compared with non-diabetic WT, while staining was attenuated in diabetic TRX-Tg. TRX overexpression partially restored reduced bone mineral density and prevented the suppression of bone formation observed in diabetic WT. Increased oxidative stress in diabetic condition contributes to the development of diabetic osteopenia. Suppression of increased oxidative stress by TRX induction could be a potential therapeutic approach for diabetic osteopenia.

Panax ginseng Fraction F3 Extracted by Supercritical Carbon Dioxide Protects against Oxidative Stress in ARPE-19 Cells

PubMed Central

Yang, Chao-Chin; Chen, Chiu-Yuan; Wu, Chun-Chi; Koo, Malcolm; Yu, Zer-Ran; Wang, Be-Jen

2016-01-01

In our previous work, the ethanolic extract of Panax ginseng C. A. Meyer was successively partitioned using supercritical carbon dioxide at pressures in series to yield residue (R), F1, F2, and F3 fractions. Among them, F3 contained the highest deglycosylated ginsenosides and exerted the strongest antioxidant and anti-inflammatory activities. The aim of this study was to investigate the protective effects of P. ginseng fractions against cellular oxidative stress induced by hydrogen peroxide (H2O2). Viability of adult retinal pigment epithelium-19 (ARPE-19) cells was examined after treatments of different concentrations of fractions followed by exposure to H2O2. Oxidative levels (malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reactive oxygen species (ROS)) and levels of activity of antioxidant enzymes were assessed. Results showed that F3 could dose-dependently protected ARPE-19 cells against oxidative injury induced by H2O2. F3 at a level of 1 mg/mL could restore the cell death induced by H2O2 of up to 60% and could alleviate the increase in cellular oxidation (MDA, 8-OHdG, and ROS) induced by H2O2. Moreover, F3 could restore the activities of antioxidant enzymes suppressed by H2O2. In conclusion, F3 obtained using supercritical carbon dioxide fractionation could significantly increase the antioxidant capacity of P. ginseng extract. The antioxidant capacity was highly correlated with the concentration of F3. PMID:27754362

Autoxidation and toxicant-induced oxidation of lipid and DNA in monkey liver: reduction of molecular damage by melatonin.

PubMed

Cabrer, J; Burkhardt, S; Tan, D X; Manchester, L C; Karbownik, M; Reiter, R J

2001-11-01

Melatonin, the main secretory product of the pineal gland, is a free radical scavenger and antioxidant which protects against oxidative damage due to a variety of toxicants. However, there is little information regarding melatonin's antioxidative capacity in tissues of primates. In this study we examined the protective effects of melatonin in monkey liver homogenates against lipid damage that occurred as a result of autoxidation or that induced by exogenous addition of H202 and ferrous iron (Fe2+). Additionally, we tested melatonin's protective effect against oxidative damage to DNA induced by chromium(III) (CrIII) plus H202. The levels of malondialdehyde and 4-hydroxyalkenals were assayed as an index of lipid peroxidation, and the concentrations of 8-hydroxydeoxyguanosine (8-OHdG) as an endpoint of oxidative DNA damage. The increases in malondialdehyde+4-hydroxyalkenals concentrations as a consequence of autoxidation or after the addition of H202 plus Fe2+ to the homogenates were time-dependent. The accumulation of these damaged products due to either auto-oxidative processes or induced by H202 and Fe2+ were significantly reduced by melatonin in a concentration-dependent-manner. The levels of 8-OHdG were elevated in purified monkey liver DNA incubated with a combination of CrCl3 plus H2O2. This rise in oxidatively damaged DNA was prevented by 10 microM concentration of melatonin. Also, melatonin reduced the damage to DNA that was caused by auto-oxidative processes. These findings in monkey liver tissue document the ability of melatonin to protect against oxidative damage to both lipid and DNA in primate tissue, as observed previously in rodent tissue. The findings provide support for the use of melatonin as suitable agent to reduce damage inflicted by free radical species in primates.

Oxidative stress and triglycerides as predictors of subclinical atherosclerosis in prediabetes.

PubMed

Al-Aubaidy, Hayder A; Jelinek, Herbert F

2014-03-01

The role of triglycerides in early preclinical atherosclerosis is controversial. Antioxidant markers may be associated with triglyceride levels in early preclinical atherosclerosis especially when fasting plasma glucose is raised. This cross-sectional study included 127 participants attending the Diabetes Screening Clinic, Charles Sturt University, Australia. Serum 8-hydroxy-2-deoxy-guanosine (8-OHdG) was significantly greater in the impaired fasting glucose (IFG) group compared with the control group (536.7 pg/ml ± 249.8 versus 171.4 pg/ml ± 96.9, respectively). The increase in 8-OHdG was associated with a mildly non-significant elevation in low-density lipoprotein level (3.2 ± 1.1 mmol/l) and a poor level of high-density lipoprotein (1.31 ± 0.3 mmol/l) in the IFG group. However, a significant increase in triglycerides (1.6 ± 0.97 mmol/l; P < 0.05) in the IFG group was observed. Erythrocyte reduced glutathione (GSH) levels in the IFG group, although increased, were also not significantly different to control. A significant increase in 8-OHdG is associated with increased levels of triglycerides in the absence of significant changes in reduced GSH and normal levels of cholesterol in the IFG cohort, suggesting that oxidative stress may be present and indicative of subclinical atherosclerosis.

Nitrative Stress and Tau Accumulation in Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) in the Kii Peninsula, Japan

PubMed Central

Hata, Yukiko; Ma, Ning; Yoneda, Misao; Morimoto, Satoru; Okano, Hideyuki; Murayama, Shigeo; Kawanishi, Shosuke; Kuzuhara, Shigeki; Kokubo, Yasumasa

2018-01-01

Objective: The Kii Peninsula of Japan is known to be a high incidence area of amyotrophic lateral sclerosis/parkinsonism-dementia complex (Kii ALS/PDC) with tauopathy. Nitrative stress and oxidative stress on ALS/PDC and their relationship to tau pathology were clarified. Methods: Seven patients with Kii ALS/PDC (3 males and 4 females, average age 70.7 years, 3 with ALS, 2 with ALS with dementia, and 2 with PDC) were analyzed in this study. Five patients with Alzheimer's disease and five normal aged subjects were used as controls. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded temporal lobe sections (the hippocampal area including hippocampus, prosubiculum, subiculum, presubiculum, and parahippocampal gyri) using antibodies to detect phosphorylated tau (anti-AT-8), nitrated guanine (anti-8-NG), anti-iNOS, anti-NFκB, and oxidized guanine (anti-8-OHdG) antibodies. Results: Most hippocampal neurons of Kii ALS/PDC patients were stained with anti-8-NG, anti-iNOS, anti-NFκB, and anti-8-OHdG antibodies and some AT-8 positive neurons were co-stained with anti-8-NG antibody. The numbers of 8-NG positive neurons and 8-OHdG positive neurons were greater than AT-8 positive neurons and the number of 8-NG positive neurons was larger in patients with Kii ALS/PDC than in controls. Conclusion: Nitrative and oxidative stress may take priority over tau accumulation and lead to the neurodegeneration in Kii ALS/PDC. PMID:29403345

Nitrative Stress and Tau Accumulation in Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) in the Kii Peninsula, Japan.

PubMed

Hata, Yukiko; Ma, Ning; Yoneda, Misao; Morimoto, Satoru; Okano, Hideyuki; Murayama, Shigeo; Kawanishi, Shosuke; Kuzuhara, Shigeki; Kokubo, Yasumasa

2017-01-01

Objective: The Kii Peninsula of Japan is known to be a high incidence area of amyotrophic lateral sclerosis/parkinsonism-dementia complex (Kii ALS/PDC) with tauopathy. Nitrative stress and oxidative stress on ALS/PDC and their relationship to tau pathology were clarified. Methods: Seven patients with Kii ALS/PDC (3 males and 4 females, average age 70.7 years, 3 with ALS, 2 with ALS with dementia, and 2 with PDC) were analyzed in this study. Five patients with Alzheimer's disease and five normal aged subjects were used as controls. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded temporal lobe sections (the hippocampal area including hippocampus, prosubiculum, subiculum, presubiculum, and parahippocampal gyri) using antibodies to detect phosphorylated tau (anti-AT-8), nitrated guanine (anti-8-NG), anti-iNOS, anti-NFκB, and oxidized guanine (anti-8-OHdG) antibodies. Results: Most hippocampal neurons of Kii ALS/PDC patients were stained with anti-8-NG, anti-iNOS, anti-NFκB, and anti-8-OHdG antibodies and some AT-8 positive neurons were co-stained with anti-8-NG antibody. The numbers of 8-NG positive neurons and 8-OHdG positive neurons were greater than AT-8 positive neurons and the number of 8-NG positive neurons was larger in patients with Kii ALS/PDC than in controls. Conclusion: Nitrative and oxidative stress may take priority over tau accumulation and lead to the neurodegeneration in Kii ALS/PDC.

Astaxanthin inhibits thrombosis in cerebral vessels of stroke-prone spontaneously hypertensive rats.

PubMed

Sasaki, Yasuto; Kobara, Nozomi; Higashino, Saori; Giddings, John C; Yamamoto, Junichiro

2011-10-01

It is known that vitamin E and some carotenoids have antioxidant activities that alleviate endothelial dysfunction and play a protective role against cardiovascular disease. The current study was designed to examine the hypothesis that astaxanthin, a red pigment carotenoid found in salmonid and crustacean aquaculture, protects stroke-prone spontaneously hypertensive rats (SHRSP) from vascular oxidative damage, hypertension, and cerebral thrombosis. Male 6-week-old SHRSP were classified into 4 groups: a control group, 2 astaxanthin groups, and a vitamin E group. The treated animals were given either astaxanthin or vitamin E for 3 weeks. Body weights in each group were not significantly different from control group during the treatment period, but the usual increase in systolic blood pressure in SHRSP observed with age was significantly suppressed by treatment. Thrombogenesis, assessed using a helium-neon (He-Ne) laser technique in pial blood vessels, together with antioxidant activity, assessed by measuring urinary 8-OHdG levels, were significantly moderated. Urinary nitric oxide (NO) metabolites were increased after treatment. These results supported our hypothesis and strongly suggested that the antithrombotic and antihypertensive effects of astaxanthin or vitamin E may be related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species. Copyright © 2011 Elsevier Inc. All rights reserved.

The cost of reproduction in women: Reproductive effort and oxidative stress in premenopausal and postmenopausal American women.

PubMed

Ziomkiewicz, Anna; Frumkin, Amara; Zhang, Yawei; Sancilio, Amelia; Bribiescas, Richard G

2018-01-01

Life history theory predicts a trade-off between female investment in reproduction and somatic maintenance, which can result in accelerated senescence. Oxidative stress has been shown to be a causal physiological mechanism for accelerated aging and a possible contributor to this trade-off. We aimed to test the hypothesis for the existence of significant associations between measures of reproductive effort and the level of oxidative stress biomarkers in premenopausal and postmenopausal American women. Serum samples and questionnaire data were collected from 63 premenopausal and postmenopausal women (mean age 53.4 years), controls in the Connecticut Thyroid Health Study, between May 2010 and December 2013. Samples were analyzed for levels of 8-OHdG and Cu/Zn-SOD using immunoassay method. Levels of oxidative damage (8-OHdG) but not oxidative defense (Cu/Zn-SOD) were negatively associated with parity and number of sons in premenopausal women (r = -0.52 for parity, r = -0.52 for number of sons, P < .01). Together, measures of reproductive effort, women's BMI, age, and menopausal status explained around 15% of variance in level of 8-OHdG. No association between reproductive effort characteristics and oxidative damage was found for postmenopausal women. We found no evidence of a trade-off between somatic maintenance as measured by 8-OHdG and reproductive effort in women from this American population. On the contrary, higher gravidity and parity in premenopausal women was associated with lower damage to cellular DNA caused by oxidative stress. These results highlight the importance of population variation and environmental conditions when testing the occurrence of life-history trade-offs. © 2017 Wiley Periodicals, Inc.

Higher glucose level and systemic oxidative stress decrease the mean velocity index of the retinal artery during flickering light stimulation in type 1 diabetes

PubMed Central

Debelić, Vladimir; Drnovšek Olup, Brigita; Žižek, Bogomir; Skitek, Milan; Jerin, Aleš

2016-01-01

Aim To determine whether higher glucose level and systemic oxidative stress decrease mean velocity (MV) index of the central retinal artery (CRA) during flickering light stimulation in type 1 diabetes (T1D). Methods The study was performed in the period from 2008 to 2015 at the University Eye Clinic in Ljubljana. 41 patients with T1D and 37 participants without diabetes were included. MV in the CRA was measured using Doppler ultrasound diagnostics in basal conditions and during 8 Hz flickering light irritation. The plasma levels of glucose, fructosamine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), triglycerides, cholesterol, and low-density lipoprotein (LDL) were measured. Results Patients with T1D had significantly higher levels of blood glucose (P < 0.001), fructosamine (P < 0.001), and 8-OHdG (P < 0.001), but there were no significant differences in triglycerides (P = 0.108), cholesterol (P = 0.531), and LDL (P = 0.645) between the groups. Patients with T1D also had a significantly lower MV index in the CRA (1.11 ± 0.15 vs 1.24 ± 0.23; P = 0.010). In the T1D group, a significant negative correlation was found between the level of glucose (r = −0.58; P < 0.001), fructosamine (r = −0.46; P = 0.003), 8-OHdG (r = −0.48; P = 0.002) and the MV index in the CRA. At the same time, in this group fructosamine and 8-OHdG levels had a separate effect on the MV index (adjusted R2 = 0.38, P < 0.001). Conclusion Higher glucose levels, the medium-term glucose level, and systemic oxidative stress could importantly reduce retinal vasodilatation during flickering light irritation in patients with T1D. PMID:27815934

Differential Gene Susceptibility to Sperm DNA Damage: Analysis of Developmental Key Genes in Trout

PubMed Central

González-Rojo, Silvia; Fernández-Díez, Cristina; Guerra, Susana M.; Robles, Vanesa; Herraez, Maria Paz

2014-01-01

Sperm chromatin in mammals is packaged in different blocks associated to protamines (PDNA), histones (HDNA), or nuclear matrix proteins. Differential packaging has been related to early or late transcription and also to differential susceptibility to genotoxic damage. Genes located in the more accessible HDNA could be more susceptible to injuries than those located in PDNA, being potential biomarkers of paternal DNA damage. Fish sperm chromatin organization is much diversified, some species lacking protamines and some others totally depleted of histones. Analyzing genotoxic damage in a species homogeneously compacted with some sperm nuclear basic protein type, could help in deciphering the clues of differential susceptibility to damage. In the present study we analyzed in rainbow trout the differential susceptibility of nine genes to UV irradiation and H2O2 treatment. The absence of histones in the sperm nuclei was confirmed by Western blot. The chromatin fractionation in sensitive and resistant regions to PvuII (presumably HDNA-like and PDNA-like, respectively) revealed that the nine genes locate in the same resistant region. The number of lesions promoted was quantified using a qPCR approach. Location of 8-hydroxyguanosine (8-OHdG) was analyzed by immunocytochemistry and confocal microscopy. UV irradiation promoted similar number of lesions in all the analyzed genes and a homogenous distribution of 8-OHdG within the nuclei. 8-OHdG was located in the peripheral area of the nucleus after H2O2 treatment, which promoted a significantly higher number of lesions in developmental-related genes (8.76–10.95 lesions/10 kb) than in rDNA genes (1.05–1.67 lesions/10 kb). We showed for the first time, that differential susceptibility to damage is dependent on the genotoxic mechanism and relies on positional differences between genes. Sensitive genes were also analyzed in cryopreserved sperm showing a lower number of lesions than the previous treatments and a predominant peripheral distribution of oxidative damage (8-OHdG). PMID:25479606

Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson's Disease-Associated LRRK2 Gene Mutations.

PubMed

Loeffler, David A; Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

2017-01-01

Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most frequent cause of inherited Parkinson's disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro . We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients ( LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations ( LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated LRRK2 mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD.

Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson’s Disease-Associated LRRK2 Gene Mutations

PubMed Central

Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.; LeWitt, Peter A.

2017-01-01

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of inherited Parkinson’s disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro. We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients (LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations (LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated LRRK2 mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD. PMID:28420983

Increased penile expression of transforming growth factor and elevated systemic oxidative stress in rabbits with chronic partial bladder outlet obstruction.

PubMed

Lin, W-Y; Chang, P-J; Lin, Y-P; Wu, S-B; Chen, C-S; Levin, R M; Wei, Y-H

2012-02-01

There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-β1 (TGF-β1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-β1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-β1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-β1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Early-life exposure to air pollutants and adverse pregnancy outcomes: protocol for a prospective cohort study in Beijing

PubMed Central

Song, Jing; Wei, Ling; Ma, Ying; Tian, Ning; Huang, Shi Yun; Dai, Yin Mei; Zhao, Li Hong; Kong, Yuan Yuan

2017-01-01

Introduction The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. Methods and analysis Here, 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. Ethics and dissemination This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. Trial registration number This study has been registered in WHO International Clinical Trial Register—Chinese Clinical Trial Registry under registration number ChiCTR-ROC-16010181 (http :// www.chictr.org.cn / showproj.aspx ?proj=17328). PMID:28871018

Determining median urinary iodine concentration that indicates adequate iodine intake at population level.

PubMed Central

Delange, François; de Benoist, Bruno; Burgi, Hans

2002-01-01

OBJECTIVE: Urinary iodine concentration is the prime indicator of nutritional iodine status and is used to evaluate population-based iodine supplementation. In 1994, WHO, UNICEF and ICCIDD recommended median urinary iodine concentrations for populations of 100- 200 micro g/l, assuming the 100 micro g/l threshold would limit concentrations <50 micro g/l to 100 micro g/l. The total population was 55 892, including 35 661 (64%) schoolchildren. Median urinary iodine concentrations were 111-540 (median 201) micro g/l for all populations, 100-199 micro g/l in 23 (48%) populations and >/=200 micro g/l in 25 (52%). The frequencies of values <50 micro g/l were 0-20.8 (mean 4.8%) overall and 7.2% and 2.5% in populations with medians of 100-199 micro g/l and >200 micro g/l, respectively. The frequency reached 20% only in two places where iodine had been supplemented for <2 years. CONCLUSION: The frequency of urinary iodine concentrations <50 micro g/l in populations with median urinary iodine concentrations >/=100 micro g/l has been overestimated. The threshold of 100 micro g/l does not need to be increased. In populations, median urinary iodine concentrations of 100-200 micro g/l indicate adequate iodine intake and optimal iodine nutrition. PMID:12219154

Periodic monitoring of persistent organic pollutants and molecular damage in Cyprinus carpio from Büyük Menderes River.

PubMed

Çağdaş, Beste; Kocagöz, Rasih; Onat, İlgen; Perçin, Fatih; Özaydın, Okan; Orhan, Hilmi

2017-02-01

Concentrations of persistent organic pollutants (POPs) were quantified in river water and sediment, as well as in the liver and muscle tissues of Cyprinus carpio that were sampled four times in a year at three stations in the Büyük Menderes River (BMR). Potential biomarkers of possible cellular molecular damage, namely lipid peroxidation (LPO) degradation products, protein carbonyls (PCO) and DNA repair product 8-hydroxy-2'-deoxyguanosine (8-OHdG), were analysed. All the targeted pollutants were measurable both in biotic and abiotic samples. Interestingly, the results suggested that there was recent organochlorine pesticide (OCP) input into the river water in the first two sampling periods in all stations in contrast to prohibition, while input of polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) was not detected. Liver POP concentrations were higher than in muscle, as expected, and were found to decrease from the first to the fourth sampling period in all stations, except PBDEs. Levels of LPO degradation products in the liver and in muscle tissues decreased from the first to the fourth sampling period. This suggests that these markers reflect the lipid damage in respective tissues due to the tissue burden of targeted POPs. Protein carbonyls were the highest in the first sampling period, followed by a dramatic decrease in the second, and then a gradual increase towards the fourth sampling period in all stations. 8-OHdG levels were lower in Sarayköy station in the first sampling period. Among the measured biomarkers, only several LPO degradation products were significantly correlated with OCPs and PCBs in liver tissue.

Levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by Epstein-Barr virus.

PubMed

Jakovljevic, A; Andric, M; Nikolic, N; Coric, V; Krezovic, S; Carkic, J; Knezevic, A; Beljic-Ivanovic, K; Pljesa-Ercegovac, M; Miletic, M; Soldatovic, I; Radosavljevic, T; Jovanovic, T; Simic, T; Ivanovic, V; Milasin, J

2018-06-01

To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)] and bone resorption regulators [receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)] compared to EBV-negative periapical lesions and healthy pulp tissues. The experimental group consisted of 30 EBV-positive and 30 EBV-negative periapical lesions collected in conjunction with apicoectomy. The pulp tissues of 20 impacted third molars were used as healthy controls. The qualitative and quantitative analysis of EBV was performed by nested and real-time polymerase chain reaction (PCR), respectively. The levels of RANKL and OPG were analysed by reverse transcriptase real-time PCR. The levels of 8-OHdG and GSSG were determined by enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U-test and Spearman's correlation were used for statistical analysis. The levels of RANKL, OPG, 8-OHdG and GSSG were significantly higher in apical periodontitis lesions compared to healthy pulp controls (P = 0.001, P < 0.001, P < 0.001 and P < 0.05, respectively). RANKL and OPG mRNA expression was significantly higher in EBV-positive compared to EBV-negative periapical lesions (P < 0.05). There was no significant correlation between EBV copy numbers and levels of RANKL, OPG, 8OH-dG and GSSG in apical periodontitis. Levels of bone resorption regulators and oxidative stress biomarkers were increased in apical periodontitis compared to healthy pulp tissues. EBV-positive periapical lesions exhibited higher levels of RANKL and OPG compared to EBV-negative periapical lesions. EBV may contribute to progression of apical periodontitis via enhanced production of bone resorption regulators. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Increased 8-hydroxy-2'-deoxyguanosine in plasma and decreased mRNA expression of human 8-oxoguanine DNA glycosylase 1, anti-oxidant enzymes, mitochondrial biogenesis-related proteins and glycolytic enzymes in leucocytes in patients with systemic lupus erythematosus.

PubMed

Lee, H-T; Lin, C-S; Lee, C-S; Tsai, C-Y; Wei, Y-H

2014-04-01

We measured plasma levels of the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and leucocyte mRNA expression levels of the genes encoding the 8-OHdG repair enzyme human 8-oxoguanine DNA glycosylase 1 (hOGG1), the anti-oxidant enzymes copper/zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase-1 (GPx-1), GPx-4, glutathione reductase (GR) and glutathione synthetase (GS), the mitochondrial biogenesis-related proteins mtDNA-encoded ND 1 polypeptide (ND1), ND6, ATPase 6, mitochondrial transcription factor A (Tfam), nuclear respiratory factor 1(NRF-1), pyruvate dehydrogenase E1 component alpha subunit (PDHA1), pyruvate dehydrogenase kinase isoenzyme 1 (PDK-1) and hypoxia inducible factor-1α (HIF-1α) and the glycolytic enzymes hexokinase-II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase A (LDHa). We analysed their relevance to oxidative damage in 85 systemic lupus erythematosus (SLE) patients, four complicated SLE patients undergoing rituximab treatment and 45 healthy individuals. SLE patients had higher plasma 8-OHdG levels (P < 0·01) but lower leucocyte expression of the genes encoding hOGG1(P < 0·01), anti-oxidant enzymes (P < 0·05), mitochondrial biogenesis-related proteins (P < 0·05) and glycolytic enzymes (P < 0·05) than healthy individuals. The increase in plasma 8-OHdG was correlated positively with the elevation of leucocyte expression of the genes encoding hOGG1 (P < 0·05), anti-oxidant enzymes (P < 0·05), several mitochondrial biogenesis-related proteins (P < 0·05) and glycolytic enzymes (P < 0·05) in lupus patients. The patients, whose leucocyte mtDNA harboured D310 heteroplasmy, exhibited a positive correlation between the mtDNA copy number and expression of ND1, ND6 and ATPase 6 (P < 0·05) and a negative correlation between mtDNA copy number and systemic lupus erythematosus disease activity index (SLEDAI) (P < 0·05), as well as plasma 8-OHdG (P < 0·05). In particular, four complicated SLE patients with increased expression of the genes encoding the anti-oxidant enzymes, GAPDH, Tfam and PDHA1, experienced better therapeutic outcomes after rituximab therapy. In conclusion, higher oxidative damage with suboptimal increases in DNA repair, anti-oxidant capacity, mitochondrial biogenesis and glucose metabolism may be implicated in SLE deterioration, and this impairment might be improved by targeted biological therapy. © 2013 British Society for Immunology.

Formaldehyde and co-exposure with benzene induce compensation of bone marrow and hematopoietic stem/progenitor cells in BALB/c mice during post-exposure period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Chenxi

Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3 mg/m{sup 3} FA for 2 weeks, mimicking occupational exposure, and were monitored for another 7 days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrowmore » cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk. - Highlights: • Nucleated bone marrow cell count recovered after 7 days post-FA and/or BZ exposure. • CFU-GM showed an increase in colonies and 8-OHdG after 7 days post-FA + BZ exposure. • Levels of ROS in CFU-GM and BFU-E were increased by FA or FA + BZ during recovery. • Levels of GM-CSF and EPOR were suppressed after 7 days post-FA or FA + BZ exposure. • Co-exposure was more potent for some endpoints and may pose a greater leukemia risk.« less

Increased DNA damage and increased apoptosis and necrosis in patients with severe sepsis and septic shock.

PubMed

Bahar, Ilhan; Elay, Gülseren; Başkol, Gulden; Sungur, Murat; Donmez-Altuntas, Hamiyet

2018-02-01

Reactive oxygen species (ROS) has a key role in the pathogenesis of sepsis. We wanted to evaluate ROS-associated lymphocyte necrosis and apoptosis. A total of 51 patients were included in the study, 29 in the patient group and 22 in the control group. Blood samples were taken from patients in the patient group during severe sepsis or septic shock, then again once they had recovered. Oxidative DNA damage was evaluated by 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Peripheral blood lymphocytes from patients were evaluated with a microscope immediately. The rate of apoptosis and necrosis of lymphocytes were evaluated according to the number of cells in the peripheral. The level of 8-OHdG increased with severe sepsis or septic shock. There were significant differences between the pre- and post-treatment values for apoptotic cell frequency (4.21±3.15 vs. 3.82±3.07, P<0.05) and necrotic cell frequency (4.75±3.61 vs. 4.09±3.37, P<0.05). Apoptosis and necrosis was increased during severe sepsis and septic shock, and apoptosis increase also continued after recovery, but necrosis decreased following disease recovery. CONCLUSıONS: In patients with severe sepsis or septic shock, apoptosis and necrosis were increased along with increased 8-OHdG level. Copyright © 2017 Elsevier Inc. All rights reserved.

Synergistic interaction between excess hepatic iron and alcohol ingestion in hepatic mutagenesis.

PubMed

Asare, George A; Bronz, Michelle; Naidoo, Vivash; Kew, Michael C

2008-12-05

Hereditary hemochromatosis (HH) and dietary iron overload are the main iron-loading diseases. Fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are complications to HH and dietary iron overload possibly influenced by co-factors. Alcohol may be one such factor. The aim therefore was to determine the extent of synergistic interaction between free hepatic iron and alcohol, complicating dietary iron overload in HCC pathogenesis. Four groups of 20 Wistar albino rats were used: group 1 (C) was fed the chow diet; group 2 (Fe) was supplemented with 0.75% ferrocene iron; group 3 (Fe+Al), 0.75% iron and 7% ethanol; and group 4, 7% ethanol (Al) for 12 months. Iron profile, superoxide/nitrite free radicals, lipid peroxidation (LPO)/8-isoprostane (8-IP), 8-hydroxydeoxyguanosine (8-OHdG), oxidative lipid/DNA damage immunohistochemistry, transaminases (AST/ALT) and Ames mutagenesis tests were performed. Significant differences were observed in the Fe+Al group for LPO, 8-IP, AST and ALT (p<0.001, 0.001, 0.001 and 0.001, respectively) compared to other groups. A three-fold synergistic interaction was observed for the same parameters. Furthermore, significant differences of p<0.05 and 0.001 were observed for 8-OHdG and mutagenesis, respectively, with an additive synergy in the Fe+Al group. ALT/8-OHdG and ALT/mutagenesis correlated positively (p<0.04 and 0.008, respectively). The immunohistochemistry revealed iron/alcohol multiplicative synergism with hydroxyl radical involvement. Mutagenic effects of iron and alcohol are synergistically multiplicative implicating hydroxyl free radicals in hepatocarcingenesis.

Effects of Dietary Supplementation of Oregano Essential Oil to Sows on Oxidative Stress Status, Lactation Feed Intake of Sows, and Piglet Performance

PubMed Central

Tan, Chengquan; Sun, Haiqing; Ao, Jiangtao; Long, Guang; Jiang, Siwen; Peng, Jian

2015-01-01

Fifty-four multiparous large white sows were used to determine the effects of supplementing oregano essential oil (OEO) to the gestation and lactation diets on oxidative stress status, lactation feed intake, and their piglet performance. Two groups were fed diets with (OEO; n = 28) or without (Control; n = 26) supplemental 15 mg/kg OEO during gestation and lactation. The serum levels of reactive oxygen species (ROS) (P < 0.05), 8-hydroxy-deoxyguanosine (8-OHdG) (P < 0.05), and thiobarbituric acid reactive substances (TBARS) (P < 0.05) were higher during gestation (days 90 and 109) and lactation (days 1 and 3) than in early gestation (day 10). Compared with the control group, the OEO diet significantly reduced sows' serum concentrations of 8-OHdG (P < 0.05) and TBARS (P < 0.01) on day 1 of lactation. The OEO diet increased the sows' counts of faecal lactobacillus (P < 0.001) while reducing Escherichia coli (P < 0.001) and Enterococcus (P < 0.001). In the third week of lactation the treatment tended to increase sow's feed intake (P = 0.07), which resulted in higher average daily gain (P < 0.01) of piglets. Our results demonstrated that there is an increased systemic oxidative stress during late gestation and early lactation of sows. The OEO supplementation to sows' diet improved performance of their piglets, which may be attributed to the reduced oxidative stress. PMID:26539506

Impact of pH on Urine Chemistry Assayed on Roche Analyzers.

PubMed

Cohen, R; Alkouri, R; Tostivint, I; Djiavoudine, S; Mestari, F; Dever, S; Atlan, G; Devilliers, C; Imbert-Bismut, F; Bonnefont-Rousselot, D; Monneret, D

2017-10-01

The pH may impact the concentration of certain urinary parameters, making urine pre-treatment questionable. 1) Determining the impact of pH in vitro on the urinary concentration of chemistry parameters assayed on Roche Modular analyzers. 2) Evaluating whether concentrations depended on pH in non-pretreated urines from patients. 1) The optimal urinary pH values for each measurement were: 6.3 ± 0.8 (amylase), < 5.5 (calcium and magnesium), < 6.5 (phosphorus), > 6.5 (uric acid). Urinary creatinine, sodium and urea concentrations were not pH-dependent. 2) In urines from patients, the pH was negatively associated with the concentration of some urinary parameters. However, concentrations of all the parameters were strongly and positively correlated with urinary creatinine, and relationships with pH were no longer evidenced after creatinine-normalization. The need for urine pH adjustment does not seem necessary when considering renal function. However, from an analytical and accreditation standpoint, the relationship between urine pH and several parameters justifies its measurement.

Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure

PubMed Central

2012-01-01

Background Angiotensin receptor blockers (ARBs) are reported to provide direct protection to many organs by controlling inflammation and decreasing oxidant stress in patients without arteriosclerosis. This study aimed to evaluate (1) whether an ARB (candesartan) decreases values for inflammatory parameters in hypertensive patients with type 2 diabetes mellitus of long duration accompanied by arteriosclerosis and (2) whether there any predictors of which patients would receive the benefits of organ protection by candesartan. Methods We administered candesartan therapy (12 mg daily) for 6 months and evaluated whether there was improvement in serum inflammatory parameters high molecular weight adiponectin (HMW-ADN), plasminogen activator inhibitor-1 (PAI-1), highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) in serum and urinary-8-hydroxydeoxyguanosine (U-8-OHdG). We then analyzed the relationship between the degree of lowering of blood pressure and inflammatory factors and the relationship between pulse pressure and inflammatory factors. Finally, we analyzed predictive factors in patients who received the protective benefit of candesartan. Results After 6 months of treatment, significant improvements from baseline values were observed in all patients in HMW-ADN and PAI-1 but not in Hs-CRP, VCAM-1 and U-8-OHdG. Multilinear regression analysis was performed to determine which factors could best predict changes in HMW-ADN and PAI-1. Changes in blood pressure were not significant predictors of changes in metabolic factors in all patients. We found that the group with baseline pulse pressure <60 mmHg had improved HMW-ADN and PAI-1 values compared with the group with baseline pulse pressure ≥ 60 mmHg. These results suggest that pulse pressure at baseline could be predictive of changes in HMW-ADN and PAI-1. Conclusions Candesartan improved inflammatory parameters (HMW-ADN and PAI-1) in hypertensive patients with type 2 diabetes mellitus of long duration independent of blood pressure changes. Patients with pulse pressure <60 mmHg might receive protective benefits by candesartan. Trial registration UMIN000007921 PMID:23034088

Iodine deficiency in Saudi Arabia.

PubMed

Al-Nuaim, A R; Al-Mazrou, Y; Kamel, M; Al-Attas, O; Al-Daghari, N; Sulimani, R

1997-05-01

Data on the status of iodine deficiency in the Arabian peninsula is scarce. We have conducted a cross-sectional national epidemiological survey in Saudi Arabia to study the iodine status of Saudi schoolchildren, between eight and ten years, who were randomly selected, after taking into consideration the gender, provincial population and area distribution. Casual urine samples were collected and sent to the central laboratory for analysis. Clinical assessment for the presence of goiter was conducted in four areas with different geographical natures. The survey included 4638 subjects, and their median and mean (SD) of urinary iodine concentration was 18 and 17 m g/dL, respectively. We found provincial differences with respect to urinary iodine concentration and the percentage of subjects with urinary iodine concentration <10 m g/dL. The Southern province had the lowest median (11 m g/dL) and the highest percentage (45%) of subjects with urinary iodine concentration <10 m g/dL. On the other hand, subjects of the Western province had the highest median (24 m g/dL) and the lowest percentage (8%) of subjects with urinary iodine concentration <10 m g/dL. The clinical assessment revealed that the highest prevalence and more advanced grade of goiter (22%, 95% CI 19-25, grade 1; 8%, 95% CI 6-10, grade 2) was found in the Asir region, a high-altitude area in the Southern province. The lowest prevalence of goiter (4%, 95% CI 0.8-7.2, grade 1) was found in Gizan, an urban coastal community. There was a significant relationship between the prevalence of goiter and the urinary iodine concentration. The survey for iodine deficiency disorder (IDD) in Saudi Arabia has shown a mild degree of iodine deficiency in the Southern province. Odds ratio (OR) was used to study the statistical relationship between the prevalence of goiter and the urinary iodine concentration. There is a need to launch a control program to ensure the exclusive availability of iodized salt in Saudi Arabia, especially in the Southern province.

Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

PubMed

Longo-Mbenza, Benjamin; Mvitu Muaka, Moise; Masamba, Wayiza; Muizila Kini, Lucien; Longo Phemba, Igor; Kibokela Ndembe, Dalida; Tulomba Mona, Doris

2014-01-01

To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM.

Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

PubMed Central

Longo-Mbenza, Benjamin; Mvitu Muaka, Moise; Masamba, Wayiza; Muizila Kini, Lucien; Longo Phemba, Igor; Kibokela Ndembe, Dalida; Tulomba Mona, Doris

2014-01-01

AIM To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. METHODS We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). RESULTS The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. CONCLUSION Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM. PMID:24790873

Urinary Concentrations of Triclosan, Benzophenone-3, and Bisphenol A in Taiwanese Children and Adolescents

PubMed Central

Chang, Fu-Kuei; Shiea, Jentaie; Tsai, Hsin-Jen

2017-01-01

The purpose of this study was to determine the levels of urinary triclosan (TCS), benzophenone-3 (BP-3), and bisphenol A (BPA) in 52 children and 71 adolescents. The effects of age and sex on the levels of urinary TCS, BP-3, and BPA were explored, respectively. Results demonstrated the overall detection rates of urinary TCS, BP-3, and BPA were 18.7%, 8.1%, and 49.6%, respectively. The females had higher TCS concentrations than males (p = 0.051). The detection rate of urinary BP-3 in females (12.3%) was higher than that in males (0%) (p = 0.015). Moreover, the detection rate of urinary BP-3 in adolescents (14.1%) was higher than that in children (0%) (p = 0.005). For children, no urinary BP-3 was found. There were no differences in detection rates and concentrations of urinary TCS, BP-3, and BPA between males and females, respectively. For adolescents, urinary BP-3 was only found in the females. Urinary TCS levels in females were higher than those in males (p = 0.047). The present study showed that urinary TCS concentrations in females were significantly higher than those in males, respectively. In addition, BP-3 was only detected in urine samples of female adolescents. Sex and age were the important factors influencing urinary TCS and BP-3 concentrations. PMID:29232866

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh.

PubMed

Hata, Akihisa; Yamanaka, Kenzo; Habib, Mohamed Ahsan; Endo, Yoko; Fujitani, Noboru; Endo, Ginji

2012-05-01

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content. The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry. The median iAs concentration in drinking water was 55 μgAs/L (range <0.5-332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7-32.3), 1.8 (<0.5-3.3), 13.7 (5.6-25.0), and 88.6 μgAs/L (47.9-153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water. All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.

Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Cohen, Samuel M

2009-06-30

Arsenite (As(III)), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS, therefore, we investigated the ability of apocynin (acetovanillone), an NADPH oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in reducing the cytotoxicity of As(III) and dimethylarsinous acid (DMA(III)) in rat urothelial cells in vitro. When tested at the same concentrations as apocynin, other antioxidants, such as l-ascorbate and N-acetylcysteine, did not inhibit As(III)-induced cytotoxicity but they were more effective at inhibiting DMA(III)-induced cytotoxicity compared with apocynin. In vivo, female rats were treated for 3 weeks with 100ppm As(III). Immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially induced by As(III) treatment on rat urothelium, and significantly reduced the cytotoxicity of superficial cells detected by scanning electron microscopy (SEM). However, based on the incidence of simple hyperplasia and the bromodeoxyuridine (BrdU) labeling index, apocynin did not inhibit As(III)-induced urothelial cell proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may have the ability to partially inhibit arsenic-induced oxidative stress and cytotoxicity of the rat bladder epithelium in vitro and in vivo. However, apocynin did not inhibit the regenerative cell proliferation induced by arsenite in a short-term study.

Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Chen, Baowei; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

2012-09-28

Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100 ppm As(V). DMPS (2800 ppm) co-administered in the diet significantly reduced the As(V)-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA. Copyright © 2012. Published by Elsevier Ireland Ltd.

Effects of administration of beta-carotene, ascorbic acid, persimmons, and pods on antioxidative ability in UV-irradiated ODS rats.

PubMed

Hosotani, Keisuke; Yoshida, Minoru; Kitagawa, Masahiro

2005-07-01

To evaluate the effects of supplementing diets with carotenoid and ascorbic acid (AsA) on the antioxidative ability of Osteogenic Disorder-Shionogi (ODS) rats, we added synthetic beta-carotene (betaC), AsA, and powders of persimmon (Ka) and pods (Po) containing betaC and AsA to the diet and obtained the following results. The urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was low in the -betaC.AsA and +AsA groups but high in the +betaC.AsA, +Ka, and +Po groups. The thiobarbituric acid-reactive substances (TBARS) in both the liver and skin were higher in the -betaC.AsA group than in the +betaC.AsA group and were low in the +Ka and +Po groups. As antioxidant enzymes, glutathione peroxidase (GSH-Px) activity was high in the +betaC.AsA group, low in the -beta3C.AsA group in both the skin and liver, and also high in the + Ka and +Po group in the liver. Superoxide dismutase (SOD) activity was high in the -betaC.AsA group and low in the +betaC.AsA and +Ka groups in both the skin and liver. Catalase (CAT) activity in the liver was low in the -betaC.AsA, +AsA, and +betaC groups and high in the +betaC.AsA and +Po groups. These results confirmed that the administration of betaC, AsA, and persimmons and pods increases antioxidative ability in the skin and liver of ultraviolet-b(UV-B)-irradiated ODS rats.

Clinical Effects of Formulated Food of Peucedanum japonicum Extract and Saw Palmetto Extract in Male Patients with Lower Urinary Tract Symptoms.

PubMed

Kageyama, Shinji; Beppu, Masanori; Ohnogi, Hiromu; Miyazaki, Sayaka; Haruno, Akihiro; Ito, Yoshihiko; Yamada, Shizuo

2018-05-01

To evaluate changes over time in subjective symptom scores and urination parameters before and after oral administration of formulated food containing a combination of Peucedanum japonicum (P. japonicum) extract and saw palmetto extract (SPE) in male patients with lower urinary tract symptoms (LUTS). This study was conducted in an open label manner on male patients with untreated LUTS. The urination state of patients was evaluated before and after administration of food formulated with P. japonicum extract and SPE for 4 weeks, based on urodynamic parameters and subjective symptom scores (International Prostate Symptom Score [IPSS and IPSS-QOL], Overactive Bladder Symptom Score [OABSS], Overactive Bladder Questionnaire [OAB-q], and International Index of Erectile Function [IIEF]). After the administration of food formulated with these extracts, the following results were obtained: (i) Subjective findings: The IPSS-QOL score improved significantly; both parameters related to nocturia, i.e., frequency of nighttime urination and OABSS-2, improved significantly; other ratings for subjective symptoms slightly improved. (ii) Objective findings: Residual urine volume decreased significantly, and blood prostate specific antigen (PSA) and urinary 8-OHdG levels decreased slightly after the treatment. (iii) Other findings: Blood pressure decreased slightly. No adverse drug reactions were reported. (iv) Patient impressions: 75% of patients gave a rating of "Good" or higher, with 15 out of 20 patients wanting to continue treatment after the end of 4-week administration period. Food formulated with P. japonicum extract and SPE may be useful to decrease frequency of nighttime urination and residual urine volume in male patients with LUTS. © 2017 John Wiley & Sons Australia, Ltd.

Predictors and Variability of Urinary Paraben Concentrations in Men and Women, Including before and during Pregnancy

PubMed Central

Smith, Kristen W.; Braun, Joe M.; Williams, Paige L.; Ehrlich, Shelley; Correia, Katharine F.; Calafat, Antonia M.; Ye, Xiaoyun; Ford, Jennifer; Keller, Myra; Meeker, John D.

2012-01-01

Background: Parabens are suspected endocrine disruptors and ubiquitous preservatives used in personal care products, pharmaceuticals, and foods. No studies have assessed the variability of parabens in women, including during pregnancy. Objective: We evaluated predictors and variability of urinary paraben concentrations. Methods: We measured urinary concentrations of methyl (MP), propyl (PP), and butyl paraben (BP) among couples from a fertility center. Mixed-effects regression models were fit to examine demographic predictors of paraben concentrations and to calculate intraclass correlation coefficients (ICCs). Results: Between 2005 and 2010, we collected 2,721 spot urine samples from 245 men and 408 women. The median concentrations were 112 µg/L (MP), 24.2 µg/L (PP), and 0.70 µg/L (BP). Urinary MP and PP concentrations were 4.6 and 7.8 times higher in women than men, respectively, and concentrations of both MP and PP were 3.8 times higher in African Americans than Caucasians. MP and PP concentrations we CI re slightly more variable in women (ICC = 0.42, 0.43) than men (ICC = 0.54, 0.51), and were weakly correlated between partners (r = 0.27–0.32). Among 129 pregnant women, urinary paraben concentrations were 25–45% lower during pregnancy than before pregnancy, and MP and PP concentrations were more variable (ICCs of 0.38 and 0.36 compared with 0.46 and 0.44, respectively). Conclusions: Urinary paraben concentrations were more variable in women compared with men, and during pregnancy compared with before pregnancy. However, results for this study population suggest that a single urine sample may reasonably represent an individual’s exposure over several months, and that a single sample collected during pregnancy may reasonably classify gestational exposure. PMID:22721761

Predictors and variability of urinary paraben concentrations in men and women, including before and during pregnancy.

PubMed

Smith, Kristen W; Braun, Joe M; Williams, Paige L; Ehrlich, Shelley; Correia, Katharine F; Calafat, Antonia M; Ye, Xiaoyun; Ford, Jennifer; Keller, Myra; Meeker, John D; Hauser, Russ

2012-11-01

Parabens are suspected endocrine disruptors and ubiquitous preservatives used in personal care products, pharmaceuticals, and foods. No studies have assessed the variability of parabens in women, including during pregnancy. We evaluated predictors and variability of urinary paraben concentrations. We measured urinary concentrations of methyl (MP), propyl (PP), and butyl paraben (BP) among couples from a fertility center. Mixed-effects regression models were fit to examine demographic predictors of paraben concentrations and to calculate intraclass correlation coefficients (ICCs). Between 2005 and 2010, we collected 2,721 spot urine samples from 245 men and 408 women. The median concentrations were 112 µg/L (MP), 24.2 µg/L (PP), and 0.70 µg/L (BP). Urinary MP and PP concentrations were 4.6 and 7.8 times higher in women than men, respectively, and concentrations of both MP and PP were 3.8 times higher in African Americans than Caucasians. MP and PP concentrations were slightly more variable in women (ICC = 0.42, 0.43) than men (ICC = 0.54, 0.51), and were weakly correlated between partners (r = 0.27-0.32). Among 129 pregnant women, urinary paraben concentrations were 25-45% lower during pregnancy than before pregnancy, and MP and PP concentrations were more variable (ICCs of 0.38 and 0.36 compared with 0.46 and 0.44, respectively). Urinary paraben concentrations were more variable in women compared with men, and during pregnancy compared with before pregnancy. However, results for this study population suggest that a single urine sample may reasonably represent an individual's exposure over several months, and that a single sample collected during pregnancy may reasonably classify gestational exposure.

Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

PubMed

Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

2015-12-01

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Oxidative Stress and Genotoxicity of Long-Term Occupational Exposure to Low Levels of BTEX in Gas Station Workers

PubMed Central

Xiong, Feng; Li, Qin; Zhou, Bo; Huang, Jiongli; Liang, Guiqiang; Zhang, Li’e; Ma, Shuyan; Qing, Li; Liang, Linhan; Su, Jing; Peng, Xiaowu; Li, Qin; Zou, Yunfeng

2016-01-01

Atmospheric benzene, toluene, ethylbenzene, and xylenes (BTEX) can lead to multiple health injuries. However, what remains uncertain is the effect of long-term exposure to low levels of BTEX. Thus, we determined the BTEX levels in the air from the refueling and office areas in gas stations. Then we collected workers’ (200 refueling vs. 52 office workers) peripheral blood samples to analyze the serum total-superoxide dismutase (T-SOD), glutathione (GSH), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) levels. DNA damage was analyzed by the comet assay and micronucleus test in buccal epithelial cells. We found that the levels of BTEX in refueling areas were significantly higher than those in office areas (p < 0.001). The serum T-SOD and GSH of refueling workers were significantly lower than those in office workers (p < 0.001). By contrast, the serum MDA and 8-OHdG of refueling workers were significantly higher than those of office workers (p < 0.001, MDA; p = 0.025, 8-OHdG). Furthermore, tail and Olive tail moments in refueling workers were longer (p = 0.004, tail moment; p = 0.001, Olive tail moment), and the micronucleus rate was higher (p < 0.001) than those in office workers. Taken together, long-term exposure to low levels of BTEX may reduce the antioxidant ability and increase the risk of DNA damage in refueling workers of gas stations. PMID:27929445

Early-life exposure to air pollutants and adverse pregnancy outcomes: protocol for a prospective cohort study in Beijing.

PubMed

Song, Jing; Chen, Yi; Wei, Ling; Ma, Ying; Tian, Ning; Huang, Shi Yun; Dai, Yin Mei; Zhao, Li Hong; Kong, Yuan Yuan

2017-09-03

The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. Here , 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. This study has been registered in WHO International Clinical Trial Register-Chinese Clinical Trial Registry under registrationnumber ChiCTR-ROC-16010181 (http :// www.chictr.org.cn / showproj.aspx ?proj=17328). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Increased levels of mitochondrial DNA copy number in patients with vitiligo.

PubMed

Vaseghi, H; Houshmand, M; Jadali, Z

2017-10-01

Oxidative stress is known to be involved in the pathogenesis of autoimmune diseases such as vitiligo. Evidence suggests that the human mitochondrial DNA copy number (mtDNAcn) is vulnerable to damage mediated by oxidative stress. The purpose of this study was to examine and compare peripheral blood mtDNAcn and oxidative DNA damage byproducts (8-hydroxy-2-deoxyguanosine; 8-OHdG) in patients with vitiligo and healthy controls (HCs). The relative mtDNAcn and the oxidative damage (formation of 8-OHdG in mtDNA) of each sample were determined by real-time quantitative PCR. Blood samples were obtained from 56 patients with vitiligo and 46 HCs. The mean mtDNAcn and the degree of mtDNA damage were higher in patients with vitiligo than in HCs. These data suggest that increase in mtDNAcn and oxidative DNA damage may be involved in the pathogenesis of vitiligo. © 2017 British Association of Dermatologists.

Early life low-level cadmium exposure is positively associated with increased oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kippler, Maria; Bakhtiar Hossain, Mohammad; Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund

Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodGmore » was 3.9 nmol/L, urinary Cd 0.30 {mu}g/L, and breast-milk Cd 0.13 {mu}g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.« less

Urinary and plasma oxalate during ingestion of pure ascorbic acid: a re-evaluation.

PubMed

Fituri, N; Allawi, N; Bentley, M; Costello, J

1983-01-01

Daily ingestion of 8 g of pure ascorbic acid by 8 normal subjects for 7 days did not, in contrast to previous reports in the literature, significantly alter urinary or plasma oxalate during or after ingestion. When urine with raised ascorbate values was heated at 100 degrees C for 30 min, a significant increase in urinary oxalate concentration was observed. Plasma ascorbate reached a mean value during ingestion of 3.3 mg/100 ml. Urinary citrate excretion significantly decreased during the first 4 days of ascorbic acid ingestion; however, the urinary inhibitory activity of calcium oxalate crystal growth was not significantly altered. Urinary and serum urate as well as urinary calcium and magnesium were unaltered by ingestion of the vitamin supplement.

Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed drinking water

PubMed Central

2014-01-01

Background Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose–response relationship in the application of hydrogen is puzzling. We attempted to identify the dose–response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. Methods In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. Results Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. Conclusions Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose–response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress. PMID:24589018

Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed drinking water.

PubMed

Xue, Jinling; Shang, Guodong; Tanaka, Yoshinori; Saihara, Yasuhiro; Hou, Lingyan; Velasquez, Natalia; Liu, Wenjun; Lu, Yun

2014-03-03

Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose-response relationship in the application of hydrogen is puzzling. We attempted to identify the dose-response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose-response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress.

Hydrogen peroxide-induced DNA damage is independent of nuclear calcium but dependent on redox-active ions.

PubMed Central

Jornot, L; Petersen, H; Junod, A F

1998-01-01

In cells undergoing oxidative stress, DNA damage may result from attack by .OH radicals produced by the Fenton reaction, and/or by nucleases activated by nuclear calcium. In the present study, the participation of these two mechanisms was investigated in HeLa cells. Nuclear-targeted aequorin was used for selectively monitoring Ca2+ concentrations within the nuclei ([Ca2+]n), in conjunction with the cell-permeant calcium chelator bis-(o-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), the lipid-soluble broad-spectrum metal chelator with low affinity for Ca2+ and Mg2+ N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), and the high-affinity iron/copper chelator 1, 10-phenanthroline (PHE). In Ca2+-containing medium, H2O2 induced extensive DNA strand breaks and an increase in [Ca2+]n that was almost identical to that observed in the cytosol ([Ca2+]c). In cells bathed in Ca2+-free/EGTA medium, in which the increases in [Ca2+]n and [Ca2+]c due to H2O2 were significantly reduced, similar levels of DNA fragmentation also occurred. In cells preloaded with BAPTA/AM or TPEN, the small increase of [Ca2+]n normally elicited by H2O2 in Ca2+-free medium was completely buffered, and DNA damage was largely prevented. On the other hand, pretreatment with PHE did not affect the calcium response in the nuclei, but completely prevented DNA strand breakage induced by H2O2. Re-addition of 100 microM CuSO4 and 100 microM FeSO4 to TPEN- and PHE-treated cells prior to H2O2 challenge reversed the effect of TPEN and PHE, whereas 1 mM was necessary to negate the effect of BAPTA/AM. The levels of DNA strand breakage observed, however, did not correlate with the amounts of 8-hydroxy 2'-deoxyguanosine (8-OHdG): H2O2 did not produce 8-OHdG, whereas PHE alone slightly increased 8-OHdG levels. CuSO4 and FeSO4 enhanced the effects of PHE, particularly in the presence of H2O2. Exposure of cells to a mixture of CuSO4/FeSO4 also resulted in a significant increase in 8-OHdG levels, which was prevented in cells preloaded with BAPTA/AM. Similar results were obtained in a cell-free system using isolated calf thymus DNA exposed to CuSO4/FeSO4, regardless of whether H2O2 was present or not. These results suggest that BAPTA/AM prevents H2O2-induced DNA damage by acting as an iron/copper chelator. These data also indicate that caution must be exercised in using Ca2+ chelating agents as evidence for a role in cellular Ca2+ levels in experimental conditions in which transition-metal-ion-mediated oxidant production is also occurring. PMID:9742216

Urinary Polycyclic Aromatic Hydrocarbon (OH-PAH) Metabolite Concentrations and the Effect of GST Polymorphisms Among US Air Force Personnel Exposed to Jet Fuel

PubMed Central

Rodrigues, Ema G.; Smith, Kristen; Maule, Alexis L.; Sjodin, Andreas; Li, Zheng; Romanoff, Lovisa; Kelsey, Karl; Proctor, Susan; McClean, Michael D.

2016-01-01

Objective To evaluate the association between inhalation exposure to jet propulsion fuel 8 (JP-8) and urinary metabolites among US Air Force (USAF) personnel, and investigate the role of glutathione S-transferase polymorphisms. Methods Personal air samples were collected from 37 full-time USAF personnel during 4 consecutive workdays and analyzed for JP-8 constituents and total hydrocarbons. Pre- and postshift urine samples were collected each day and analyzed for polycyclic aromatic hydrocarbon urinary metabolites. Results Work shift exposure to total hydrocarbons was significantly associated with postshift urinary 1-naphthol (β = 0.17; P = <0.0001), 2-naphthol (β = 0.09; P = 0.005), and 2-hydroxyfluorene concentrations (β = 0.08; P = 0.006), and a significant gene-environment interaction was observed with glutathione S-transferase mu-1. Conclusions USAF personnel experience inhalation exposure to JP-8, which is associated with absorption of JP-8 constituents while performing typical job-related tasks, and in our data the glutathione S-transferase mu-1 polymorphism was associated with differential metabolism of naphthalene. PMID:24806557

Urinary polycyclic aromatic hydrocarbon (OH-PAH) metabolite concentrations and the effect of GST polymorphisms among US Air Force personnel exposed to jet fuel.

PubMed

Rodrigues, Ema G; Smith, Kristen; Maule, Alexis L; Sjodin, Andreas; Li, Zheng; Romanoff, Lovisa; Kelsey, Karl; Proctor, Susan; McClean, Michael D

2014-05-01

To evaluate the association between inhalation exposure to jet propulsion fuel 8 (JP-8) and urinary metabolites among US Air Force (USAF) personnel, and investigate the role of glutathione S-transferase polymorphisms. Personal air samples were collected from 37 full-time USAF personnel during 4 consecutive workdays and analyzed for JP-8 constituents and total hydrocarbons. Pre- and postshift urine samples were collected each day and analyzed for polycyclic aromatic hydrocarbon urinary metabolites. Work shift exposure to total hydrocarbons was significantly associated with postshift urinary 1-naphthol (β = 0.17; P = <0.0001), 2-naphthol (β = 0.09; P = 0.005), and 2-hydroxyfluorene concentrations (β = 0.08; P = 0.006), and a significant gene-environment interaction was observed with glutathione S-transferase mu-1. USAF personnel experience inhalation exposure to JP-8, which is associated with absorption of JP-8 constituents while performing typical job-related tasks, and in our data the glutathione S-transferase mu-1 polymorphism was associated with differential metabolism of naphthalene.

Oxidative stress markers are associated to vascular recurrence in non-cardioembolic stroke patients non-treated with statins

PubMed Central

2012-01-01

Background Since atherogenesis is related to oxidative stress, our objective was to study the association of oxidative stress markers with the vascular recurrence in non-cardioembolic stroke. Methods Atherosclerotic and oxidative stress markers were evaluated on admission, in 477 patients suffering from a first non-cardioembolic stroke. Patients were followed at 6 and 12 months after inclusion, recording cardiovascular events. As markers of endothelial oxidative stress we used oxidized LDL, Cu/Zn superoxide dismutase and 8-OH deoxiguanosine. 136 patients were being treated with statins at the moment of serum samples acquisition. Results Patients who suffered vascular recurrence or vascular-origin death had higher levels of 8-OHDG (40.06±24.70vs33.11±15.18;p=0.003). We also found associations between vascular recurrence or vascular origin death and Cu/ZnSOD (OR,1.02; 95%CI,1.00-1.03;p=0.0001) and 8-OHDG (OR,1.12;95%CI,1.08-1.16;p<0.0001) in a subgroup of 333 patients that were not in treatment with statins on admission. We also found associations between 8-OHDG and intima media thickness (IMT) (OR,1.13;95%CI,1.09-1.16;p<0.0001), presence of ipsilatieral stenosis≥50% (OR,1.03;95%CI1.00-1.05;p=0.007) and other atherosclerotic plaque characteristics. Conclusions Specific oxidative stress markers were found to be markers of atherosclerosis plaque types and vascular recurrence in non-statins treated patients at admission. PMID:22862793

Screening and Characterization of Drugs That Protect Corneal Endothelial Cells Against Unfolded Protein Response and Oxidative Stress

PubMed Central

Kim, Eun Chul; Toyono, Tetsuya; Berlinicke, Cynthia A.; Zack, Donald J.; Jurkunas, Ula; Usui, Tomohiko; Jun, Albert S.

2017-01-01

Purpose To screen for and characterize compounds that protect corneal endothelial cells against unfolded protein response (UPR) and oxidative stress. Methods Bovine corneal endothelial cells (BCECs) were treated for 48 hours with 640 compounds from a Food and Drug Administration (FDA)-approved drug library and then challenged with thapsigargin or H2O2 to induce UPR or oxidative stress, respectively. Cell viability was measured using the CellTiter-Glo survival assay. Selected “hits” were subjected to further dose-response testing, and their ability to modulate expression of UPR and oxidative stress markers was assessed by RT-PCR, Western blot, and measurement of protein carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) adducts in immortalized human corneal endothelial cells (iHCECs). Results Forty-one drugs at 20 μM and 55 drugs at 100 μM increased survival of H2O2-challenged cells, and 8 drugs at 20 μM and 2 drugs at 100 μM increased survival of thapsigargin-challenged cells, compared with untreated control cells. Nicergoline, ergothioneine, nimesulide, oxotremorine, and mefenamic acid increased survival of both H2O2- and thapsigargin-challenged cells. Oxotremorine altered DNA damage inducible 3 (CHOP) gene expression, glucose-regulated protein 78 kDa (GRP78) and activating transcription factor 4 (ATF4) protein expression, and protein carbonyl and 8-OHdG levels. Mefenamic acid altered GRP78 protein expression and protein carbonyl and 8-OHdG levels. Conclusions Oxotremorine and mefenamic acid are potential survival factors for corneal endothelial cells under UPR and oxidative stress. The described assay can be further expanded to screen additional drugs for potential therapeutic effect in corneal endothelial diseases such as Fuchs' endothelial corneal dystrophy. PMID:28159976

Screening and Characterization of Drugs That Protect Corneal Endothelial Cells Against Unfolded Protein Response and Oxidative Stress.

PubMed

Kim, Eun Chul; Toyono, Tetsuya; Berlinicke, Cynthia A; Zack, Donald J; Jurkunas, Ula; Usui, Tomohiko; Jun, Albert S

2017-02-01

To screen for and characterize compounds that protect corneal endothelial cells against unfolded protein response (UPR) and oxidative stress. Bovine corneal endothelial cells (BCECs) were treated for 48 hours with 640 compounds from a Food and Drug Administration (FDA)-approved drug library and then challenged with thapsigargin or H2O2 to induce UPR or oxidative stress, respectively. Cell viability was measured using the CellTiter-Glo survival assay. Selected "hits" were subjected to further dose-response testing, and their ability to modulate expression of UPR and oxidative stress markers was assessed by RT-PCR, Western blot, and measurement of protein carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) adducts in immortalized human corneal endothelial cells (iHCECs). Forty-one drugs at 20 μM and 55 drugs at 100 μM increased survival of H2O2-challenged cells, and 8 drugs at 20 μM and 2 drugs at 100 μM increased survival of thapsigargin-challenged cells, compared with untreated control cells. Nicergoline, ergothioneine, nimesulide, oxotremorine, and mefenamic acid increased survival of both H2O2- and thapsigargin-challenged cells. Oxotremorine altered DNA damage inducible 3 (CHOP) gene expression, glucose-regulated protein 78 kDa (GRP78) and activating transcription factor 4 (ATF4) protein expression, and protein carbonyl and 8-OHdG levels. Mefenamic acid altered GRP78 protein expression and protein carbonyl and 8-OHdG levels. Oxotremorine and mefenamic acid are potential survival factors for corneal endothelial cells under UPR and oxidative stress. The described assay can be further expanded to screen additional drugs for potential therapeutic effect in corneal endothelial diseases such as Fuchs' endothelial corneal dystrophy.

Ebselen attenuates oxidative DNA damage and enhances its repair activity in the thalamus after focal cortical infarction in hypertensive rats.

PubMed

He, Meixia; Xing, Shihui; Yang, Bo; Zhao, Liqun; Hua, Haiying; Liang, Zhijian; Zhou, Wenliang; Zeng, Jinsheng; Pei, Zhong

2007-11-21

Oxidative DNA damage has been proposed to be a major contributor to focal cerebral ischemic injury. However, little is known about the role of oxidative DNA damage in remote damage secondary to the primary infarction. In the present study, we investigated oxidative damage within the ventroposterior nucleus (VPN) after distal middle cerebral artery occlusion (MCAO) in hypertensive rats. We also examined the possible protective effect of ebselen, one glutathione peroxidase mimic, on delayed degeneration in the VPN after distal MCAO. Neuronal damage in the ipsilateral VPN was examined by Nissl staining. Oxidative DNA damage and base repair enzyme activity were assessed by analyzing immunoreactivity of 8-hydroxy-2'-deoxyguanosine (8-ohdG) and 8-oxoguanine DNA glycosylase (OGG1), respectively. The number of intact neurons in the ipsilateral VPN decreased by 52% compared to the contralateral side in ischemia group 2 weeks after distal cerebral cortical infarction. The immunoreactivity of 8-ohdG significantly increased while OGG1 immunoreactivity significantly decreased in the ipsilateral VPN 2 weeks after distal cortical infarction (all p<0.01). Compared with vehicle treatment, ebselen significantly attenuated the neuron loss, ameliorated ischemia-induced increase in 8-ohdG level as well as decrease in OGG1 level within the ipsilateral VPN (all p<0.01). OGG1 was further demonstrated to mainly express in neurons. These findings strongly suggest that oxidative DNA damage may be involved in the delayed neuronal death in the VPN region following distal MCAO. Furthermore, ebselen protects against the delayed damage in the VPN when given at 24 h following distal MCAO.

Urinary metabolite levels and symptoms in Filipino workers using organic solvents.

PubMed

Cucueco, M T; Espinosa, N C; Villanueva, M B; Castro, F T; Sison, S Y; Ortega, V S; Hisanaga, N

1993-01-01

To compare symptoms with urinary metabolite levels, 900 workers from 7 organic solvent-using industries were studied. Urinary metabolites were determined using a high performance liquid chromatograph. Urinary hippuric acid concentrations exceeding the reference value (2.5 g/g creatinine) were found in 78 (8.7%) workers. However, only 3 (0.3%) and 1 (0.1%) of the participants exceeded the reference value for mandelic (0.8 g/g creatinine) and total methylhippuric acid (1.5 g/g creatinine), respectively. The sum of the values of the ratio of measured urinary metabolite concentration to the corresponding ACGIH's biological exposure indices (BEI) [(HA/BEI of HA + MHA/BEI of MHA + MA/BEI of MA)] exceeded 1.0 in 166 (18.4%) workers. Majority of them were from the footwear manufacturing industry (63/129 or 49.2%). Questionnaire interviews were also administered to determine the prevalence of symptoms while at work (acute symptoms) or within the past 6 months (chronic symptoms). Urinary metabolite levels of individual and mixed solvents were compared with the symptoms of all workers. Analysis using Spearman's rank correlation showed in workers whose urinary hippuric acid exceeded 3.75 g/g creatine (1.5 x BEI), significant correlation between their hippuric acid levels and subjective complaints. Workers whose sum of the values of the ratio of measured urinary metabolite concentration to corresponding BEI exceeded 1.5 were selected and comparing this level with their symptoms, significant correlation was also noted in some complaints.

Plasma Pentosidine and Its Association with Mortality in Patients with Chronic Kidney Disease

PubMed Central

Sun, Jia; Qureshi, Abdul Rashid; Isoyama, Naohito; Leurs, Paul; Anderstam, Björn; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Lindholm, Bengt

2016-01-01

Background Circulating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD). Here we evaluated factors linked to increased plasma pentosidine and its association with mortality in patients with different stages of CKD and undergoing different treatments. Methods Plasma pentosidine, biomarkers of inflammation, oxidative stress and nutritional status were investigated in CKD 1–2 (n = 37), CKD 3–4 (n = 54), CKD 5 non-dialyzed (CKD5-ND; n = 386), peritoneal dialysis (PD; n = 74) and hemodialysis (HD; n = 195) patients. Factors predicting plasma pentosidine were analysed by multivariate regression analysis and mortality risk was assessed by GENMOD procedure. Results Plasma pentosidine levels, which were higher in CKD5-ND, PD and HD groups than in CKD 1–2 group, were significantly lower in PD than in HD patients, and not different between PD patients and CKD5-ND patients. Pentosidine associated inversely with glomerular filtration rate (GFR), and additionally in PD with 8-hydroxy-2‘-deoxyguanosine (8-OHdG), and interleukin 6 (IL-6); in HD with age, IL-6 and body mass index (BMI); in CKD5-ND with age, 8-OHdG, IL-6, high-sensitive C-reactive protein (hsCRP), and soluble vascular cell adhesion protein-1 (sVCAM-1); in CKD 3–4 with 8-OHdG and sVCAM-1; and in CKD 1–2 with age and sVCAM-1. In multivariate analysis, age (one standard deviation, 1-SD higher), malnutrition (subjective global assessment, SGA), oxidative stress (8-OHdG, 1-SD higher), and belonging to CKD5-ND, HD and PD cohorts associated with 1-SD higher pentosidine. In GENMOD, 1-SD higher pentosidine independently predicted all-cause mortality (relative risk, RR = 1.04; 95% confidence interval, CI, 1.01–1.08, p = 0.01) and CVD mortality (RR = 1.03; 95% CI, 1.01–1.06, p = 0.03) after adjusting for all confounders. Conclusions Plasma pentosidine is markedly elevated in CKD and associates with low GFR, oxidative stress and inflammation, and is an independent predictor of mortality in CKD patients. PMID:27701453

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

PubMed

Araki, S; Aono, H; Murata, K

1986-09-01

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings.

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

PubMed Central

Araki, S; Aono, H; Murata, K

1986-01-01

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings. PMID:3092853

Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats.

PubMed

Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko; Murat, Dogru; Nakamura, Shigeru; Nakashima, Hideo; Shimmura, Shigeto; Shinmura, Ken; Tsubota, Kazuo

2010-07-09

A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome. Copyright 2010 Elsevier Inc. All rights reserved.

Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats.

PubMed

Kim, Kyoung-Ok; Park, HyunJin; Chun, Mison; Kim, Hyun-Sook

2014-09-01

We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.

Female Reproductive Hormones and Biomarkers of Oxidative Stress in Genital Chlamydia Infection in Tubal Factor Infertility

PubMed Central

Nsonwu-Anyanwu, Augusta Chinyere; Charles-Davies, Mabel Ayebantoyo; Taiwo, Victor Olusegun; Li, Bin; Oni, Anthony Alabar; Bello, Folashade Adenike

2015-01-01

Background Genital Chlamydia infection (GCI) and the associated pathologies have been implicated in tubal infertility. Though the actual pathologic mechanisms are still uncertain, oxidative stress and other factors have been implicated. The purpose of the study was to determine the possible contribution of female reproductive hormones and biomarkers of oxidative stress in genital Chlamydial infection to tubal occlusion. Methods This prospective case control study was carried out by recruiting 150 age matched women grouped into infertile Chlamydia positive women (n = 50), fertile Chlamydia positive women (n = 50) and fertile Chlamydia negative women as controls (n = 50). High vaginal swabs and endocervical swabs were collected for screening Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, Staphylococcus aureus, and Candida albicans. Sera were collected for estimation of Chlamydia trachomatis antibody, female reproductive hormones [Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Oestradiol (E2), Progesterone (P4), Prolactin (PRL)] and biomarkers of oxidative stress [Total Antioxidant Capacity (TAC) and 8-hydroxyl-2-deoxyguanosine (8-OHdG)] by enzyme immunoassay (EIA). Data were analyzed using chi square, analysis of variance and LSD Post hoc to determine mean differences at p = 0.05. Results Among women with GCI, higher levels of LH and 8-OHdG were observed in infertile Chlamydia positive women compared to fertile Chlamydia positive women (p < 0.05). Higher levels of LH and 8-OHdG and lower TAC levels were observed in infertile Chlamydia positive women compared to fertile Chlamydia negative controls (p < 0.05). Conclusion Mechanisms including oxidative DNA damage and reduced antioxidant capacity may be involved in the pathology of Chlamydia induced tubal damage. PMID:25927024

Urinary thiocyanate concentrations are associated with adult cancer and lung problems: US NHANES, 2009-2012.

PubMed

Shiue, Ivy

2015-04-01

Links between environmental chemicals and human health have emerged but the effects from perchlorate, nitrate and thiocyanate were unclear. Therefore, it was aimed to study the relationships of urinary perchlorate, nitrate and thiocyanate concentrations and adult health conditions in a national and population-based study. Data was retrieved from US National Health and Nutrition Examination Surveys, 2009-2012, including demographics, blood pressure readings, self-reported health conditions and urinary perchlorate, nitrate and thiocyanate concentrations. Analyses included chi-square test, t test survey-weighted logistic regression models and population attributable risk estimation. There were no clear associations between urinary perchlorate concentrations and adult health conditions, although people with hearing loss and diabetes could be at the borderline risk. Urinary thiocyanate concentrations were significantly associated with emphysema (odds ratio (OR) 2.70 95% confidence intervals (CI) 1.91-3.82, P < 0.001), cancer (OR 1.21 95%CI 1.06-1.39, P = 0.008), chronic bronchitis (OR 1.23 95%CI 1.10-1.52, P = 0.003), wheezing (OR 1.24 95%CI 1.05-1.46, P = 0.011), coughing (OR 1.19 95%CI 1.03-1.37, P = 0.018) and sleep complaints (OR 1.14 95%CI 1.02-1.26, P = 0.019). The population attributable risks accounted for 3.3% (1.8-5.3%), 1.9% (0.6-3.5%), 1.2% (0.5-2.6%), 2.2% (0.5-4.1%), 1.8% (0.3-6.2%) and 1.3% (0.2-2.4%) for emphysema, cancer, chronic bronchitis, wheezing, coughing and sleep complaints, respectively. In addition, there was an inverse association observed between urinary nitrate level and heart failure. This is for the first time observing significant risk effects of urinary thiocyanate concentrations on adult cancer and lung problems, although the causality cannot be established. Elimination of such environmental chemical in humans should be included in future health policy and intervention programs.

Relationship between oxidative damage and colon carcinogenesis in irradiated rats: influence of dietary countermeasures

NASA Astrophysics Data System (ADS)

Turner, Nancy; Sanders, Lisa; Wu, Guoyao; Davidson, Laurie; Ford, John; Braby, Leslie; Carroll, Raymond; Chapkin, Robert; Lupton, Joanne

Galactic cosmic radiation not only kills colon epithelial cells, it also generates a cellular environment that can lead to oxidative DNA damage. We previously demonstrated that a diet containing fish oil and pectin protects against initiation of colon cancer by enhancing apoptotic removal of cells with oxidative DNA adducts (8-OHdG), and that apoptosis was highly correlated with colon cancer suppression. We hypothesized this diet combination will mitigate the oxidative damage occurring from radiation and thus reduce colon cancer. The experiment tested the effect of radiation (± 1 Gy, 1 GeV/n Fe ions) on redox balance, apoptosis, and 8-OHdG levels at initiation and colon tumor incidence. Diets contained fish oil or corn oil, and cellulose or pectin (2x2 factorial design). Rats received the diets 3 wk before irradiation (half of the rats), followed by azoxymethane (AOM) injections 10 and 17 d later (all rats). Just prior to AOM injection, irradiated fish oil/pectin rats had a more reduced redox state in colonocytes (lower GSSG, P < 0.05; higher GSH/GSSG ratio), which was not observed in irradiated corn oil/cellulose rats. A shift to a more oxidative state (lower GSH and GSH/GSSG ratio, P < 0.05) occurred between 6 and 12 h after AOM in the fish oil/pectin irradiated rats. Changes in redox balance likely contributed to lower 8-OHdG levels in colonocytes from rats consuming the fish oil diets. Dietary pectin enhanced (P < 0.04) apoptosis induction 12 h after AOM injection in irradiated rats. Similar to the 8-OHdG results, colon tumor incidence was 42% higher (P < 0.05) in rats fed corn oil vs fish oil diets. In summary, fish oil/pectin diets created a more reduced colon environment in irradiated rats that was evident 10 d after irradiation. The ensuing oxidative shift in those rats after AOM injection may have enhanced apoptosis; effectively eliminating more DNA damaged cells. Thus, inclusion of fish oil and pectin in diets for long-duration space flights should help suppress the elevation in colon cancer risk caused by galactic cosmic radiation. Funded by NSBRI (NASA NCC 9-58), NIH CA90301, NIEHS P-30-ES09106.

Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mínguez-Alarcón, Lidia, E-mail: lminguez@hsph.harv

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer, was introduced commercially in 2002 as an alternative to ortho-phthalate esters because of its favorable toxicological profile. However, the potential health effects from DINCH exposure remain largely unknown. We explored the associations between urinary concentrations of metabolites of DINCH on markers of ovarian response among women undergoing in vitro fertilization (IVF) treatments. Between 2011 and 2015, 113 women enrolled a prospective cohort study at the Massachusetts General Hospital Fertility Center and provided up to two urine samples prior to oocyte retrieval. The urinary concentrations of two DINCH metabolites, cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH) andmore » cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), were quantified by isotope dilution tandem mass spectrometry. We used generalized linear mixed models to evaluate the association between urinary metabolite concentrations and markers of ovarian response, accounting for multiple IVF cycles per woman via random intercepts. On average, women with detectable urinary MHiNCH concentrations, as compared to those below LOD, had a lower estradiol levels (−325 pmol/l, p=0.09) and number of retrieved oocytes (−1.8, p=0.08), with a stronger association among older women. However, urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness. In conclusion, we found suggestive negative associations between urinary MHiNCH concentrations and peak estradiol levels and number of total oocyte yields. This is the first study evaluating the effect of DINCH exposure on human reproductive health and raises the need for further experimental and epidemiological studies to better understand the potential effects of this chemical on health. - Highlights: • Women with detectable urinary MHiNCH concentrations had a lower estradiol levels and number of retrieved oocytes. • The negative association between urinary MHiNCH concentrations and total oocyte yield was stronger in older women. • Urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness.« less

An experimental double-blind irradiation study of a novel topical product (TPF 50) compared to other topical products with DNA repair enzymes, antioxidants, and growth factors with sunscreens: implications for preventing skin aging and cancer.

PubMed

Emanuele, Enzo; Spencer, James M; Braun, Martin

2014-03-01

The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.

Increased methylation of repetitive elements and DNA repair genes is associated with higher DNA oxidation in children in an urbanized, industrial environment.

PubMed

Alvarado-Cruz, Isabel; Sánchez-Guerra, Marco; Hernández-Cadena, Leticia; De Vizcaya-Ruiz, Andrea; Mugica, Violeta; Pelallo-Martínez, Nadia Azenet; Solís-Heredia, María de Jesús; Byun, Hyang-Min; Baccarelli, Andrea; Quintanilla-Vega, Betzabet

2017-01-01

DNA methylation in DNA repair genes participates in the DNA damage regulation. Particulate matter (PM), which has metals and polycyclic aromatic hydrocarbons (PAHs) adsorbed, among others has been linked to adverse health outcomes and may modify DNA methylation. To evaluate PM exposure impact on repetitive elements and gene-specific DNA methylation and DNA damage, we conducted a cross-sectional study in 150 schoolchildren (7-10 years old) from an urbanized, industrial area of the metropolitan area of Mexico City (MAMC), which frequently exhibits PM concentrations above safety standards. Methylation (5mC) of long interspersed nuclear element-1 (LINE1) and DNA repair gene (OGG1, APEX, and PARP1) was assessed by pyrosequencing in peripheral mononuclear cells, DNA damage by comet assay and DNA oxidation by 8-OHdG content. PAH and metal contents in PM 10 (≤10μm aerodynamic diameter) were determined by HPLC-MS and ICP-AES, respectively. Multiple regression analysis between DNA methylation, DNA damage, and PM 10 exposure showed that PM 10 was significantly associated with oxidative DNA damage; a 1% increase in 5mC at all CpG sites in PARP1 promoter was associated with a 35% increase in 8-OHdG, while a 1% increase at 1, 2, and 3 CpG sites resulted in 38, 9, and 56% increments, respectively. An increase of 10pg/m 3 in benzo[b]fluoranthene content of PM 10 was associated with a 6% increase in LINE1 methylation. Acenaphthene, indene [1,2,3-cd] pyrene, and pyrene concentrations correlated with higher dinucleotide methylation in OGG1, APEX and PARP1 genes, respectively. Vanadium concentration correlated with increased methylation at selected APEX and PARP1 CpG sites. DNA repair gene methylation was significantly correlated with DNA damage and with specific PM 10 -associated PAHs and Vanadium. Data suggest that exposure to PM and its components are associated with differences in DNA methylation of repair genes in children, which may contribute to DNA damage. Copyright © 2016 Elsevier B.V. All rights reserved.

Monitoring of urinary calcium and phosphorus excretion in preterm infants: comparison of 2 methods.

PubMed

Staub, Eveline; Wiedmer, Nicolas; Staub, Lukas P; Nelle, Mathias; von Vigier, Rodo O

2014-04-01

Premature babies require supplementation with calcium (Ca) and phosphorus (P) to prevent metabolic bone disease of prematurity. To guide mineral supplementation, 2 methods of monitoring urinary excretion of Ca and P are used: urinary Ca or P concentration and Ca/creatinine (Crea) or P/Crea ratios. We compare these 2 methods in regards to their agreement on the need for mineral supplementation. Retrospective chart review of 230 premature babies with birth weight <1500 g, undergoing screening of urinary spot samples from day 21 of life and fortnightly thereafter. Hypothetical cutoff values for urine Ca or P concentration (1 mmol/L) and urine Ca/Crea ratio (0.5 mol/mol) or P/Crea ratio (4 mol/mol) were applied to the sample results. The agreement on whether to supplement the respective minerals based on the results with the 2 methods was compared. Multivariate general linear models sought to identify patient characteristics to predict discordant results. A total of 24.8% of cases did not agree on the indication for Ca supplementation, and 8.8% for P. Total daily Ca intake was the only patient characteristic associated with discordant results. With the intention to supplement the respective mineral, comparison of urinary mineral concentration with mineral/Crea ratio is moderate for Ca and good for P. The results do not allow identifying superiority of either method on the decision as to which babies require Ca and/or P supplements.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao, E-mail: xuwentaoboy@sina.com

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did notmore » affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in vitro.« less

DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: Involvement of the oxidative mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calviello, Gabriella; Piccioni, Elisabetta; Boninsegna, Alma

The DNA damaging and proapoptotic effects of Mancozeb, a widely used fungicide of the ethylene-bis-dithiocarbamate (EBDC) group, were studied in RAT-1 fibroblasts cultured in vitro and in peripheral blood mononucleated cells (PBMC) isolated from Wistar rats. After 1 h exposition to Mancozeb (up to 500 ng/ml), cells produced a dose-dependent induction in DNA single strand break (SSB) formation, measured by single cell gel electrophoresis (SCGE). Concomitantly, a concentration-dependent increase in the levels of the oxidative markers of DNA oxidation, the DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) and of reactive oxygen species (ROS) were observed, suggesting a prooxidant action of Mancozeb. PBMC weremore » less responsive than fibroblasts to the oxidative insult carried out by Mancozeb, as shown by the lower increase in the levels of ROS, 8-OHdG adducts and SSB measured in these cells after exposure to the pesticide. A 4-h treatment with Mancozeb induced also apoptosis in both PBMC and RAT-1 cells, even though leukocytes were less sensitive than fibroblasts to the proapoptotic action. This effect was dose-dependent and was inhibited by the action of the antioxidant {alpha}-tocopherol. The proapoptotic effect was accompanied by the altered expression of several proteins involved in the regulation of apoptosis, such as the prosurvival protein BCL-2 and the proapoptotic protein c-MYC. Exposition of cells to higher concentrations of Mancozeb or for longer periods (>4 h) caused post-apoptotic, necrotic alterations in cell membrane integrity. The data herein presented demonstrate the oxidative effect of Mancozeb and suggest that its prooxidant action may be involved in the proapoptotic effect exerted by this compound in rat cells. It appears possible that the observed oxidative and genotoxic damage may be involved in the pathogenesis of various pathologies associated with the chronic exposition to Mancozeb, including cancer. On the other hand, the proapoptotic effect of Mancozeb suggests its possible relevance in the pathogenesis of neurodegenerative diseases, often related to the exposition of pesticides.« less

Effectiveness of the iodine prophylaxis model adopted in Poland.

PubMed

Szybinski, Z; Golkowski, F; Buziak-Bereza, M; Trofimiuk, M; Przybylik-Mazurek, E; Huszno, B; Bandurska-Stankiewicz, E; Bar-Andziak, E; Dorant, B; Kinalska, I; Lewinski, A; Klencki, M; Rybakowa, M; Sowinski, J; Szewczyk, L; Szponar, L; Wasik, R

2008-04-01

Most of the Polish territory has been classified as an iodine-deficient and endemic goiter area according to the International Council for Control of Iodine Deficiency (ICCIDD) criteria. In 1997 the obligatory model of iodine prophylaxis was implemented. Our investigations were aimed at the effectiveness of iodine prophylaxis in Poland. We assessed urinary iodine excretion and goiter prevalence in 5663 children aged 6-12 yr. The population of children from the same 27 schools was investigated from 1992 to 1994 (1406 girls and 1244 boys) and from 1999 to 2005 (1563 girls and 1450 boys) using identical laboratory and ultrasound methods. We found significant increase in iodine urinary concentration (median 52 microg/l vs 93 microg/l, p<0.001) with accompanying drop in goiter prevalence (29.6% vs 5.2%, p<0.001) after implementation of iodine prophylaxis. Iodine excretion distribution changed significantly after 1997 with an increase in the percentage of children with iodine urinary concentration above 100 microg/l from 10.8% to 45.4%, respectively. A significantly higher iodine urinary concentration was observed in lowlands compared to uplands both before and after implementation of iodine prophylaxis (median, 50 microg/l vs 57 microg/l and 86 microg/l vs 114 microg/l, respectively, p<0.001). The goiter prevalence did not differ between girls and boys from 1992 to 1994 (28.8% vs 30.5%, p=0.35) and 1999 to 2005 (5.5% vs 4.9%, p=0.45). Implementation of the new model of iodine prophylaxis in Poland in 1997 has led to significant increase in iodine urinary concentration and decrease in goiter prevalence among Polish schoolchildren. In the youngest group of children (6-8 yr olds), prevalence of goiter decreased to 3.2%--i.e. below endemic levels.

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress

PubMed Central

Muratori, Monica; Tamburrino, Lara; Marchiani, Sara; Cambi, Marta; Olivito, Biagio; Azzari, Chiara; Forti, Gianni; Baldi, Elisabetta

2015-01-01

Sperm DNA fragmentation (sDF) represents a threat to male fertility, human reproduction and the health of the offspring. The causes of sDF are still unclear, even if apoptosis, oxidative assault and defects in chromatin maturation are hypothesized. Using multicolor flow cytometry and sperm sorting, we challenged the three hypothesized mechanisms by simultaneously evaluating sDF and signs of oxidative damage (8-hydroxy, 2′-deoxyguanosine [8-OHdG] and malondialdehyde [MDA]), apoptosis (caspase activity and cleaved poly[ADP-ribose] polymerase [cPARP]) and sperm immaturity (creatine phosphokinase [CK] and excess of residual histones). Active caspases and c-PARP were concomitant with sDF in a high percentage of spermatozoa (82.6% ± 9.1% and 53.5% ± 16.4%, respectively). Excess of residual histones was significantly higher in DNA-fragmented sperm versus sperm without DNA fragmentation (74.8% ± 17.5% and 37.3% ± 16.6%, respectively, p < 0.005), and largely concomitant with active caspases. Conversely, oxidative damage was scarcely concomitant with sDF in the total sperm population, at variance with live sperm, where 8-OHdG and MDA were clearly associated to sDF. In addition, most live cells with active caspase also showed 8-OHdG, suggesting activation of apoptotic pathways in oxidative-injured live cells. This is the first investigation on the origin of sDF directly evaluating the simultaneous presence of the signs of the hypothesized mechanisms with DNA breaks at the single cell level. The results indicate that the main pathway leading to sperm DNA breaks is a process of apoptosis, likely triggered by an impairment of chromatin maturation in the testis and by oxidative stress during the transit in the male genital tract. These findings are highly relevant for clinical studies on the effects of drugs on sDF and oxidative stress in infertile men and for the development of new therapeutic strategies. PMID:25786204

The relevance of the urinary concentration of ephedrines in anti-doping analysis: determination of pseudoephedrine, cathine, and ephedrine after administration of over-the-counter medicaments.

PubMed

Strano-Rossi, Sabina; Leone, Daniele; de la Torre, Xavier; Botrè, Francesco

2009-08-01

This article describes a method for the detection and quantitation of cathine, pseudoephedrine, ephedrine, and methylephedrine in urine, using their deuterated analogues as internal standards and derivatization to form the corresponding trimethylsilyl derivatives after a simple liquid-liquid extraction. The study was designed to evaluate whether the urinary cutoff values set by the World Anti-Doping Agency for the banned ephedrines (cathine >5 microg/mL, ephedrine and methylephedrine >10 microg/mL) can be exceeded after the normal self-administration of common over-the-counter medicaments containing nonbanned ephedrines. The present method, after validation, has been applied on real urine samples obtained from 9 healthy volunteers taking different doses of over-the-counter preparations containing ephedrines. Results obtained from excretion studies show high interindividual differences in the urinary concentrations of both pseudoephedrine and cathine, not dependent on body weight or sex nor, in some instances, on the administered dose. The same typical therapeutic dose of pseudoephedrine (60 mg) produced a urinary concentration of more than 5 microg/mL for cathine and of more than 100 microg/mL for pseudoephedrine in 2 of 9 subjects only. When a dose of 120 mg was administered, cathine concentration exceeded 5 microg/mL in 4 of 7 subject, and also concentrations of pseudoephedrine above 100 microg/mL. After administration of 5 x 120 mg of pseudoephedrine (120 mg administered every 7 days for 5 weeks) to one of the subjects exceeding the urinary threshold values, the urinary concentration of cathine and pseudoephedrine exceeded 5 microg/mL (peak concentration 14.8 microg/mL) and 100 microg/mL (peak concentration 275 microg/mL), respectively. When the same subject took 180 mg of pseudoephedrine, the urinary concentration values were below 5 microg/mL for ephedrine and 100 microg/mL for pseudoephedrine. In the case of ephedrine administration in a sustained-release formulation containing 12 mg of ephedrine, 2 of 3 subjects exceeded the urinary cutoff value of 10 microg/mL. The high interindividual variability is still significant even if the urinary concentration values are adjusted by specific gravity and/or creatinine. These results confirm a high interindividual variability in the urinary concentration of ephedrines after the administration of the same therapeutic dose of a preparation.

Cerebrospinal Fluid Concentration of Key Autophagy Protein Lamp2 Changes Little During Normal Aging

PubMed Central

Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.

2018-01-01

Autophagy removes both functional and damaged intracellular macromolecules from cells via lysosomal degradation. Three autophagic mechanisms, namely macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy, have been described in mammals. Studies in experimental systems have found macroautophagy and CMA to decrease with normal aging, despite the fact that oxidative stress, which can activate both processes, increases with normal aging. Whether autophagic mechanisms decrease in the human brain during normal aging is unclear. The primary objective of this study was to examine the association of a major autophagy protein, lysosome-associated membrane glycoprotein (lamp2), with age in cerebrospinal fluid (CSF) samples from healthy subjects. Lamp2 consists of three isoforms, lamp2a, 2b and 2c, all of which participate in autophagy. Lamp2’s CSF concentration decreases in Parkinson’s disease (PD) and increases in Alzheimer’s disease (AD), but whether its CSF concentration changes during normal aging has not been investigated. Our secondary objectives were to examine the associations of lamp2’s CSF concentration with CSF levels of the molecular chaperone heat shock 70-kDa protein (HSPA8), which interacts with lamp2a in CMA, and oxidative stress markers 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-isoprostane (8-ISO) and Total Antioxidant Capacity (TAC) in healthy subjects. We found lamp2’s observed associations with these variables to be weak, with all Kendall’s tau-b absolute values ≤0.20. These results suggest that CSF lamp2 concentration changes little during normal aging and does not appear to be associated with HSPA8 or oxidative stress. Further studies are indicated to determine the relationship between CSF lamp2 concentration and brain autophagic processes.

(2-methoxyethoxy)acetic acid: a urinary biomarker of exposure for jet fuel JP-8.

PubMed

B'hymer, Clayton; Mathias, Patricia; Krieg, Edward; Cheever, Kenneth L; Toennis, Christine A; Clark, John C; Kesner, James S; Gibson, Roger L; Butler, Mary Ann

2012-05-01

To demonstrate the utility of the urinary metabolite (2-methoxyethoxy)acetic acid (MEAA) as a biomarker of exposure. 2-(2-methoxyethoxy)ethanol [diethylene glycol monomethyl ether] is an anti-icing agent used in the formulation of JP-8, and it is added at a known uniform 0.1% (v/v) concentration to each batch lot. JP-8 is a kerosene-based fuel containing different compounds that vary in the content of every batch/lot of fuel; thus, MEAA has the potential to be a more specific and a consistent quantitative biomarker for JP-8 exposure. MEAA was used to measure exposure of jet propulsion fuel 8 (JP-8) in United States Air Force (USAF) personnel working at six airbases within the United States. Post-shift urine specimens from various personnel including high (n = 98), moderate (n = 38), and low (n = 61) exposure workgroup categories were collected and analyzed by a gas chromatographic-mass spectrometric test method. The three exposure groups were evaluated for the number per group positive for MEAA, and a statistical analysis consisted of pair-wise t-tests for unequal variances was used to test for the differences in mean MEAA concentrations between the exposure groups. The number of samples detected as positive for MEAA exposure, that is, those above the test method's limit of detection (LOD = 0.1 μg/ml), were 92 (93.9%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure workgroup categories, respectively. The mean urinary MEAA level was significantly greater in the high exposure category (6.8 μg/ml), compared to the moderate (0.42 μg/ml) and the low (0.07 μg/ml) exposure categories. The maximum concentration of urinary MEAA was 110 μg/ml for the high exposure category, while 4.8 μg/ml and 0.2 μg/ml maximum levels were found in the moderate and low exposure categories, respectively. This study demonstrated that urinary MEAA can be used as an accurate biomarker of exposure for JP-8 workers and clearly distinguished the differences in JP-8 exposure by workgroup category.

Urinary concentrations of acrylamide (AA) and N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and associations with demographic factors in the South Korean population.

PubMed

Lee, Jin Heon; Lee, Kee Jae; Ahn, Ryoungme; Kang, Hee Sook

2014-09-01

Acrylamide (AA) and N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) are important urinary biomarkers of acrylamide exposure in human biomonitoring, because AA is classified as a probable carcinogen in humans. In this study, urinary AA and AAMA were assessed in the South Korean adult population aged 18-69, based on the Korean National Human Biomonitoring Survey conducted in 2009. Urinary metabolites in samples were analyzed with LC-MS/MS system. Relying on data from 1873 representative South Korean adults, the population-weighted geometric means of urinary AA and AAMA concentrations were 6.8 ng/ml (95% CI: 6.4-7.3), and 30.0 ng/ml (95% confidence interval (CI): 28.2-31.8), respectively. The creatinine-adjusted geometric means of AA and AAMA were 6.2 μg/g creatinine (95% CI: 5.8-6.7) and 26.4μg/g creatinine (95% CI: 24.9-28.0), respectively. When covariates for predictors of urinary metabolites were adjusted simultaneously in a log-linear multiple regressions, the strongest predictors of urinary AA were education (OR=1.08-1.28; 95% CI: 1.11-1.48; p=0.0024) and age (OR=0.66-0.84; 95% CI: 0.54-0.97; p=0.0003), and those of urinary AAMA were smoking status (OR=1.16-2.63; 95% CI: 0.98-3.08; p=0.001) and education (OR=1.12-1.19; 95% CI: 1.02-1.38; p=0.0425). The ratio of current/never smokers for urinary AA was 1.3, whereas the same ratio for urinary AAMA was 3.0. These findings suggested that most South Koreans had detectable levels of AA and AAMA (98.7% and 99.4%, respectively) in their urine and that the body burden of AA and AAMA varied according to demographic, geographic, and lifestyle (smoking) factors. Copyright © 2014 Elsevier GmbH. All rights reserved.

Effect of different concentrations of dietary P and Ca on plasma inorganic P and urinary P excretion using noncolostomized and colostomized broilers.

PubMed

Manangi, Megharaja K; Maharjan, Pramir; Coon, Craig N

2018-02-01

Two 5-d bioassays were conducted to explore the P physiological threshold in broilers based on plasma inorganic P (iP), urinary P and Ca, and excreta P and Ca measurements in non-colostomized and colostomized broilers fed with different concentrations of non-phytate P (NPP) and Ca. In Experiment 1, 80 40-day-old Cobb 500 non-colostomized male broilers were assorted into 8 groups consisting of 10 broilers each and placed in individual metabolic cages. Similarly, 8 colostomized broilers of same age were allotted to 8 individual metabolic cages. The experimental diets consisted of a corn soybean meal basal containing 0.17% phytate P (PP) with 8 concentrations (0.08, 0.13, 0.18, 0.23, 0.28, 0.33, 0.38, and 0.45%) of NPP. The dietary Ca concentration was maintained at 0.5% by adjusting a 185-micron particle size limestone with each concentration of added P from added calcium phosphate, dibasic, monohydrate. After Experiment 1, broilers were fed a standard grower diet for 5 d and Experiment 2 was conducted the same as Experiment 1; however, Ca was maintained at 0.9% for all test diets. Plasma iP, urinary P and Ca, and total P (TP) and Ca retention along with phytate P hydrolysis were measured. At 0.5% Ca dietary level, the inflection points for dietary NPP obtained from segmented line regression analysis for plasma iP, urinary P, and urinary Ca were 0.26% (±0.04 SE), 0.28% (±0.01 SE), and 0.30% (±0.04 SE), respectively. The similar values for 0.9% Ca diets were 0.27% (±0.03 SE), 0.21% (±0.03 SE), and 0.30% (±0.0 SE), respectively. In summary, the present findings suggest that an increased dietary NPP would increase plasma inorganic P concentration along with increased % retention of TP and NPP until the broilers reach a point of physiological steady state (7.51 mg iP/dL - 8.13 mg iP/dL as found in this study). Excess P beyond physiological threshold is eliminated in urine coupled with decreased % retention. © 2017 Poultry Science Association Inc.

Part 3. Assessment of genotoxicity and oxidative stress after exposure to diesel exhaust from U.S. 2007-compliant diesel engines: report on 1- and 3-month exposures in the ACES bioassay.

PubMed

Hallberg, L M; Ward, J B; Hernandez, C; Ameredes, B T; Wickliffe, J K

2012-09-01

Human health hazards due to diesel exhaust (DE*) exposure have been associated with both solvent and combustion components. In the past, diesel engine exhaust components have been linked to increased mutagenicity in cultures of Salmonella typhimurium and mammalian cells (Tokiwa and Ohnishi 1986). In addition, DE has been shown to increase both the incidence of tumors and the induction of 8-hydroxy-deoxyguanosine adducts (8-OHdG) in ICR mice (Ichinose et al. 1997). Furthermore, DE is composed of a complex mixture of polycyclic aromatic hydrocarbons (PAHs) and particulates. One such PAH, 3-nitrobenzanthrone (3-NBA), has been identified in DE and found in urban air. 3-NBA has been observed to induce micronucleus formation in DNA of human hepatoma cells (Lamy et al. 2004). The purpose of the current research, which is part of the Advanced Collaborative Emissions Study (ACES), a multidisciplinary program being carried out by the Health Effects Institute and the Coordinating Research Council, is to determine whether improvements in the engineering of heavy-duty diesel engines reduce the oxidative stress and genotoxic risk associated with exposure to DE components. To this end, the genotoxicity and oxidative stress of DE from an improved diesel engine was evaluated in bioassays of tissues from Wistar Han rats and C57BL/6 mice exposed to DE. Genotoxicity was measured as strand breaks using an alkaline-modified comet assay. To correlate possible DNA damage found by the comet assay, measurement of DNA-adduct formation was evaluated by a competitive enzyme-linked immunosorbent assay (ELISA) to determine the levels of free 8-OHdG found in the serum of the animals exposed to DE. 8-OHdG is a specific modified base indicating an oxidative type of DNA damage to DNA nucleotides. In addition, a thiobarbituric acid reactive substances (TBARS) assay was used to assess oxidative stress and damage in the form of lipid peroxidation in the hippocampus region of the brains of DE-exposed animals. Results from the comet assay showed no significant differences in rats between the control and exposed groups (P = 0.53, low exposure; P = 0.92, medium exposure; P = 0.77, high exposure) after 1 month of DE exposure. There were no differences between sexes in the responses of rats to these exposures. Likewise, there were no significant differences found after 3 months of exposure. Similarly, no significant differences were found between the mice exposed for 1 and 3 months to DE, nor were any differences found between sexes. Measurements of 8-OHdG in both mice and rats showed no significant difference among DE exposure groups (P = 0.46, mice; P = 0.86, rats). In mice, measured 8-OHdG was lower in the 3-month group than the 1-month group. In rats, the inverse was true. In mice, no significant differences in the levels of lipid peroxidation, as measured by TBARS, were found between the controls and DE exposure groups (P = 0.92), nor were there any differences between sexes. In rats, comparisons between the control and low-exposure groups approached significance, but no significant differences were found between the other DE exposure groups. Additionally, in rats, there were no significant differences between the 1- and 3-month DE exposure groups.

Cardiorespiratory Biomarker Responses in Healthy Young Adults to Drastic Air Quality Changes Surrounding the 2008 Beijing Olympics

PubMed Central

Zhang, Junfeng; Zhu, Tong; Kipen, Howard; Wang, Guangfa; Huang, Wei; Rich, David; Zhu, Ping; Wang, Yuedan; Lu, Shou-En; Ohman-Strickland, Pamela; Diehl, Scott; Hu, Min; Tong, Jian; Gong, Jicheng; Thomas, Duncan

2014-01-01

Associations between air pollution and cardiorespiratory mortality and morbidity have been well established, but data to support biologic mechanisms underlying these associations are limited. We designed this study to examine several prominently hypothesized mechanisms by assessing Beijing residents’ biologic responses, at the biomarker level, to drastic changes in air quality brought about by unprecedented air pollution control measures implemented during the 2008 Beijing Olympics. To test the hypothesis that changes in air pollution levels are associated with changes in biomarker levels reflecting inflammation, hemostasis, oxidative stress, and autonomic tone, we recruited and retained 125 nonsmoking adults (19 to 33 years old) free of cardiorespiratory and other chronic diseases. Using the combination of a quasi-experimental design and a panel-study approach, we measured biomarkers of autonomic dysfunction (heart rate [HR*] and heart rate variability [HRV]), of systemic inflammation and oxidative stress (plasma C-reactive protein [CRP], fibrinogen, blood cell counts and differentials, and urinary 8-hydroxy-2′-deoxyguanosine [8-OHdG]), of pulmonary inflammation and oxidative stress (fractional exhaled nitric oxide [FeNO], exhaled breath condensate [EBC] pH, EBC nitrate, EBC nitrite, EBC nitrite+nitrate [sum of the concentrations of nitrite and nitrate], and EBC 8-isoprostane), of hemostasis (platelet activation [plasma sCD62P and sCD40L], platelet aggregation, and von Willebrand factor [vWF]), and of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). These biomarkers were measured on each subject twice before, twice during, and twice after the Beijing Olympics. For each subject, repeated measurements were separated by at least one week to avoid potential residual effects from a prior measurement. We measured a large suite of air pollutants (PM2.5 [particulate matter ≤ 2.5 μm in aerodynamic diameter] and constituents, sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and ozone [O3]) throughout the study at a central Beijing site near the residences and workplaces of the subjects on a daily basis. Total particle number (TPN) was also measured at a separate site. We used a time-series analysis to assess changes in pollutant concentration by period (pre-, during-, and post-Olympics periods). We used mixed-effects models to assess changes in biomarker levels by period and to estimate changes associated with increases in pollutant concentrations, controlling for ambient temperature, relative humidity (RH), sex, and the day of the week of the biomarker measurements. We conducted sensitivity analyses to assess the impact of potential temporal confounding and exposure misclassification. We observed reductions in mean concentrations for all measured pollutants except O3 from the pre-Olympics period to the during-Olympics period. On average, elemental carbon (EC) changed by −36%, TPN by −22%, SO2 by −60%, CO by −48%, and NO2 by −43% (P < 0.05 for all these pollutants). Reductions were observed in mean concentrations of PM2.5 (by −27%), sulfate (SO42−) (by −13%), and organic carbon (OC) (by −23%); however, these values were not statistically significant. Both 24-hour averages and 1-hour maximums of O3 increased (by 20% and 17%, respectively) from the pre-Olympics to the during-Olympics period. In the post-Olympics period after the pollution control measures were relaxed, mean concentrations of most pollutants (with the exception of SO42− and O3) increased to levels similar to or higher than pre-Olympics levels. Concomitantly and consistent with the hypothesis, we observed, from the pre-Olympics to the during-Olympics period, statistically significant (P ≤ 0.05) or marginally significant (0.05 < P < 0.1) decreases in HR (−1 bpm or −1.7% [95% CI, −3.4 to −0.1]), SBP (−1.6 mmHg or − 1.8% [95% CI, −3.9 to 0.4]), 8-OHdG (−58.3% [95% CI, −72.5 to −36.7]), FeNO (−60.3% [95% CI, −66.0 to −53.6]), EBC nitrite (−30.0% [95% CI, −39.3 to −19.3]), EBC nitrate (−21.5% [95% CI, −35.5 to −4.5]), EBC nitrite+nitrate (−17.6% [95% CI, −28.4 to −5.1]), EBC hydrogen ions (−46% [calculated from EBC pH], or +3.5% in EBC pH [95% CI, 2.2 to 4.9]), sCD62P (−34% [95% CI, −38.4 to −29.2]), sCD40L (−5.7% [95% CI, −10.5 to −0.7]), and vWF (−13.1% [95% CI, −18.6 to −7.5]). Moreover, the percentages of above-detection values out of all observations were significantly lower for plasma CRP and EBC 8-isoprostane in the during-Olympics period compared with the pre-Olympics period. In the post-Olympics period, the levels of the following biomarkers reversed (increased, either with or without statistical significance) from those in the during-Olympics period: SBP (10.7% [95% CI, 2.8 to 18.6]), fibrinogen (4.3% [95% CI, −1.7 to 10.2), neutrophil count (4.7% [95% CI, −7.7 to 17.0]), 8-OHdG (315% [95% CI, 62.0 to 962]), FeNO (130% [95% CI, 62.5 to 225]), EBC nitrite (159% [95% CI, 71.8 to 292]), EBC nitrate (161% [95% CI, 48.0 to 362]), EBC nitrite+nitrate (124% [95% CI, 50.9 to 233]), EBC hydrogen ions (146% [calculated from EBC pH] or −4.8% in EBC pH [95% CI, −9.4 to −0.2]), sCD62P (33.7% [95% CI, 17.7 to 51.8]), and sCD40L (9.1% [95% CI, −3.7 to 23.5]). Furthermore, these biomarkers also showed statistically significant associations with multiple pollutants across different lags after adjusting for meteorologic parameters. The associations were in the directions hypothesized and were consistent with the findings from the comparisons between periods, providing further evidence that the period effects were due to changes in air quality, independent of season and meteorologic conditions or other potential confounders. Contrary to our hypothesis, however, we observed increases in platelet aggregation, red blood cells (RBCs) and white blood cells (WBCs) associated with the during-Olympics period, as well as significant negative associations of these biomarkers with pollutant concentrations. We did not observe significant changes in any of the HRV indices and DBP by period. However, we observed associations between a few HRV indices and pollutant concentrations. Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of pulmonary and systemic inflammation, oxidative stress, and hemostasis and in measures of cardiovascular physiology (HR and SBP) in healthy, young adults. These changes support the prominently hypothesized mechanistic pathways underlying the cardiorespiratory effects of air pollution. PMID:23646463

Cardiorespiratory biomarker responses in healthy young adults to drastic air quality changes surrounding the 2008 Beijing Olympics.

PubMed

Zhang, Junfeng; Zhu, Tong; Kipen, Howard; Wang, Guangfa; Huang, Wei; Rich, David; Zhu, Ping; Wang, Yuedan; Lu, Shou-En; Ohman-Strickland, Pamela; Diehl, Scott; Hu, Min; Tong, Jian; Gong, Jicheng; Thomas, Duncan

2013-02-01

Associations between air pollution and cardiorespiratory mortality and morbidity have been well established, but data to support biologic mechanisms underlying these associations are limited. We designed this study to examine several prominently hypothesized mechanisms by assessing Beijing residents' biologic responses, at the biomarker level, to drastic changes in air quality brought about by unprecedented air pollution control measures implemented during the 2008 Beijing Olympics. To test the hypothesis that changes in air pollution levels are associated with changes in biomarker levels reflecting inflammation, hemostasis, oxidative stress, and autonomic tone, we recruited and retained 125 nonsmoking adults (19 to 33 years old) free of cardiorespiratory and other chronic diseases. Using the combination of a quasi-experimental design and a panel-study approach, we measured biomarkers of autonomic dysfunction (heart rate [HR*] and heart rate variability [HRV]), of systemic inflammation and oxidative stress (plasma C-reactive protein [CRP], fibrinogen, blood cell counts and differentials, and urinary 8-hydroxy-2'-deoxyguanosine [8-OHdG]), of pulmonary inflammation and oxidative stress (fractional exhaled nitric oxide [FeNO], exhaled breath condensate [EBC] pH, EBC nitrate, EBC nitrite, EBC nitrite+nitrate [sum of the concentrations of nitrite and nitrate], and EBC 8-isoprostane), of hemostasis (platelet activation [plasma sCD62P and sCD40L], platelet aggregation, and von Willebrand factor [vWF]), and of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). These biomarkers were measured on each subject twice before, twice during, and twice after the Beijing Olympics. For each subject, repeated measurements were separated by at least one week to avoid potential residual effects from a prior measurement. We measured a large suite of air pollutants (PM2.5 [particulate matter < or = 2.5 microm in aerodynamic diameter] and constituents, sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and ozone [O3]) throughout the study at a central Beijing site near the residences and workplaces of the subjects on a daily basis. Total particle number (TPN) was also measured at a separate site. We used a time-series analysis to assess changes in pollutant concentration by period (pre-, during-, and post-Olympics periods). We used mixed-effects models to assess changes in biomarker levels by period and to estimate changes associated with increases in pollutant concentrations, controlling for ambient temperature, relative humidity (RH), sex, and the day of the week of the biomarker measurements. We conducted sensitivity analyses to assess the impact of potential temporal confounding and exposure misclassification. We observed reductions in mean concentrations for all measured pollutants except O3 from the pre-Olympics period to the during-Olympics period. On average, elemental carbon (EC) changed by -36%, TPN by -22%, SO2 by -60%, CO by -48%, and NO2 by -43% (P < 0.05 for all these pollutants). Reductions were observed in mean concentrations of PM2.5 (by -27%), sulfate (SO4(2-)) (by -13%), and organic carbon (OC) (by -23%); however, these values were not statistically significant. Both 24-hour averages and 1-hour maximums of O3 increased (by 20% and 17%, respectively) from the pre-Olympics to the during-Olympics period. In the post-Olympics period after the pollution control measures were relaxed, mean concentrations of most pollutants (with the exception of SO4(2-) and O3) increased to levels similar to or higher than pre-Olympics levels. Concomitantly and consistent with the hypothesis, we observed, from the pre-Olympics to the during-Olympics period, statistically significant (P < or = 0.05) or marginally significant (0.05 < P < 0.1) decreases in HR (-1 bpm or -1.7% [95% CI, -3.4 to -0.1]), SBP (-1.6 mmHg or -1.8% [95% CI, -3.9 to 0.4]), 8-OHdG (-58.3% [95% CI, -72.5 to -36.7]), FeNO (-60.3% [95% CI, -66.0 to -53.6]), EBC nitrite (-30.0% [95% CI, -39.3 to -19.3]), EBC nitrate (-21.5% [95% CI, -35.5 to -4.5]), EBC nitrite+nitrate (-17.6% [95% CI, -28.4 to -5.1]), EBC hydrogen ions (-46% [calculated from EBC pH], or +3.5% in EBC pH [95% CI, 2.2 to 4.9]), sCD62P (-34% [95% CI, -38.4 to -29.2]), sCD40L (-5.7% [95% CI, -10.5 to -0.7]), and vWF (-13.1% [95% CI, -18.6 to -7.5]). Moreover, the percentages of above-detection values out of all observations were significantly lower for plasma CRP and EBC 8-isoprostane in the during-Olympics period compared with the pre-Olympics period. In the post-Olympics period, the levels of the following biomarkers reversed (increased, either with or without statistical significance) from those in the during-Olympics period: SBP (10.7% [95% CI, 2.8 to 18.6]), fibrinogen (4.3% [95% CI, -1.7 to 10.2), neutrophil count (4.7% [95% CI, -7.7 to 17.0]), 8-OHdG (315% [95% CI, 62.0 to 962]), FeNO (130% [95% CI, 62.5 to 225]), EBC nitrite (159% [95% CI, 71.8 to 292]), EBC nitrate (161% [95% CI, 48.0 to 362]), EBC nitrite+nitrate (124% [95% CI, 50.9 to 233]), EBC hydrogen ions (146% [calculated from EBC pH] or -4.8% in EBC pH [95% CI, -9.4 to -0.21), sCD62P (33.7% [95% CI, 17.7 to 51.8]), and sCD40L (9.1% [95% CI, -3.7 to 23.5]). Furthermore, these biomarkers also showed statistically significant associations with multiple pollutants across different lags after adjusting for meteorologic parameters. The associations were in the directions hypothesized and were consistent with the findings from the comparisons between periods, providing further evidence that the period effects were due to changes in air quality, independent of season and meteorologic conditions or other potential confounders. Contrary to our hypothesis, however, we observed increases in platelet aggregation, red blood cells (RBCs) and white blood cells (WBCs) associated with the during-Olympics period, as well as significant negative associations of these biomarkers with pollutant concentrations. We did not observe significant changes in any of the HRV indices and DBP by period. However, we observed associations between a few HRV indices and pollutant concentrations. Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of pulmonary and systemic inflammation, oxidative stress, and hemostasis and in measures of cardiovascular physiology (HR and SBP) in healthy, young adults. These changes support the prominently hypothesized mechanistic pathways underlying the cardiorespiratory effects of air pollution.

Behavior of heavy metals in human urine and blood following calcium disodium ethylenediamine tetraacetate injection: observations in metal workers.

PubMed

Sata, F; Araki, S; Murata, K; Aono, H

1998-06-12

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the "circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.

Oxidative damage of workers in secondary metal recovery plants affected by smoking status and joining the smelting work.

PubMed

Chia, Taipau; Hsu, Ching Yi; Chen, Hsiu Ling

2008-04-01

In Taiwan, secondary copper smelters and zinc recovery plants primarily utilize recovering metal from scrap and dross, and handles mostly fly ash and slag with high temperature to produce ZnO from the iron and steel industry. The materials may contain organic impurities, such as plastic and organic chloride chemicals, and amounts of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) are produced during the smelting process. Therefore, secondary metal recovery industries are major emission sources of PCDD/Fs, which may have been demonstrated to elicit oxidative stress and to involve the production of plasma malondialdehyde (MDA). Many studies have also indicated that the intake of antioxidants, smoking, age and exposure to environmental pollutants may be implicated to DNA damage or lipid peroxidation. This study therefore aims to elucidate the roles of occupational exposure like joining the smelting work, age, smoking and alcohol status, and antioxidant intake on oxidative damage in secondary metal recovery workers in Taiwan. 73 workers were recruited from 2 secondary metal recovery plants. The analysis of 8-hydroxydeoxyguanosine (8-OH-dG) in urine, DNA strand breakage (comet assay) and lipid peroxidation (MDA) in blood samples were completed for all of the workers. The results showed that the older subjects exhibited significantly lower levels of 8-OH-dG and MDA than younger subjects. Our investigation also showed that working departments were in related to plasma MDA and DNA strand breakage levels of nonsmokers, however, the observation become negligible in smokers. And it is implicated that cigarette type might affect 8-OH-dG levels in secondary metal recovery workers. Since, adding to results above, the MDA level in production workers was significantly higher than those in managerial departments, it is important for the employers to make efforts on improving occupational environments or serving protective equipments to protect workers in secondary metal recovery factories.

Oxidative stress markers in saliva and periodontal disease status: modulation during pregnancy and postpartum.

PubMed

Gümüş, Pınar; Emingil, Gülnur; Öztürk, Veli-Özgen; Belibasakis, Georgios N; Bostanci, Nagihan

2015-07-08

Periodontal diseases may affect local and systemic inflammation, and reactive oxygen species (ROS) levels. This systemic health burden could compromise the outcome of pregnancy in expectant mothers. The aim of the present study was to evaluate oxidative stress markers, including glutathione peroxidase (GPx), thiobarbituric acid-reactive substances (TBARS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and total bacterial loads in the saliva of pregnant and postpartum women, and to investigate their association with periodontal disease severity. A total of 187 women were originally recruited for this case-control study, assigned to the following groups a) pregnant group, b) postpartum group: the pregnant group re-evaluated 6 months after giving birth, c) control group: systemically healthy and non-pregnant women. The levels of the studied oxidative stress markers in saliva were measured by commercially available kits. The levels of salivary 8-OHdG were significantly elevated in the pregnant, compared with the control group. Although salivary 8-OHdG levels slightly decreased after giving birth (postpartum group), the difference did not reach significance. In contrast, the activity of antioxidant enzyme GPx in saliva was significantly lower in the pregnant than the control group. Although no differences in lipid peroxidation (represented by TBARS) were observed between the pregnant and control groups, after giving birth TBARS levels were significantly lowered. Only in the postpartum and control groups did clinical measurements of periodontal disease severity correlate with oxidative stress markers. Interestingly, there were no such correlations with TBARS in the pregnant and postpartum groups. The present study shows changes in the oxidant/antioxidant balance in saliva during pregnancy and after birth, which may be affected by periodontal health status in the latter case. Whether this is associated with adverse pregnancy outcomes, or not, remains to be elucidated. Early identification of ROS markers in saliva may be of clinical value in the periodontal management of pregnant women.

The Importance of Urine Concentration on the Diagnostic Performance of the Urinalysis for Pediatric Urinary Tract Infection.

PubMed

Chaudhari, Pradip P; Monuteaux, Michael C; Shah, Pinkey; Bachur, Richard G

2017-07-01

The presence of leukocyte esterase by urine dipstick and microscopic pyuria are both indicators of possible urinary tract infection. The effect of urine concentration on the diagnostic performance of the urinalysis for pediatric urinary tract infection has not been studied. Our objective is to determine whether the urinalysis performance for detecting urinary tract infection varies by urine concentration as measured by specific gravity. This was a retrospective cross-sectional study of the urine laboratory results of children younger than 13 years who presented to the emergency department during 68 months and had a paired urinalysis and urine culture obtained. Urinary tract infection was defined as pure growth of a uropathogen at standard culture thresholds. Test characteristics were calculated across 4 specific gravity groups (1.000 to 1.010, 1.011 to 1.020, 1.021 to 1.030, and >1.030). In total, 14,971 cases were studied. Median age was 1.5 years (interquartile range 0.4 to 5.5 years) and 60% were female patients. Prevalence of urinary tract infection was 7.7%. For the presence of leukocyte esterase and a range of pyuria cut points, the positive likelihood ratios decreased with increasing specific gravity. From most dilute to most concentrated urine, the positive likelihood ratio decreased from 12.1 (95% confidence interval [CI] 10.7 to 13.7) to 4.2 (95% CI 3.0 to 5.8) and 9.5 (95% CI 8.6 to 10.6) to 5.5 (95% CI 3.3 to 9.1) at a threshold of greater than or equal to 5 WBCs per high-power field and presence of leukocyte esterase, respectively. The negative likelihood ratios increased with increasing specific gravity for leukocyte esterase and microscopic pyuria. For the detection of pediatric urinary tract infection, the diagnostic performance of both dipstick leukocyte esterase and microscopic pyuria varies by urine concentration, and therefore the specific gravity should be considered when the urinalysis is interpreted. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice.

PubMed

Ohguchi, Takeshi; Kojima, Takashi; Ibrahim, Osama M; Nagata, Taeko; Shimizu, Takahiko; Shirasawa, Takuji; Kawakita, Tetsuya; Satake, Yoshiyuki; Tsubota, Kazuo; Shimazaki, Jun; Ishida, Susumu

2013-11-21

To investigate the efficacy of 2% rebamipide ophthalmic solution on the tear functions and ocular surface status of the superoxide dismutase-1(Sod1(-/-)) mice. Two percent Rebamipide ophthalmic solution was applied to 40-week-old male Sod1(-/-) and wild-type (WT) mice four times a day for 2 weeks. We examined the cytokine concentrations in the tear fluid (by CytoBead assay), tear film break-up time, amount of tear production, and expressions of mucins 1, 4, and 5AC, by RT-PCR. We also performed vital staining of the ocular surface, PAS staining for muc5AC, and immunohistochemical stainings for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2'-deoxyguanosine (8-OHdG), in the conjunctiva to compare the results before and after rebamipide instillations. The tear functions and ocular surface epithelial damage scores were significantly worse in the Sod1(-/-) than in the WT mice. Application of 2% rebamipide for 2 weeks significantly improved the tear film break-up time, the amount of tear production, and the corneal epithelial damage scores, which also significantly increased the conjunctival goblet cell density and muc5 mRNA expression, in the Sod1(-/-) mice. The mean IL-6, IL-17, TNF-α, and IFN-γ levels in the tear fluid were reduced significantly along with a significant decrease in the density of cells positive for 4-HNE and 8-OHdG in the conjunctiva. Two percent Rebamipide ophthalmic solution significantly improved the tear stability and corneal epithelial damage, and enhanced the expression of muc5 mRNA on the ocular surface. We also observed anti-inflammatory effects in the tear film together with antioxidative effects in the conjunctiva, suggesting the efficacy of rebamipide in age-related dry eye disease attributable to SOD1 knockout.

Effect of di(n-butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid rats.

PubMed

Lee, Ena; Ahn, Mee Young; Kim, Hee Jin; Kim, In Young; Han, Soon Young; Kang, Tae Seok; Hong, Jin Hwan; Park, Kui Lea; Lee, Byung Mu; Kim, Hyung Sik

2007-06-01

This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 microg/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor alpha-1 (TRalpha-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP.

Increased Oxidative Stress in Healthy Children Following an Exercise Program: A Pilot Study

PubMed Central

Nasca, Melita M.; Zhang, Renliang; Super, Dennis M.; Hazen, Stanley L.; Hall, Howard R.

2010-01-01

Exercise can induce oxidative stress or an imbalance between reactive oxygen species and cellular antioxidant defenses. Objective We investigated the effect of a real-life exercise program on systemic oxidative stress measured by urinary concentrations of 8-isoprostaglandin F2α (8-iso-PGF2α), a noninvasive index of lipid peroxidation, in a well-characterized pediatric group. Methods Healthy but primarily sedentary, 8- to 10-year-old children (n = 6, mean age 8.8 ± 0.9 years) of equally distributed healthy weight, overweight, and obese categories, participated in a 5-week exercise program (track and field summer camp, 2 hours/day, 1–2 days/week). Results By using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS), we found a significant (p = .028) increase in group mean urinary 8-iso-PGF2α concentration from 8.163 ± 6.919 ng/mg creatinine pre-exercise program to 32.320 ± 16.970 ng/mg creatinine post-exercise program. The increase was also measured at each individual level. We found preliminary evidence that pre- and post-exercise program urinary 8-iso-PGF2α concentrations selectively correlated with children’s cardiometabolic characteristics and mood. Conclusion Our results warrant further exploration of the relationships between pre/post-exercise oxidative stress marker 8-iso-PGF2α and cardiometabolic characteristics, exercise habits, eating habits, and mood to determine whether increased post-exercise oxidative stress in healthy children is part of their normal adaptation to exercise or mediator of oxidative injury. PMID:20495476

Effects of zinc oxide nanoparticles on human coronary artery endothelial cells.

PubMed

Chuang, Kai-Jen; Lee, Kang-Yun; Pan, Chih-Hong; Lai, Ching-Huang; Lin, Lian-Yu; Ho, Shu-Chuan; Ho, Kin-Fai; Chuang, Hsiao-Chi

2016-07-01

Inhalation of zinc oxide (ZnO) metal fumes is known to cause metal fume fever and to have systemic effects; however, the effects of ZnO nanoparticles (ZnONPs) on the cardiovascular system remain unclear. The objective of this study was to investigate the cardiovascular toxicity of ZnONPs. Human coronary artery endothelial cells (HCAECs) were exposed to ZnONPs of different sizes to investigate the cell viability, 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin (IL)-6, nitric oxide (NO), and regulation of cardiovascular disease-related genes. Exposure of HCAECs to ZnONPs resulted in decreased cell viability and increased levels of 8-OHdG, IL-6, and NO. Downregulation of cardiovascular-associated genes was observed in response to ZnONPs in HCAECs determined by qPCR, suggesting that the calcium signaling pathway, neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, dilated cardiomyopathy, and renin-angiotensin system are important affected pathways in response to ZnONPs. Furthermore, we observed a significant response of AGTR1 to ZnONP exposure in HCAECs. Our results suggest that ZnONPs cause toxicity to HCAECs, which could be associated with cardiovascular dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Zinc Supplementation on DNA Damage in Rats with Experimental Kidney Deficiency.

PubMed

Yegin, Sevim Çiftçi; Dede, Semiha; Mis, Leyla; Yur, Fatmagül

2017-04-01

This study was carried out to determine the effect of zinc on oxidative DNA damage in rats with experimental acute and chronic kidney deficiency. Six groups of five Wistar-Albino rats each were assigned as controls (C), acute kidney deficiency (AKD), zinc-supplemented (+Zn), acute kidney deficiency, zinc-supplemented (AKD + Zn), chronic kidney deficiency (CKD) and zinc-supplemented chronic kidney deficiency (CKD + Zn). The levels of 8-Oxo-2'-deoxyguanosine (8-OHdG) were determined, being the lowest in the CKD group (p < 0.05), higher in the C group than those of rats with CKD but lower than that of all the other groups (p < 0.05). There were no significant differences between the controls and the CKD + Zn group, or between the AKD and the +Zn groups. Among all groups, the highest 8-OHdG level was found in the AKD + Zn group (p < 0.05). DNA damage was greater in acute renal failure than in rats with chronic renal failure. The DNA damage in the zinc group was significantly higher than in the controls.

Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands.

PubMed

Knaś, M; Maciejczyk, M; Daniszewska, I; Klimiuk, A; Matczuk, J; Kołodziej, U; Waszkiel, D; Ładny, J R; Żendzian-Piotrowska, M; Zalewska, A

2016-01-01

Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions.

Subjective Positive and Negative Sleep Variables Differentially Affect Cellular Immune Activity in a Breast Cancer Survivor: A Time-series Analysis Approach.

PubMed

Singer, Magdalena; Burbaum, Christina; Fritzsche, Kurt; Peterlini, Sylvia; Bliem, Harald R; Ocaña-Peinado, Francisco M; Fuchs, Dietmar; Schubert, Christian

2017-01-01

This study on a breast cancer survivor suffering from cancer-related fatigue (CaRF) and depression investigated the bidirectional relationship between cellular immune activity and subjective sleep. The 49-year-old patient (breast cancer diagnosis 5 years before the study, currently in remission) collected her full urine output for 28 days in 12-h intervals (8:00 p.m. to 8:00 a.m. and 8:00 a.m. to 8:00 p.m.). These urine samples were used to determine urinary neopterin (cellular immune activation marker) and creatinine concentrations via high-pressure liquid chromatography (HPLC). Each morning, the patient answered questions on five sleep variables: sleep quality (SQ), sleep recreational value (SRV), total sleep time (TST), total wake time (TWT), and awakenings during sleep period (ADS). For the purpose of this study, the time series of the nighttime urinary neopterin levels and the five sleep variables were determined. Using centered moving average (CMA) smoothing and cross-correlational analysis, this study showed that increases in the positive sleep variables SQ and SRV were followed by urinary neopterin concentration decreases after 96-120 h (SQ, lag 4: r  = -0.411; p  = 0.044; SRV: lag 4: r  = -0.472; p  = 0.021) and 120-144 h (SRV, lag 5: r  = -0.464; p  = 0.026). Increases in the negative sleep variable TWT, by contrast, were followed by increases in urinary neopterin concentrations 72-96 h later (lag 3: r  = 0.522; p  = 0.009). No systematic effects in the other direction, i.e., from urinary neopterin levels to sleep, were observed in this study. Although preliminary, the findings of this study highlight the benefit of carefully investigating temporal delays and directions of effects when studying the dynamic relationship between sleep and immune variables in the natural context of everyday life.

Post-fertilization effect of bilateral primary testicular damage induced by unilateral cryptorchidism in the rat model.

PubMed

Tsounapi, P; Honda, M; Dimitriadis, F; Shimizu, S; Hikita, K; Muraoka, K; Sejima, T; Saito, M; Tomita, S; Sofikitis, N; Takenaka, A

2016-03-01

Cryptorchidism, a common anomaly of the male genitalia, affects 2-4% of male infants. The post-fertilization effects of unilateral cryptorchidism model in the rat and the effects of antioxidant treatment were investigated. Six-week-old male Wistar rats were randomly separated into four groups. Unilateral cryptorchidism was induced in the right testis of three groups. One group was treated with saline intraperitoneally (i.p.) (Crypto), one group was treated with taurine (500 mg/kg, i.p.; Tau), and another group was treated with sivelestat (15 mg/kg i.p.; Siv). The control group was treated with saline i.p. The treatment was daily for 8 weeks. Five days before sacrifice, mating studies were performed. Body, testicular, and epididymal weights were recorded. Malondialdehyde (MDA) levels in the seminal vesicular fluid (SVF) were measured. Testicular levels of MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined bilaterally. TUNEL assay was used to examine DNA fragmentation bilaterally. Histological examination and the Johnsen score were used to evaluate morphological testicular alterations. The Crypto group demonstrated significantly lower right testicular and epididymal weights, significantly increased SVF-MDA levels, testicular MDA and 8-OHdG levels, and the apoptotic score bilaterally compared to the controls. Furthermore, histological evaluation revealed significantly reduced spermatogenesis and mild injury to the cryptorchid testes compared to the control. Treatment with both taurine and sivelestat significantly reduced SVF-MDA levels, testicular MDA, 8-OHdG, and apoptosis bilaterally compared to the Crypto group. Antioxidant treatment was unable to ameliorate spermatogenesis. Newborns delivered by females that mated with Crypto-males had significantly lower body weight compared with the respective animals from the control, Tau and Siv groups. The present study demonstrated that unilateral cryptorchidism-induced testicular damage can significantly affect the contralateral testis as well having further deleterious post-fertilization effect on the development of newborns. Treatment with antioxidants can partially improve the testicular damage bilaterally with beneficial effects for the newborns. © 2016 American Society of Andrology and European Academy of Andrology.

Association of expired nitric oxide with urinary metal concentrations in boilermakers exposed to residual oil fly ash.

PubMed

Kim, Jee Young; Hauser, Russ; Wand, Matthew P; Herrick, Robert F; Houk, R S; Aeschliman, David B; Woodin, Mark A; Christiani, David C

2003-11-01

Exposure to metal-containing particulate matter has been associated with adverse pulmonary responses. Metals in particulate matter are soluble, hence are readily recovered in urine of exposed individuals. This study investigated the association between urinary metal concentrations and the fractional concentration of expired nitric oxide (F(E)NO) in boilermakers (N = 32) exposed to residual oil fly ash (ROFA). Subjects were monitored at a boiler overhaul site located in the New England area, USA. F(E)NO and urine samples were collected pre- and post-workshift for 5 consecutive workdays. Metals investigated included vanadium (V), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), and lead (Pb). The median F(E)NO was 7.5 ppb (95% CI: 7.4-8.0), and the median creatinine-adjusted urinary metal concentrations (mug/g creatinine) were: vanadium, 1.37; chromium, 0.48; manganese, 0.30; nickel, 1.52; copper, 3.70; and lead, 2.32. Linear mixed-effects models indicated significant inverse exposure-response relationships between log F(E)NO and the log-transformed urinary concentrations of vanadium, manganese, nickel, copper, and lead at several lag times, after adjusting for smoking status. Urine samples may be utilized as a biomarker of occupational metal exposure. The inverse association between F(E)NO and urinary metal concentrations suggests that exposure to metals in particulate matter may have an adverse effect on respiratory health. Copyright 2003 Wiley-Liss, Inc.

In the search for reliable biomarkers for the early diagnosis of autism spectrum disorder: the role of vitamin D.

PubMed

El-Ansary, Afaf; Cannell, John J; Bjørklund, Geir; Bhat, Ramesa Shafi; Al Dbass, Abeer M; Alfawaz, Hanan A; Chirumbolo, Salvatore; Al-Ayadhi, Laila

2018-06-01

Autism spectrum disorder (ASD) affects about 1% of the world's population. Vitamin D is thought to be essential for normal brain development and modulation of the immune system. Worldwide about 1 billion people are affected by vitamin D deficiency. High-sensitivity C-reactive protein (hs-CRP), cytochrome P450 2E1 (CYP2E1) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) are biomarkers related to inflammation and oxidative stress. In the present study, these biomarkers were together with serum 25-hydroxyvitamin D (25(OH)D 3 ) analyzed in 28 (mean age seven years) Saudi male patients with ASD. The study was conducted to determine if there is any relationship between vitamin D levels, the tested biomarkers and the presence and severity of ASD. The hope was to identify if these biomarkers may be useful for early ASD diagnosis. The Childhood Autism Rating Scale (CARS) and the Social Responsiveness Scale (SRS) were used to measure autism severity. The results of the ASD children were compared with 27 age and gender-matched neurotypical controls. The data indicated that Saudi patients with ASD have significantly lower plasma levels of 25(OH)D 3 than neurotypical controls (38 ng/ml compared to 56 ng/ml, respectively; [P = 0.001]). Surprisingly, the levels of CYP2E1 were lower in the children with ASD than the neurotypical controls (0.48 ± 0.08 vs. 69 ± 0.07 ng/ml, respectively; P = 0.001). The ASD children also had significantly higher levels of hs-CRP (0.79 ± 0.09 vs. 0.59 ± 0.09 ng/ml, respectively; P = 0.001) and 8-OH-dG (8.17 ± 1.04 vs. 4.13 ± 1.01 ng/ml, respectively; P = 0.001, compared to neurotypical age and gender-matched controls. The values for hs-CRP and 8-OH-dG did not correlate [P < 0.001] with autism severity. There was found a relationship between autism severity on the CARS scale and the levels of 25(OH)D 3 and CYP1B1. But this was not found for SRS. All four biomarkers seemed to have good sensitivity and specificity, but the sample size of the present study was too small to determine clinical usefulness. The findings also indicate that inadequate levels of vitamin D play a role in the etiology and severity of autism. Furthermore, the results of the present study suggest the possibility of using 25(OH)D 3 , CYP1B1, hs-CRP and 8-OH-dG, preferably in combination, as biomarkers for the early diagnosis of ASD. However, further research is needed to evaluate this hypothesis.

Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women.

PubMed

Melzer, David; Osborne, Nicholas J; Henley, William E; Cipelli, Riccardo; Young, Anita; Money, Cathryn; McCormack, Paul; Luben, Robert; Khaw, Kay-Tee; Wareham, Nicholas J; Galloway, Tamara S

2012-03-27

The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors. We included 758 incident coronary artery disease (CAD) cases and 861 controls followed for 10.8 years from the European Prospective Investigation of Cancer-Norfolk UK. Respondents aged 40 to 74 years and free of CAD, stroke, or diabetes mellitus provided baseline spot urine samples. Urinary BPA concentrations (median value, 1.3 ng/mL) were low. Per-SD (4.56 ng/mL) increases in urinary BPA concentration were associated with incident CAD in age-, sex-, and urinary creatinine-adjusted models (n=1919; odds ratio=1.13; 95% confidence interval, 1.02-1.24; P=0.017). With CAD risk factor adjustment (including education, occupational social class, body mass index category, systolic blood pressure, lipid concentrations, and exercise), the estimate was similar but narrowly missed 2-sided significance (n=1744; odds ratio=1.11; 95% confidence interval, 1.00-1.23; P=0.058). Sensitivity analyses with the fully adjusted model, excluding those with early CAD (<3-year follow-up), body mass index >30, or abnormal renal function or with additional adjustment for vitamin C, C-reactive protein, or alcohol consumption, all produced similar estimates, and all showed associations at P≤0.05. Associations between higher BPA exposure (reflected in higher urinary concentrations) and incident CAD during >10 years of follow-up showed trends similar to previously reported cross-sectional findings in the more highly exposed NHANES respondents. Further work is needed to accurately estimate the prospective exposure-response curve and to establish the underlying mechanisms.

Effects of feeding polyphenol-rich winery wastes on digestibility, nitrogen utilization, ruminal fermentation, antioxidant status and oxidative stress in wethers.

PubMed

Ishida, Kyohei; Kishi, Yosuke; Oishi, Kazato; Hirooka, Hiroyuki; Kumagai, Hajime

2015-03-01

Four wethers were used in a 4 × 4 Latin square design experiment to evaluate the availability of two types of winery wastes, winery sediment and grape pomace, as ruminant feeds possessing antioxidant activities. Each wether was assigned to one of the following four treatments: (i) 75 g/kg winery sediment (WS) on a dry matter (DM) basis; (ii) 166 g/kg DM winery grape pomace (WP); (iii) control diet (CD; 17 g/kg DM soybean meal);and (iv) only tall fescue hay (TFH; no additive). Winery sediment and grape pomace had high levels of polyphenols and of radical scavenging activities. Feeding with winery sediment and grape pomace did not negatively affect the intake, but it depressed crude protein (CP) digestibility compared with CD (P = 0.052 and P < 0.01 for WS and WP, respectively). Polyphenols in winery wastes decreased ruminal ammonia production (P = 0.089 and P < 0.05), likely due to their inhibitive effect on microbial activities in the rumen. The addition of winery sediment and grape pomace decreased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG; an index of oxidative damages) excretion per day (P < 0.05 and P = 0.059). The results indicated that winery sediment and grape pomace could alter nitrogen metabolism and/or act as new antioxidants for ruminants. © 2014 Japanese Society of Animal Science.

Urinary fluoride as a monitoring tool for assessing successful intervention in the provision of safe drinking water supply in five fluoride-affected villages in Dhar district, Madhya Pradesh, India.

PubMed

Srikanth, R; Gautam, Anil; Jaiswal, Suresh Chandra; Singh, Pavitra

2013-03-01

Endemic fluorosis was detected in 31 villages in the Dhar district of Madhya Pradesh, Central India. Out of the 109 drinking water sources that were analyzed, about 67 % were found to contain high concentration of fluoride above the permissible level of 1.0 mg/l. Dental fluorosis among the primary school children in the age between 8 and 15 served as primary indicator for fluoride intoxication among the children. Urinary fluoride levels among the adults were found to be correlated with drinking water fluoride in 10 villages affected by fluoride. Intervention in the form of alternate safe water supply in five villages showed significant reduction in the urinary fluoride concentration when compared to the control village. Urinary fluoride serves as an excellent marker for assessing the effectiveness of intervention program in the fluoride-affected villages.

Differences in DNA-damage in non-smoking men and women exposed to environmental tobacco smoke (ETS).

PubMed

Collier, Abby C; Dandge, Sachin D; Woodrow, James E; Pritsos, Chris A

2005-07-28

There is much data implicating environmental tobacco smoke (ETS) in the development and progression of disease, notably cancer, yet the mechanisms for this remain unclear. As ETS is both a pro-oxidant stressor and carcinogen, we investigated the relationship of ETS exposure to intracellular and serum levels of DNA-damage, both oxidative 8-hydroxy-2-deoxyguanosine (8OHdG) and general, in non-smokers from non-smoking households, occupationally exposed to ETS. General DNA-damage consisting of single and double strand breaks, alkali-labile sites and incomplete base-excision repair, increased significantly in a dose-dependent manner with ETS exposure in men (P=0.015, n=32, Pearson) but not women (P=0.736, n=17). Intracellular 8OHdG-DNA-damage and general DNA-damage were both greater in men than women (P=0.0005 and 0.016, respectively) but 8OHdG serum levels did not differ between the genders. Neither 8OHdG-DNA-damage nor serum levels correlated with increasing ETS exposure. This is the first study to demonstrate dose-dependent increases in DNA-damage from workplace ETS exposure. Perhaps most interesting was that despite equivalent ETS exposure, significantly greater DNA-damage occurred in men than women. These data may begin to provide a mechanistic rationale for the generally higher incidence of some diseases in males due to tobacco smoke and/or other genotoxic stressors.

Population Pharmacokinetic-Pharmacodynamic Model of Oral Fludrocortisone and Intravenous Hydrocortisone in Healthy Volunteers.

PubMed

Hamitouche, Noureddine; Comets, Emmanuelle; Ribot, Mégane; Alvarez, Jean-Claude; Bellissant, Eric; Laviolle, Bruno

2017-05-01

This study aimed at describing the pharmacokinetics and the concentration-effect relationships of fludrocortisone and hydrocortisone on urinary sodium/potassium excretion in healthy volunteers. This was a placebo-controlled, randomized, double blind, crossover study, of oral fludrocortisone and intravenous hydrocortisone, given alone or in combination, in 12 healthy male volunteers. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics and pharmacokinetic-pharmacodynamic relationships on urinary sodium/potassium ratio for each drug. A one-compartment model was used to describe fludrocortisone and hydrocortisone pharmacokinetics. Mean plasma half-life was 1.40 h (95%CI [0.80;2.10]) for fludrocortisone and 2.10 h (95%CI [1.78;2.40]) for hydrocortisone. Clearance was 40.8 L/h (95%CI [33.6;48]) for fludrocortisone and 30 L/h (95%CI [25.3;34.7]) for hydrocortisone. An indirect response model was used to describe effects on urinary sodium/potassium ratio. Fludrocortisone plasma concentrations showed a wider inter-individual dispersion than hydrocortisone plasma concentrations. Urinary sodium/potassium ratio variability was also higher with fludrocortisone as compared to hydrocortisone. The plasma concentration of drug producing 50% of maximal inhibition of urinary sodium/potassium (IC 50 ) was about 200 times lower for fludrocortisone (0.08 μg/L, 95%CI [0.035;0.125]) than for hydrocortisone (16.7 μg/L, 95%CI [10.5;22.9]). Simulations showed that a 4-time per day administration regimen allow to achieve steady fludrocortisone plasma concentrations with stable decrease in urinary sodium/potassium ratio after the second administration of fludrocortisone. Fludrocortisone and hydrocortisone have short and similar plasma elimination half-lives in healthy subjects. Fludrocortisone plasma concentrations and effect on urinary sodium/potassium ratio had a higher inter-individual variability as compared to hydrocortisone. The administration regimen of fludrocortisone should be reconsidered.

8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine concentrations in various human body fluids: implications for their measurement and interpretation.

PubMed

Hu, Chiung-Wen; Cooke, Marcus S; Tsai, Yi-Hung; Chao, Mu-Rong

2015-02-01

8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most investigated product of oxidatively damaged DNA lesion that has been associated with the development of aging, cancer and some degenerative diseases. Here, we present the first liquid chromatography-tandem mass spectrometry method that enables the simultaneous measurement of its repair products in plasma and saliva, namely 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxodGuo. Using this method, we investigated the underlying transport mechanism of the repair products of oxidatively damaged DNA between cellular compartments and biological matrices. Plasma, saliva and urine samples were collected concurrently from 57 healthy subjects. Various deproteinization methods were evaluated, and the precipitants acetonitrile and sodium hydroxide-methanol were, respectively, selected for plasma and saliva samples due to their effect on recovery efficiencies and chromatography. The mean baseline concentrations of 8-oxoGua and 8-oxodGuo in plasma were demonstrated to be 0.21 and 0.016 ng/mL, respectively, while in saliva they were 0.85 and 0.010 ng/mL, respectively. A relatively high concentration of 8-oxoGua was found in saliva with a concentration factor (CF, concentration ratio of saliva to plasma) of 4 as compared to that of 8-oxodGuo (CF: 0.6), implying that 8-oxoGua in plasma may be actively transported to saliva, whereas 8-oxodGuo was most dependent on a passive diffusion. Good correlations between urine and plasma concentrations were observed for 8-oxoGua and 8-oxodGuo, suggesting that blood was a suitable matrix in addition to urine. Significant correlation between 8-oxoGua and 8-oxodGuo in urine was only observed when the concentrations were not corrected for urinary creatinine, raising the issue of applicability of urinary creatinine to adjust 8-oxoGua concentrations.

Effect of Chronic Administration of Forskolin on Glycemia and Oxidative Stress in Rats with and without Experimental Diabetes

PubMed Central

Ríos-Silva, Mónica; Trujillo, Xóchitl; Trujillo-Hernández, Benjamín; Sánchez-Pastor, Enrique; Urzúa, Zorayda; Mancilla, Evelyn; Huerta, Miguel

2014-01-01

Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8‑OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant. PMID:24688307

Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes.

PubMed

Ríos-Silva, Mónica; Trujillo, Xóchitl; Trujillo-Hernández, Benjamín; Sánchez-Pastor, Enrique; Urzúa, Zorayda; Mancilla, Evelyn; Huerta, Miguel

2014-01-01

Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8‑OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant.

Pseudoephedrine and preexercise feeding: influence on performance.

PubMed

Pritchard-Peschek, Kellie R; Osborne, Mark A; Slater, Gary J; Taaffe, Dennis R; Jenkins, David G

2013-06-01

This study examined the influence of preexercise food intake on plasma pseudoephedrine (PSE) concentrations and subsequent high-intensity exercise. In addition, urinary PSE concentrations were measured under the same conditions and compared with the present threshold of the World Anti-Doping Agency (WADA). Ten highly trained male cyclists and triathletes (age = 30.6 ± 6.6 yr, body mass [BM] = 72.9 ± 5.1 kg, and V˙O2max = 64.8 ± 4.5 mL·kg·min; mean ± SD) undertook four cycling time trials (TT), each requiring the completion of a set amount of work (7 kJ·kg BM) in the shortest possible time. Participants were randomized into a fed or nonfed condition and orally ingested 2.8 mg·kg BM of PSE or a placebo (PLA) 90 min before exercise; in the fed trials, they consumed a meal providing 1.5 g·kg BM of CHO. Venous blood was sampled at 30, 50, and 70 min and pre-warm-up and postexercise for the analysis of plasma PSE and catecholamine concentrations, and urine was also collected for the analysis of PSE concentration. Independent of the preexercise meal, 2.8 mg·kg BM of PSE did not significantly improve cycling TT performance. The fed trials resulted in lower plasma PSE concentrations at all time points compared with the nonfed trials. Both plasma epinephrine and blood lactate concentrations were higher in the PSE compared with the PLA trials, and preexercise and postexercise urinary PSE concentrations were significantly higher than the threshold (150 μg·mL) used by WADA to determine illicit PSE use. Irrespective of the preexercise meal, cycling TT performance of approximately 30 min was not improved after PSE supplementation. Furthermore, 2.8 mg·kg BM of PSE taken 90 min before exercise, with or without food, resulted in urinary PSE concentrations exceeding the present WADA threshold.

Phthalate metabolites in Norwegian mothers and children: Levels, diurnal variation and use of personal care products.

PubMed

Sakhi, Amrit Kaur; Sabaredzovic, Azemira; Cequier, Enrique; Thomsen, Cathrine

2017-12-01

Exposure to phthalates has been associated with reproductive and developmental toxicity. Data on levels of these compounds in the Norwegian population is limited. In this study, urine samples were collected from 48 mothers and their children in two counties in Norway. Eleven different phthalate metabolites originating from six commonly used phthalates in consumer products were determined. Concentrations of phthalate metabolites were significantly higher in children compared to mothers except for mono-ethyl phthalate (MEP). The mothers provided several urine samples during 24hours (h) and diurnal variation showed that the concentrations in the morning urine samples (24-8h) were significantly higher than at other time-periods for most of the phthalate metabolites. Intraclass correlation coefficients (ICCs) for 24-hour time-period were in the range of 0.49-0.81. These moderate to high ICCs indicate that one spot urine sample can be used to estimate the exposure to phthalates. Since a significant effect of time of day was observed, it is still advisable to standardize the collection time point to reduce the variation. For the mothers, the use of personal care products (PCPs) were less associated with morning urine samples than early day (8-12h) and evening (16-24h) urine samples. The use of perfume and hair products were positively associated with the urinary concentrations of low molecular weight phthalates. Use of shower soap and shampoo were positively associated with urinary concentration of di(2-ethylhexyl) phthalate (DEHP) metabolites. For children, face cream use was positively associated with phthalate metabolites in the morning samples, and hand soap use was negatively associated with concentration of urinary DEHP metabolites in afternoon/evening samples. Since different PCPs were associated with the urinary phthalate metabolites in different time-periods during a day, more than one spot urine sample might be required to study associations between urinary phthalate metabolites and the use of PCPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization.

PubMed

Carignan, Courtney C; Mínguez-Alarcón, Lidia; Williams, Paige L; Meeker, John D; Stapleton, Heather M; Butt, Craig M; Toth, Thomas L; Ford, Jennifer B; Hauser, Russ

2018-02-01

Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06). Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Different values of urinary fractionated metanephrines after unilateral adrenalectomy for pheochromocytoma according to time intervals after surgery.

PubMed

Cho, Yoon Y; Kim, Young N; Kim, Jung-Han; Jeong, Byong C; Lee, Soo-Youn; Kim, Jae H

2017-01-01

Background After adrenalectomy, urinary fractionated metanephrine concentrations are expected to be reduced. However, there are few studies suggesting cut-offs for adrenalectomy patients. Methods Urinary metanephrine and normetanephrine concentrations in adrenalectomy patients and two controls were compared and hormonal concentrations were evaluated via time intervals after surgery. Results The median urinary metanephrine level after unilateral adrenalectomy was lower than that of the non-pheochromocytoma controls but comparable to healthy controls. Urinary normetanephrine concentrations did not differ between adrenalectomy patients and non-pheochromocytoma controls, although both group had levels higher than those of healthy controls. The median urinary normetanephrine level in the immediate postoperative period was higher than in the later period. Conclusions Urinary metanephrine concentrations were lower after adrenalectomy, but urinary normetanephrine concentrations were not changed compared with the non-pheochromocytoma controls. However, urinary normetanephrine concentrations in the patient group were higher than levels in the heathy controls.

Influence of body mass index status on urinary creatinine and specific gravity for epidemiological study of children.

PubMed

Wang, Bin; Tang, Chuanxi; Wang, Hexing; Zhou, Wei; Chen, Yue; Zhou, Ying; Jiang, Qingwu

2015-11-01

In epidemiological studies, urinary biomonitoring is a valid approach to assess the association between environmental chemical exposure and children's health. Many clinical biomarkers (e.g., endogenous metabolites) are also based on analysis of urine. Considering the variability in urinary output, urinary concentrations of chemicals are commonly adjusted by creatinine and specific gravity (SG). However, there is a lack of systematic evaluation of their appropriateness for children. Furthermore, urinary SG and creatinine excretion could be influenced by body mass index (BMI), but the effect of BMI status on the two correction factors is unknown. We measured SG and creatinine concentrations of repeated first morning urine samples collected from 243 primary school children (8-11 years) over 5 consecutive weekdays. Urinary SG presented a higher temporal consistency compared with creatinine. Urinary SG was associated with sex (p < 0.001), whereas sex (p =0.034) and BMI (p = 00.008) were associated with urinary creatinine levels. Inter-day collection time was not associated with SG or creatinine after excluding the effect of Monday as a confounder. When stratified by BMI status, none of the factors were associated with creatinine among the overweight and obese children. Generally, SG is preferable for correcting the variability in urinary output for children although creatinine correction may also perform well in overweight and obese children. SG correction is recommended for epidemiological exposure analysis in children based on urinary levels of exogenous or endogenous metabolites.

Occupational exposure of cashiers to Bisphenol A via thermal paper: urinary biomonitoring study.

PubMed

Ndaw, Sophie; Remy, Aurélie; Jargot, Danièle; Robert, Alain

2016-08-01

As an essential component of polycarbonate plastics and epoxy resins, Bisphenol A (BPA) is found in numerous industrial and consumer products. BPA may cause adverse health effects because of its endocrine activity. General population exposure to this compound mainly through diet is well documented. Thermal paper was also identified as a source of BPA through dermal intake. In this study, we investigated whether frequent contact with thermal paper is associated with an increase in urinary BPA excretion. We evaluated the exposure to BPA in cashiers and in non-occupationally exposed workers from several workplaces. Urinary BPA was quantified in free (unconjugated) and total (unconjugated plus conjugated) forms in 24-h and spot urine samples using LC-MS/MS. BPA concentration in thermal paper was also measured from each workplace. In addition, participants provided information on job, food and drink, tobacco consumption and hands wash during the sampling period through a questionnaire. Urine samples were collected from 90 cashiers and 44 controls. Free and total BPA were detected in all samples. The median urinary total BPA concentration was 3.54 µg/L (2.89 µg/g creatinine) for controls and 8.92 µg/L (6.76 µg/g creatinine) for cashiers. For the free BPA, the median urinary concentration was 0.20 µg/L (0.21 µg/g creatinine) for controls and 0.28 µg/L (0.22 µg/g creatinine) for cashiers. Any correlation was found between the urinary concentration levels and the number of thermal receipts handled. Hand washes frequency, age, job length of service and tobacco consumption had also no effect on the BPA excretions. A significant increase in urinary total BPA concentration was observed for cashiers handling daily thermal paper receipts. However, no significant increase was observed in urinary free BPA concentration. These findings are particularly interesting for risk assessment since all available data on occupational exposure to BPA through thermal paper were obtained from models or from simulated experiments.

Urinary chromium concentrations in humans following ingestion of safe doses of hexavalent and trivalent chromium: Implications for biomonitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finley, B.L.; Scott, P.K.; Norton, R.L.

1996-08-09

This study evaluates the significance of increased urinary chromium concentrations as a marker of chromium exposure and potential health risk. Six human volunteers ingested trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)] at doses that are known to be safe but higher than typical levels. The following dosing regimen was used: d 1-7, 200 {mu}g/d chromium picolinate; d 8-10, Cr(VI) ingestion at the U.S. Environmental Protection Agency (EPA) reference dose (RfD) of 0.005 mg/kg/d; d 11-13, no dose; d 14-16, Cr(III) ingestion at the U.S. EPA RfD of 1.0 mg/kg/d; and 17-18, postdose. Findings are as follows: (1) ingestion of 200more » {mu}g/d of chromium picolinate yielded significantly elevated urine concentrations such that each participant routinely exceeded background, (2) ingestion of the Cr(VI) RfD (0.005 mg/kg/d) yielded individual mean urinary chromium levels (1.2-2.3 {mu}g/L) and a pooled mean urinary chromium level (2.4 {mu}g/L) that significantly exceeded background, and (3) ingestion of the Cr(III) RfD yielded no significantly exceeded background, and (3) ingestion of the Cr(III) RfD yielded no significant increase in urinary chromium concentrations, indicating that little, if any, absorption occurred. Our work identified three critical issues that need to be accounted for in any future studies that will use urinary chromium as a marker of exposure. First, a minimum urinary chromium concentration of approximately 2 {mu}g/L should be used as a screening level to critically identify individuals who may have experienced elevated exposures to chromium. Second, if Cr(III) levels in soils are known to be less than 80,000 ppm and the Cr(III) is insoluble, urinary chromium concentrations are not an appropriate marker of exposure. Third, newer forms of chromium supplements that contain organic forms of Cr(III) must be considered potential confounders and their contribution to residential chromium uptake must be carefully evaluated. 19 refs., 7 figs., 3 tabs.« less

Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with formula.

PubMed

Haschke-Becher, Elisabeth; Brunser, Oscar; Cruchet, Sylvia; Gotteland, Martin; Haschke, Ferdinand; Bachmann, Claude

2008-01-01

Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1). In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4-5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 x 10(8)/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis. Copyright 2008 S. Karger AG, Basel.

Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation.

PubMed

Park, Yune-Jung; Yoo, Seung-Ah; Kim, Ga-Ram; Cho, Chul-Soo; Kim, Wan-Uk

2016-10-12

Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis.

Dissociation between urinary pyrraline and pentosidine concentrations in diabetic patients with advanced nephropathy.

PubMed

Aso, Yoshimasa; Takanashi, Keishi; Sekine, Kyouichi; Yoshida, Noboru; Takebayashi, Kohzo; Yoshihara, Kazuhiro; Inukai, Toshihiko

2004-08-01

It has been reported that the concentrations of both pyrraline and pentosidine, well-characterized advanced glycation end products, are increased in the urine of diabetic patients. To determine factors that influence the urinary excretion of pyrraline or pentosidine, we compared pyrraline or pentosidine concentrations with glycemic-control indexes, urinary albumin excretion, and urinary beta2-microglobulin in patients with type 2 diabetes. The study was conducted in 39 age-matched healthy control subjects and 50 diabetic patients, including 22 patients with normoalbuminuria, 15 with microalbuminuria, and 13 with macroalbuminuria. Both urinary pyrraline and pentosidine were measured in early-morning urine specimens with the use of high-pressure liquid chromatography. The urinary pentosidine concentration was significantly higher in diabetic patients than in control subjects (P <.01). In contrast, the urinary pyrraline concentration was significantly lower in diabetic patients than in control subjects (P <.001). Urinary pentosidine concentrations were greater in diabetic patients with macroalbuminuria and microalbuminuria than in those with normoalbuminuria. However, urinary pyrraline concentrations were significantly lower in diabetic patients with advanced nephropathy. Both the hemoglobin A(1c) (HbA(1c)) and the preceding year's mean HbA(1c) were lower in patients with macroalbuminuria than in those with normoalbuminuria or microalbuminuria. Urinary pyrraline, but not pentosidine, showed a significantly positive correlation with the preceding year's mean HbA(1c) (P<0.01). Multivariate analysis disclosed that urinary beta-2-microglobulin was independently correlated with the urinary concentrations of pentosidine and pyrraline (P <.05 for both). We conclude that the urinary concentration of pentosidine is greater in diabetic patients with overt nephropathy, whereas the urinary pyrraline concentration is significantly lower in diabetic patients with overt nephropathy. Because urinary pyrraline is more directly influenced by glycemia than by pentosidine, the difference in glycemic control among diabetic patients with various grades of nephropathy may be responsible for a dissociation between urinary pyrraline and pentosidine concentrations in patients with overt diabetic nephropathy.

The efficacy of an antioxidant cocktail on lipid peroxide level and superoxide dismutase activity in aged rat brain and DNA damage in iron-induced epileptogenic foci.

PubMed

Komatsu, M; Hiramatsu, M

2000-08-07

Mixed natural antioxidants can be combined in a prophylactic food against age related disease involving reactive oxygen species. beta-Catechin is an antioxidant drink, having free radical scavenging activities. It contains green tea extract as a main component as well as ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E. In the present study, we examined the effect of beta-catechin on lipid peroxide formation and superoxide dismutase (SOD) activity in aged rat brain and the effect on 8-hydroxy-2'-deoxyguanosine (8-OHdG) in ipsilateral cortex, 30 min after ferric chloride solution was injected into the left cortex of rats. beta-Catechin solution was orally administered to aged rats and normal rats for 1 month. One-month administration of beta-catechin solution increased SOD activity in the mitochondria fraction of striatum and midbrain and decreased thiobarbiturate reactive substance formation in the cortex and cerebellum of aged rats. It also inhibited 8-OHdG formation in the ipsilateral cortex 30 min after injection of ferric chloride solution. These results suggest that beta-catechin is a suitable prophylactic beverage against age-related neurological diseases associated with reactive oxygen species.

6-gingerol prevents patulin-induced genotoxicity in HepG2 cells.

PubMed

Yang, Guang; Zhong, Laifu; Jiang, Liping; Geng, Chengyan; Cao, Jun; Sun, Xiance; Liu, Xiaofang; Chen, Min; Ma, Yufang

2011-10-01

Patulin (PAT) is a mycotoxin produced by several Penicillium, Aspergillus and Byssochlamys species. Since PAT is a potent genotoxic compound, and PAT contamination is common in fruits and fruit products, the search for newer, better agents for protection against genotoxicity of PAT is required. In this study, the chemoprotective effect of 6-gingerol against PAT-induced genotoxicity in HepG2 cells was investigated. The comet assay and micronucleus test (MNT) were used to monitor genotoxic effects. To further elucidate the underlying mechanisms, the intracellular generation of reactive oxygen species (ROS) and level of reduced glutathione (GSH) were tested. In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG). The results showed that 6-gingerol significantly reduced the DNA strand breaks and micronuclei formation caused by PAT. Moreover, 6-gingerol effectively suppressed PAT-induced intracellular ROS formation and 8-OHdG level. The GSH depletion induced by PAT in HepG2 cells was also attenuated by 6-gingerol pretreatment. These findings suggest that 6-gingerol has a strong protective ability against the genotoxicity caused by PAT, and the antioxidant activity of 6-gingerol may play an important part in attenuating the genotoxicity of PAT. Copyright © 2011 John Wiley & Sons, Ltd.

Exposure to Bisphenol A and Other Phenols in Neonatal Intensive Care Unit Premature Infants

PubMed Central

Calafat, Antonia M.; Weuve, Jennifer; Ye, Xiaoyun; Jia, Lily T.; Hu, Howard; Ringer, Steven; Huttner, Ken; Hauser, Russ

2009-01-01

Objective We previously demonstrated that exposure to polyvinyl chloride plastic medical devices containing di(2-ethylhexyl) phthalate (DEHP) was associated with higher urinary concentrations of several DEHP metabolites in 54 premature infants in two neonatal intensive care units than in the general population. For 42 of these infants, we evaluated urinary concentrations of several phenols, including bisphenol A (BPA), in association with the use of the same medical devices. Measurements We measured the urinary concentrations of free and total (free plus conjugated) species of BPA, triclosan, benzophenone-3, methyl paraben, and propyl paraben. Results The percentage of BPA present as its conjugated species was > 90% in more than three-quarters of the premature infants. Intensity of use of products containing DEHP was strongly associated with BPA total concentrations but not with any other phenol. Adjusting for institution and sex, BPA total concentrations among infants in the group of high use of DEHP-containing products were 8.75 times as high as among infants in the low use group (p < 0.0001). Similarly, after adjusting for sex and DEHP-containing product use category, BPA total concentrations among infants in Institution A were 16.6 times as high as those among infants in Institution B (p < 0.0001). Conclusion BPA geometric mean urinary concentration (30.3 μg/L) among premature infants undergoing intensive therapeutic medical interventions was one order of magnitude higher than that among the general population. Conjugated species were the primary urinary metabolites of BPA, suggesting that premature infants have some capacity to metabolize BPA. The differences in exposure to BPA by intensity of use of DEHP-containing medical products highlight the need for further studies to determine the specific source(s) of exposure to BPA. PMID:19440505

Pseudonephritis is associated with high urinary osmolality and high specific gravity in adolescent soccer players.

PubMed

Van Biervliet, Stephanie; Van Biervliet, Jean Pierre; Watteyne, Karel; Langlois, Michel; Bernard, Dirk; Vande Walle, Johan

2013-08-01

The study aimed to evaluate the effect of exercise on urine sediment in adolescent soccer players. In 25 15-year-old (range 14.4-15.8 yrs) athletes, urinary protein, osmolality and cytology were analyzed by flow cytometry and automated dipstick analysis before (T(0)), during (T(1)), and after a match (T(2)). All athletes had normal urine analysis and blood pressure at rest, tested before the start of the soccer season. Fifty-eight samples were collected (T(0): 20, T(1): 17, T(2): 21). Proteinuria was present in 20 of 38 samples collected after exercise. Proteinuria was associated with increased urinary osmolality (p < .001) and specific gravity (p < .001). Hyaline and granular casts were present in respectively 8 of 38 and 8 of 38 of the urinary samples after exercise. The presence of casts was associated with urine protein concentration, osmolality, and specific gravity. This was also the case for hematuria (25 of 38) and leucocyturia (9 of 38). Squamous epithelial cells were excreted in equal amounts to white and red blood cells. A notable proportion of adolescent athletes developed sediment abnormalities, which were associated with urinary osmolality and specific gravity.

Plasma and Urinary Aluminum Concentrations in Severely Anemic Geophagous Pregnant Women in the Bas Maroni Region of French Guiana: A Case-Control Study

PubMed Central

Lambert, Veronique; Boukhari, Rachida; Nacher, Mathieu; Goullé, Jean-Pierre; Roudier, Estelle; Elguindi, Wael; Laquerrière, Annie; Carles, Gabriel

2010-01-01

The clays consumed by geophagous individuals contain large quantities of aluminum, a known neurological and hematological toxin. This is the first study to evaluate the risk of aluminum poisoning in geophagous individuals. Blind determinations of plasma and urinary aluminum concentrations were carried out in 98 anemic geophagous pregnant women and 85 non-anemic non-geophagous pregnant women. Aluminum concentrations were significantly higher (P < 0.0001) in the geophagous anemic women than in the controls, with odds ratios of 6.83 (95% confidence interval [CI] = 2.72–19.31) for plasma concentrations (13.92 ± 14.09 μg/L versus 4.95 ± 7.11 μg/L) and 5.44 (95% CI = 2.17–14.8) for urinary concentrations (92.83 ± 251.21 μg/L versus 12.11 ± 23 μg/L). The ingested clay is the most likely source of this overexposure to aluminum. If confirmed, the clinical consequences of this absorption for pregnant women and their offspring should be explored. PMID:21036845

[Weight maintenance in humans. Could it mimic calorie restriction of animal models?].

PubMed

de la Maza, M Pía C; Vivien, Z Gattás; Zavala, Aquiles R; Cataldo, Vicente D; Guerra, Julio S; Gladys, A Barrera; Laura, B Leiva; Sandra, B Hirsch; Daniel, B Bunout

2004-10-01

Energy restriction (ER) extends life span in animals, by decreasing oxidative stress. To compare adiposity, metabolic variables and DNA oxidative damage, among adults, reporting a constant body weight (weight maintainers), versus those reporting a progressive increase (weight gainers). Clinical history, dietary recall, anthropometric measures, abdominal CT scan and fasting blood samples (to measure lipoproteins, glucose and insulin), were obtained in 44 males. These subjects were classified as weight maintainers if they had a change in weight of 3 kg or less in the last 10 years, or weight gainers, if they had a weight increment of more than 6 kg, in the same lapse. Oxidative damage was assessed by 8-hydroxydeoxyguanosine (8-OHdG), in DNA extracted from circulating lymphocytes, in 5 weight maintainers, 8 weight gainers and 5 healthy elders. Energy Intake was 18% higher in weight gainers (p <0.01). Adiposity and central fat were higher among weight gainers (p <0.01). Abdominal fat correlated with serum lipoproteins, glucose and insulin sensitivity, assessed by the Homeostasis Model Assessment (HOMA). 8-OHdG levels did not differ between groups. The analysis of weight change based on the clinical history correlates with actual body composition, thus it may be a reliable indicator of long term energy Intake. This method could be comparable to weight clamp models employed in animals to study aging.

Norfloxacin penetration into human renal and prostatic tissues.

PubMed Central

Bergeron, M G; Thabet, M; Roy, R; Lessard, C; Foucault, P

1985-01-01

Concurrent norfloxacin concentrations in serum, kidney, and prostatic tissue were determined in 14 patients. Mean ratios of norfloxacin concentration in tissue over concentration in serum were 6.6 +/- 2.8 for the kidney and 1.7 +/- 0.2 for the prostate samples. The levels were above the MICs of most urinary pathogens. PMID:3834837

Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women.

PubMed

Takechi, Ryusuke; Alfonso, Helman; Hiramatsu, Naoko; Ishisaka, Akari; Tanaka, Akira; Tan, La'Belle; Lee, Andy H

2016-03-01

This study investigated green tea catechins in plasma and urine and chronic disease biomarkers. We hypothesized that plasma and urinary concentration of green tea catechins are associated with cardiovascular disease and diabetes biomarkers. First void urine and fasting plasma samples were collected from 57 generally healthy females aged 38 to 73 years (mean, 52 ± 8 years) recruited in Himeji, Japan. The concentrations of plasma and urinary green tea catechins were determined by liquid chromatography coupled with mass tandem spectrometer. Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, insulin, glycated hemoglobin, and C-reactive protein in plasma/serum samples were analyzed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman correlation coefficients. The results showed weak associations between plasma total catechin and triglyceride (r = -0.30) and LDL cholesterol (r = -0.28), whereas plasma (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate, and (-)-epicatechin exhibited weak to moderate associations with triglyceride or LDL cholesterol, but little associations with HDL cholesterol, body fat, and body mass index were evident. Urinary total catechin was weakly associated with triglyceride (r = -0.19) and LDL cholesterol (r = -0.15), whereas urinary (-)-epigallocatechin-3-gallate (r = -0.33), (-)-epigallocatechin (r = -0.23), and (-)-epicatechin-3-gallate (r = -0.33) had weak to moderate correlations with triglyceride and similarly with body fat and body mass index. Both plasma (r = -0.24) and urinary (r = -0.24) total catechin, as well as individual catechins, were weakly associated with glycated hemoglobin. Plasma total and individual catechins were weakly to moderately associated with C-reactive protein, but not the case for urinary catechins. In conclusion, we found weak to moderate associations between plasma and urinary green tea catechin concentrations and plasma biomarkers of cardiovascular disease and diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Persistent konzo and cyanogen toxicity from cassava in northern Mozambique.

PubMed

Ernesto, Mario; Cardoso, A Paula; Nicala, Domingos; Mirione, Estevão; Massaza, Fernando; Cliff, Julie; Haque, M Rezaul; Bradbury, J Howard

2002-06-01

We aimed to detect new cases of konzo and monitor cyanogen exposure from cassava flour in communities previously affected by konzo epidemics in Nampula Province, northern Mozambique. Other objectives were to detect subclinical upper motor neuron damage in schoolchildren and test a new kit to measure urinary thiocyanate concentration. In 1999 and 2000, we carried out active and passive case detection for konzo in Memba and Mogincual Districts. In July and October, 1999, we collected cassava flour from 30 houses in three communities and measured cyanogen concentrations with a picrate kit. In October 1999, we examined all schoolchildren in three communities for ankle clonus and measured urinary thiocyanate concentration in thirty schoolchildren in each of five communities with a picrate kit. We found 27 new cases of konzo in Mogincual District. Mean total cyanogen concentrations in cassava flour varied between both seasons and years, but were always high, ranging from 26 to 186 ppm. Very high mean levels at three sites in November 1998 and July 1999 were probably due to low rainfall in the 1997-1998 season. The proportion of schoolchildren with ankle clonus varied from 8 to 17%. The new picrate kit for urinary thiocyanate worked well; mean concentrations in schoolchildren ranged from 225 to 384 micromol x l(-1). Konzo and sub-clinical upper motor neuron damage persist in poor rural communities in northern Mozambique, associated with high cyanogen concentrations in cassava flour and high urinary thiocyanate concentrations in schoolchildren.

Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

PubMed

Bellés, Montserrat; Gonzalo, Sergio; Serra, Noemí; Esplugas, Roser; Arenas, Meritxell; Domingo, José Luis; Linares, Victoria

2017-07-01

Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium ( 137 Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137 Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation ( 137 Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137 Cs). Further investigations are required to clarify the mechanisms involved in the internal IR-induced nephrotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of cadmium on forage kale (Brassica oleracea var. viridis cv "Prover") after 3-,10- and 56-day exposure to a Cd-spiked field soil.

PubMed

Bernard, Fabien; Dumez, Sylvain; Lemière, Sébastien; Platel, Anne; Nesslany, Fabrice; Deram, Annabelle; Vandenbulcke, Franck; Cuny, Damien

2018-03-15

Cadmium (Cd) is a highly toxic element for living organisms and is widespread in metal-contaminated soils. As organisms which can grow up on these polluted areas, plants have some protection mechanisms against Cd issues. Among the plant kingdom, the Brassicaceae family includes species which are known to be able to tolerate and accumulate Cd in their tissues. In this study, Brassica oleracea var. viridis cv "Prover" was exposed to a range of artificially Cd-contaminated soils (from 2.5 up to 20 mg kg -1 ) during 3, 10, and 56 days and the effects on life traits, photosynthesis activity, antioxidant enzymatic activities were studied. Metal accumulation was quantified, as well as DNA damage, by means of the comet assay and immunodetection of 8-OHdG levels. Globally, B. oleracea was relatively tolerant to those Cd exposures. However, comet assay and detection of 8-OHdG revealed some DNA damage but which are not significant. According to metal accumulation analysis, B. oleracea var. viridis cv Prover could be a good candidate for alternative growing in contaminated areas.

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

PubMed Central

Arruda, Jose A. L.; Nascimento, Luiz; Mehta, Pradeep K.; Rademacher, Donald R.; Sehy, John T.; Westenfelder, Christof; Kurtzman, Neil A.

1977-01-01

Measurement of urine to blood (U-B) carbon dioxide tension (PCO2) gradient during alkalinization of the urine has been suggested to assess distal H+ secretion. A fact that has not been considered in previous studies dealing with urinary PCO2 is that dissolution of HCO3 in water results in elevation of PCO2 which is directly proportional to the HCO3 concentration. To investigate the interrelationship of urinary HCO3 and urinary acidification, we measured U-B PCO2 in (a) the presence of enhanced H+ secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H+ secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H+ secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO3 levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO3 concentration and U-B PCO2. At similar plasma HCO3 levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally. At a very high plasma HCO3 (>50 meq/liter), BB rats raised urine pH, urine HCO3 concentration, and U-B PCO2 to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO3, and U-B PCO2 normally at moderately elevated plasma HCO3 levels; at very high plasma HCO3 levels, CRF rats achieved a highly alkaline urine but failed to raise U-B PCO2. Dogs and patients with CRF were also unable to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally at moderately elevated plasma HCO3 levels. In rats, dogs, and man, U-B PCO2 was directly related to urine HCO3 concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO3 levels, animals with a distal acidification defect failed to raise U-B PCO2; increasing the plasma HCO3 to very high levels resulted in a significant increase in urine HCO3 concentration and U-B PCO2. The observed urinary PCO2 was very close to the PCO2 which would be expected by simple dissolution of a comparable amount of HCO3 in water. These data demonstrate that, in highly alkaline urine, urinary PCO2 is largely determined by concentration of urinary HCO3 and cannot be used as solely indicating distal H+ secretion. PMID:893680

Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity.

PubMed

Tran, V; Tindula, G; Huen, K; Bradman, A; Harley, K; Kogut, K; Calafat, A M; Nguyen, B; Parra, K; Ye, X; Eskenazi, B; Holland, N

2017-04-01

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

Prenatal Phthalate Exposure and 8-Isoprostane among Mexican-American Children with High Prevalence of Obesity

PubMed Central

Tran, Vy; Tindula, Gwen; Huen, Karen; Bradman, Asa; Harley, Kim; Kogut, Katherine; Calafat, Antonia M.; Nguyen, Brian; Parra, Kimberly; Ye, Xiaoyun; Eskenazi, Brenda; Holland, Nina

2016-01-01

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species (ROS) and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5-, 9- and 14-years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year old children. No associations were observed between 8-isoprostane and BMI, BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks gestation [monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates] were negatively associated with 8-isoprostane concentrations among 9 year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates. PMID:28031075

Weight increase and overweight are associated with DNA oxidative damage in skeletal muscle.

PubMed

de la Maza, María-Pía; Olivares, Daniela; Hirsch, Sandra; Sierralta, Walter; Gattás, Vivien; Barrera, Gladys; Bunout, Daniel; Leiva, Laura; Fernández, Mireya

2006-12-01

Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance. During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported <4kg increase, and weight gainers (WG) reported >5kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-alpha, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66-101yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-alpha and IL-6) were obtained. 8OHdG was higher in WG compared with WM (149.1+/-16.2 versus 117.8+/-29.5, P=0.03), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9+/-7.6 versus 9.8+/-6.3) but noticeably higher in elderly subjects (21.5+/-15.3, P=0.059). TNF-alpha protein in WG was higher compared with WM (114.0+/-41.7 versus 70.1+/-23.3, P=0.025), and was associated with weight increase. Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation.

DNA catabolites in triathletes: effects of supplementation with an aronia-citrus juice (polyphenols-rich juice).

PubMed

García-Flores, Libia Alejandra; Medina, Sonia; Cejuela-Anta, Roberto; Martínez-Sanz, José Miguel; Abellán, Ángel; Genieser, Hans-Gottfried; Ferreres, Federico; Gil-Izquierdo, Ángel

2016-04-01

In this study we analyzed whether our aronia-citrus juice (ACJ, the composition is based on a mixture of 95% citrus juice with 5% of Aronia melanocarpa juice), rich in polyphenols, and physical exercise had an effect on seven catabolites of DNA identified in plasma and on a urine isoprostane (8-iso-PGF2α). Sixteen elite triathletes on a controlled diet for triathlon training (45 days) were used in this clinical trial. Our results show a decrease in the 8-hydroxy-2'-deoxyguanosine concentration due to chronic physical exercise. The ACJ intake and physical exercise maintained the guanosine-3',5'-cyclic monophosphate plasmatic concentrations and decreased the concentration of 8-hydroxyguanine as well as urinary values of 8-iso-PGF2α. Finally, we observed a significant increase in the 8-nitroguanosine levels in triathletes after ACJ intake, compared to the placebo stage. It is concluded that the combination of the intake of ACJ, rich in polyphenolic compounds, with adequate training was able to influence the plasmatic and urinary values of oxidative stress biomarkers. This suggests a positive effect on the oxidative damage and potential associations with DNA repair mechanisms.

Febuxostat ameliorates diabetic renal injury in a streptozotocin-induced diabetic rat model.

PubMed

Lee, Hong-Joo; Jeong, Kyung Hwan; Kim, Yang Gyun; Moon, Joo Young; Lee, Sang Ho; Ihm, Chun Gyoo; Sung, Ji Youn; Lee, Tae Won

2014-01-01

Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the inflammatory and oxidative effects of diabetes-induced renal damage through inhibition of XO and XDH activities. © 2014 S. Karger AG, Basel.

Role of geraniol against lead acetate-mediated hepatic damage and their interaction with liver carboxylesterase activity in rats.

PubMed

Ozkaya, Ahmet; Sahin, Zafer; Kuzu, Muslum; Saglam, Yavuz Selim; Ozkaraca, Mustafa; Uckun, Mirac; Yologlu, Ertan; Comakli, Veysel; Demirdag, Ramazan; Yologlu, Semra

2018-02-01

In this study, the effect of geraniol (50 mg/kg for 30 d), a natural antioxidant and repellent/antifeedant monoterpene, in a rat model of lead acetate-induced (500 ppm for 30 d) liver damage was evaluated. Hepatic malondialdehyde increased in the lead acetate group. Reduced glutathione unchanged, but glutathione S-transferase, glutathione reductase, as well as carboxylesterase activities decreased in geraniol, lead acetate and geraniol + lead acetate groups. 8-OhDG immunoreactivity, mononuclear cell infiltrations and hepatic lead concentration were lower in the geraniol + lead acetate group than the lead acetate group. Serum aspartate aminotransferase and alanine aminotransferase activities increased in the Pb acetate group. In conclusion, lead acetate causes oxidative and toxic damage in the liver and this effect can reduce with geraniol treatment. However, we first observed that lead acetate, as well as geraniol, can affect liver carboxylesterase activity.

Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.

PubMed Central

Yager, J W; Hicks, J B; Fabianova, E

1997-01-01

Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic. Images Figure 1. A Figure 1. B Figure 2. PMID:9347899

Urinary concentrations of benzophenone-type ultra violet light filters and reproductive parameters in young men.

PubMed

Adoamnei, Evdochia; Mendiola, Jaime; Moñino-García, Miriam; Vela-Soria, Fernando; Iribarne-Durán, Luz M; Fernández, Mariana F; Olea, Nicolás; Jørgensen, Niels; Swan, Shanna H; Torres-Cantero, Alberto M

2018-04-01

Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals frequently added to personal care products, insect repellents, sunscreens, and beverage and food packaging to diminish the harmful effects of UV sunlight on human skin or foodstuffs. BP-type UV filters have shown negative effects on male reproduction function in in vitro and animal models, but human epidemiologic studies are limited. The goal of this study was to examine associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels. This is a cross-sectional study with 215 young university students (18-23 years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm counts, motility and morphology. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and estradiol (E2). Associations between urinary concentrations of BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders. Ninety-seven percent of the men had detectable urinary concentrations of at least one of the five BP-type UV filters quantified. After adjustment for important covariates (body mass index, smoking status and time of blood sample collection), there was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (β = 0.08, 95%CI: 0.009; 0.15 and β = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (β = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (β = -0.11, 95%CI: -0.21; -0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or between any semen parameters and any of the urinary BP-type UV filters quantified. Our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male populations. Copyright © 2018 Elsevier GmbH. All rights reserved.

High human exposure to cobalt and other metals in Katanga, a mining area of the Democratic Republic of Congo.

PubMed

Banza, Célestin Lubaba Nkulu; Nawrot, Tim S; Haufroid, Vincent; Decrée, Sophie; De Putter, Thierry; Smolders, Erik; Kabyla, Benjamin Ilunga; Luboya, Oscar Numbi; Ilunga, Augustin Ndala; Mutombo, Alain Mwanza; Nemery, Benoit

2009-08-01

The human health impact of the historic and current mining and processing of non-ferrous metals in the African Copperbelt is not known. This study assessed the exposure to metals in the population of Katanga, in the south east of the Democratic Republic of Congo, using biomonitoring. Seventeen metals (including Cd, Co, Cu, Pb, U) and non-metals (including As) were measured by ICP-MS in urine spot samples from 351 subjects (32% women), aged 2-74 yr (mean 33 yr). Forty subjects (controls) lived 400 km outside the mining area; 311 subjects lived in the mining area, either very close (< 3 km) (n=179; 6 communities) or moderately close (3-10 km) (n=132; 4 communities) to mines or smelting plants. For all metals (except Ni) urinary concentrations were significantly higher in subjects from the mining area than in control subjects. In subjects living very close to mines or smelting plants, the geometric means (25th-75th percentile) of urinary concentrations, expressed as microg/g creatinine, were 17.8 (10.9-29.0) for As, 0.75 (0.38-1.16) for Cd, 15.7 (5.27-43.2) for Co, 17.1 (8.44-43.2) for Cu, 3.17 (1.47-5.49) for Pb and 0.028 (0.013-0.065) for U, these values being significantly higher than those of subjects living 3-10 km from mines or industrial operations. Urinary Co concentrations were markedly elevated, exceeding 15 microg/g creatinine in 53% of the subjects, and even 87% of children (<14 yr), living very close to the mining areas. Urinary As was also high (79% above 10 microg/g creatinine in subjects living very close to the mining areas). Compared with background values from the US general population, subjects living very close to areas of mining or refining had 4-, 43-, 5- and 4-fold higher urinary concentrations of Cd, Co, Pb and U, respectively. This first biomonitoring study of metal exposure in the African Copperbelt reveals a substantial exposure to several metals, especially in children. The urinary Co concentrations found in this population are the highest ever reported for a general population. The pathways of exposure and health significance of these findings need to be further investigated.

Environmental Tobacco Smoke Exposure and Children’s Intelligence at 8–11 Years of Age

PubMed Central

Park, Subin; Cho, Soo-Churl; Hong, Yun-Chul; Shin, Min-Sup; Yoo, Hee Jeong; Han, Doug Hyun; Cheong, Jae Hoon

2014-01-01

Background: Evidence supporting a link between postnatal environmental tobacco smoke (ETS) exposure and cognitive problems among children is mounting, but inconsistent. Objectives: We examined the relationship between ETS exposure, measured using urine cotinine, and IQ scores in Korean school-aged children. Methods: The participants were 996 children 8–11 years of age recruited from five administrative regions in South Korea. We performed a cross-sectional analysis of urinary cotinine concentrations and IQ scores obtained using the abbreviated form of a Korean version of the Wechsler Intelligence Scales for Children. Associations were adjusted for potential confounders, and estimates were derived with and without adjustment for mother’s Full-Scale IQ (FSIQ) score. Results: After adjusting for sociodemographic and developmental covariates, urinary cotinine concentrations were inversely associated with FSIQ, Verbal IQ (VIQ), Performance IQ (PIQ), vocabulary, math, and block design scores. Following further adjustment for maternal IQ, only the VIQ scores remained significantly associated with urinary cotinine concentration (B = –0.31; 95% CI: –0.60, –0.03 for a 1-unit increase in natural log-transformed urine cotinine concentration; p = 0.03). Conclusion: Urine cotinine concentrations were inversely associated with children’s VIQ scores before and after adjusting for maternal IQ. Further prospective studies with serial measurements of cotinine are needed to confirm our findings. Citation: Park S, Cho SC, Hong YC, Kim JW, Shin MS, Yoo HJ, Han DH, Cheong JH, Kim BN. 2014. Environmental tobacco smoke exposure and children’s intelligence at 8–11 years of age. Environ Health Perspect 122:1123–1128; http://dx.doi.org/10.1289/ehp.1307088 PMID:24911003

Simultaneous Analysis of Seven Biomarkers of Oxidative Damage to Lipids, Proteins, and DNA in Urine.

PubMed

Martinez, Maria P; Kannan, Kurunthachalam

2018-06-05

The determination of oxidative stress biomarkers (OSBs) is useful for the assessment of health status and progress of diseases in humans. Whereas previous methods for the determination of OSBs in urine were focused on a single marker, in this study, we present a method for simultaneous determination of biomarkers of oxidative damage to lipids, proteins, and DNA. 2,4-Dinitrophenylhydrazine (DNPH) derivatization followed by solid phase extraction (SPE) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) allowed the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), o- o'-dityrosine (diY), malondialdehyde (MDA), and four F 2 -isoprostane isomers: 8-iso-prostaglandinF 2α (8-PGF 2α ), 11β-prostaglandinF 2α (11-PGF 2α ), 15( R)-prostaglandinF 2α (15-PGF 2α ), and 8-iso,15( R)-prostaglandinF 2α (8,15-PGF 2α ) in urine. Derivatization with DNPH and SPE was optimized to yield greater sensitivity and selectivity for the analysis of target chemicals. The limits of detection of target analytes in urine were below 30 pg mL -1 . The assay intra- and interday variability was below 16% of the relative standard deviation, and the recoveries of target chemicals spiked into synthetic urine were near 100%. The method was applied to the analysis of 21 real urine samples, and the analytes were found at a detection frequency of 85% for 8-PGF 2α and 15-PGF 2α , 71% for 11-PGF 2α , 81% for 8,15-PGF 2α , and 100% for diY, 8-OHdG, and MDA. This method offers simultaneous determination of multiple OSBs of different molecular origin in urine samples selectively with high accuracy and precision.

Clinical and Biochemical Influence of Prostatic Stones.

PubMed

Soric, Tomislav; Selimovic, Mirnes; Bakovic, Lada; Šimurina, Tatjana; Selthofer, Robert; Dumic, Jerka

2017-01-01

The study aimed to explore clinical influence of prostatic stones on lower urinary tract symptoms (LUTS), seminal plasma cytokines, and serum biomarkers. A total of 70 men aged ≤50 years with LUTS divided into 2 groups: group with stones (GSt) and group without prostatic stones (GNoSt). All subjects completed the International Prostate Symptom Score (IPSS) questionnaire and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scoring questionnaire. Pre- and post-prostate massage test and uroflowmetry were performed. The serum concentration of total prostate specific antigen (PSA), free PSA, and free/total PSA (f/t PSA) ratio, seminal concentration of cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-alpha were measured. GSt subjects had significantly more severe symptoms based on IPSS answers (p = 0.0289). All domains in NIH-CPSI scores were significantly higher in the GSt group: pain (p = 0.001), urinary symptoms (p = 0.023), quality of life (p = 0.008), and with overall (p = 0.003). GSt subjects also had significantly lower maximum urinary flow (Qmax; p = 0.011), lower f/t PSA ratio (p = 0.048), and higher concentration of IL-1β (p = 0.011) and IL-8 (p = 0.001). Prostatic stones may influence the severity of LUTS and the symptoms of chronic prostatitis. They might reduce Qmax rate and lead to reduction of the f/t PSA ratio and produce more severe inflammation causing increased seminal concentration of IL-1β and IL-8. © 2017 S. Karger AG, Basel.

Urinary Mineral Concentrations in European Pre-Adolescent Children and Their Association with Calcaneal Bone Quantitative Ultrasound Measurements †

PubMed Central

Van den Bussche, Karen; Herrmann, Diana; De Henauw, Stefaan; Kourides, Yiannis A.; Lauria, Fabio; Marild, Staffan; Molnár, Dénes; Moreno, Luis A.; Veidebaum, Toomas; Ahrens, Wolfgang; Sioen, Isabelle

2016-01-01

This study investigates differences and associations between urinary mineral concentrations and calcaneal bone measures assessed by quantitative ultrasonography (QUS) in 4322 children (3.1–11.9 years, 50.6% boys) from seven European countries. Urinary mineral concentrations and calcaneal QUS parameters differed significantly across countries. Clustering revealed a lower stiffness index (SI) in children with low and medium urinary mineral concentrations, and a higher SI in children with high urinary mineral concentrations. Urinary sodium (uNa) was positively correlated with urinary calcium (uCa), and was positively associated with broadband ultrasound attenuation and SI after adjustment for age, sex and fat-free mass. Urinary potassium (uK) was negatively correlated with uCa but positively associated with speed of sound after adjustment. No association was found between uCa and QUS parameters after adjustment, but when additionally adjusting for uNa, uCa was negatively associated with SI. Our findings suggest that urinary mineral concentrations are associated with calcaneal QUS parameters and may therefore implicate bone properties. These findings should be confirmed in longitudinal studies that include the food intake and repeated measurement of urinary mineral concentrations to better estimate usual intake and minimize bias. PMID:27164120

Predictors of Urinary Bisphenol A and Phthalate Metabolite Concentrations in Mexican Children

PubMed Central

Lewis, Ryan C.; Meeker, John D.; Peterson, Karen E.; Lee, Joyce M.; Pace, Gerry G.; Cantoral, Alejandra; Téllez-Rojo, Martha Maria

2013-01-01

Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8–13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-hr. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-hr, there were statistically significant (p <0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-hr and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8–13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted. PMID:24041567

Characterization of the estrous cycle in female beluga (Delphinapterus leucas) using urinary endocrine monitoring and transabdominal ultrasound: Evidence of facultative induced ovulation.

PubMed

Steinman, K J; O'Brien, J K; Monfort, S L; Robeck, T R

2012-02-01

Recent, successful application of assisted reproductive technologies in captive beluga has resulted from the extensive study of male beluga reproductive biology. Optimization of assisted reproduction requires additional detailed knowledge of the female estrous cycle. Our specific objectives were to: (1) validate urinary immunoassays for use in this species; (2) elucidate annual ovarian cycle dynamics through the combined use of hormone excretion patterns and transabdominal ultrasound; and (3) establish whether ovulation in this species is spontaneous or induced by male factors. Ovulation was observed in four of 15 estrous cycles monitored in four adult female beluga maintained in a single-sex group. After introduction of a breeding male, ovulation was observed in six of seven estrous cycles. All estrous cycles occurred from March through June. For spontaneous ovulations (n=4), the inter-estrous interval was 34d (range 33-35d), with a follicular phase length (FPL) of 25±8d (mean±SD). For all ovulatory estrous cycles (with and without a breeding male), urinary estrogen conjugates (EC, 15.3±7.9ng/mg Cr) and ovulatory luteinizing hormone (ovLH, 17.1±6.6ng/mg Cr) concentrations both peaked on Day 0, and EC concentrations returned to baseline 8±7d later. For non-conceptive cycles, urinary progestagen (Pg) concentrations increased on Day 0 (3.5±1.7ng/mg Cr), peaked on Day+19 (19.7±17.1ng/mg Cr), and were elevated above baseline for 27±4d. Preovulatory follicular diameter and circumference on Day -2±2 (range: Day -4 to -1) from peak EC were 2.5±0.7 and 7.8±1.3cm, respectively. The FPL in non-ovulatory estrous cycles (n=11) lasted 24±10d and EC concentrations gradually declined to baseline over a 21±10d interval following the EC peak (27.8±28.8ng/mg Cr). Non-ovulatory estrous cycles were characterized by the absence of an ovLH surge and no concomitant increase in Pg concentrations above baseline excretion; the mean follicular diameter at or near peak EC was 3.1±0.8cm on Day 2 ±3d from peak EC (range: -1 to +5days from peak EC). Overall, these data confirm that captive beluga exhibit reproductive seasonality and demonstrate that the species is a facultative-induced ovulator. Copyright © 2011 Elsevier Inc. All rights reserved.

First-trimester increase in oxidative stress and risk of small-for-gestational-age fetus.

PubMed

Potdar, N; Singh, R; Mistry, V; Evans, M D; Farmer, P B; Konje, J C; Cooke, M S

2009-04-01

Investigation of increased oxidative stress in early pregnancy and association with an increased risk of small-for-gestational-age (SGA) fetus. Longitudinal case-control study. University Hospitals of Leicester NHS Trust, Leicester, UK. Low-risk pregnant women with no current or pre-existing medical illness were recruited at a large teaching hospital from 2004 to 2006. Recruitment performed at the time of the dating ultrasound scan (12+/-2 weeks of gestation). Spot urine samples collected at 12+/-2 and 28+/-2 weeks of gestation were analysed for 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) by liquid chromatography with tandem mass spectrometry). SGA was defined as birthweight <10th centile based on customised centile calculator (www.gestation.net). This identified the cases (n=55), whereas controls (n=55) were mothers whose babies were appropriate for gestational age (AGA, birthweight 10th-90th centile). Statistical analysis was performed using GraphPad Prism v.5. The relationship between maternal urinary 8-oxodG at different gestations and customised SGA was investigated by nonparametric tests. Customised SGA and AGA pregnancies. Urinary 8-oxodG concentrations were significantly increased in pregnancies with subsequent SGA compared with concentrations in normal pregnancies; 12 weeks: 2.8 (interquartile range [IQR] 1.96-3.67) versus 2.2 (IQR 1.26-3.28) pmol 8-oxodG/micromol creatinine (P=0.0007); 28 weeks: 2.21 (IQR 1.67-3.14) versus 1.68 (IQR 1.16-2.82) pmol 8-oxodG/micromol creatinine (P<0.0002). Concentrations decreased significantly between week 12 and 28 (P=0.04 and P=0.02 for controls and cases). In this study, urinary 8-oxodG at 12 and 28 weeks were elevated in SGA compared with AGA pregnancies. This may reflect early placental changes predating clinical features of SGA.

High specificity of spot urinary free metanephrines in diagnosis and prognosis of pheochromocytomas and paragangliomas by HPLC with electrochemical detection.

PubMed

Zuo, Ming; Zhen, Qianna; Zhang, Xiaoqing; Zou, Wenbi; Yang, Xiangchun; Tian, Gang; Shi, Zhenghu; Li, Qifu; Ding, Min

2018-03-01

The metanephrines (MNs) in plasma and urine were proposed as biomarkers for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). However, plasma free MNs and 24h urinary fractionated MNs were not satisfactory enough in specificity for the diagnosis of PPGLs. Moreover, the collection of 24h urine was inconvenient. This work examined the diagnostic and prognostic efficiency of free MNs in spot urine for PPGLs. We measured free MNs concentration in spot urine and plasma of 28 PPGLs patients and 155 control subjects by HPLC with electrochemical detection. Postoperative free MNs levels in spot urine and plasma of 14 PPGLs patients were also determined. Creatinine (Cr) concentration was used for the correction of urine volume. The specificity of spot urinary free MNs/Cr in the diagnosis of PPGLs was significantly higher than that of plasma free MNs [normetanephrine (NMN), 98.7% (95.4%-99.8%) vs 93.0% (87.4%-96.6%); metanephrine (MN), 93.6% (88.5%-96.9%) vs 84.5% (77.5%-90.0%)]. Meanwhile, the positive likelihood ratios for spot urinary free NMN/Cr and MN/Cr were 69.21 and 13.29, compared with 12.68 and 5.30 for plasma free NMN and MN, respectively. For the PPGLs patients underwent surgery, the plasma free MNs level appeared an abnormal elevation and yielded false-positive results for some patients. Our findings were validated in an independent cohort, resulting in the specificity of 100% for both urinary free NMN/Cr and MN/Cr, and 97.3% and 83.8% for plasma free NMN and MN, respectively. Spot urinary free MNs/Cr, superior to plasma free MNs, presented a promising biomarker for the diagnosis and prognosis of PPGLs. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial.

PubMed

Verlaet, Annelies A J; Ceulemans, Berten; Verhelst, Helene; Van West, Dirk; De Bruyne, Tess; Pieters, Luc; Savelkoul, Huub F J; Hermans, Nina

2017-03-28

Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. Clinicaltrials.gov number: NCT02700685 . Registered on 18 January 2016. EudraCT 2016-000215-32 . Registered on 4 October 2016.

The hOGG1 Ser326Cys polymorphism and male subfertility in Taiwanese patients with varicocele.

PubMed

Chen, S S-S; Chiu, L-P

2018-03-26

To investigate the association between the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene Ser326Cys polymorphism and male subfertility in Taiwanese patients with varicocele, we made a prospective study. Ninety young male patients with varicocele (group 1), 50 young male patients with subclinical varicocele (group 2) and 30 normal young male patients without varicocele (group 3) were recruited in this study. The hOGG1 null homozygous genotype (Cys/Cys) and the occurrence of a 4,977-bp deletion in mitochondrial DNA and mitochondrial copy number in spermatozoa were determined by polymerase chain reaction. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) content of DNA in the spermatozoa was measured using high-performance liquid chromatography, and total antioxidant capacity (TAC) of seminal plasma was detected electrochemically. The rates of male subfertility were 31.1% (28/90) in group 1 and 22% (11/50) in group 2. Of 39 subfertile men, 74.4% (29/39) had the hOGG1 Cys/Cys genotype. Patients in groups 1 and 2 with hOGG1 Cys/Cys genotype had significantly higher 8-OHdG content in sperm DNA, lower mitochondrial copy number in spermatozoa and lower TAC in seminal plasma than those with Ser/Ser or Ser/Cys genotype. Clinicians should pay more attention to patients with varicocele with the hOGG1 Cys/Cys genotype. © 2018 Blackwell Verlag GmbH.

Detection of DNA damage in workers exposed to JP-8 jet fuel.

PubMed

Krieg, Edward F; Mathias, Patricia I; Toennis, Christine A; Clark, John C; Marlow, Kate L; B'hymer, Clayton; Singh, Narendra P; Gibson, Roger L; Butler, Mary Ann

2012-09-18

The genotoxicity of jet propulsion fuel 8 (JP-8) was assessed in the leukocytes of archived blood specimens from U.S. Air Force personnel using the comet assay. No differences in mean comet assay measurements were found between low, moderate, and high exposure groups before or after a 4h work shift. Before the work shift, mean tail DNA and mean tail (Olive) moment increased as the concentration of benzene measured in end-exhaled breath increased, indicating that prior environmental or work-related exposures to benzene produced DNA damage. The number of cells with highly damaged DNA decreased as the pre-shift benzene concentration in breath increased. It is not clear why the decrease is occurring. Mean tail DNA and mean tail (Olive) moment decreased as the concentrations of benzene and naphthalene measured in breath immediately after the work shift increased. These inverse relationships may reflect a slower rate of absorption or a faster rate of expiration of benzene in the lung. The number of cells with highly damaged DNA increased as the concentration of urinary (2-methoxyethoxy)acetic acid (MEAA) increased. This relationship was not seen in urinary MEAA adjusted for creatinine. MEAA is a metabolite of the deicing agent 2-(2-methoxyethoxy)ethanol contained in JP-8. MEAA or a component of JP-8 correlated with MEAA may have a toxic effect on DNA. Published by Elsevier B.V.

Effects of Dietary Iron and Gamma Radiation on the Rat Retina

NASA Technical Reports Server (NTRS)

Morgan, Jennifer; Marshall, Grace; Theriot, Corey A.; Chacon, Natalia; Zwart, Sara; Zanello, Susana B.

2012-01-01

A health risk of concern for NASA relates to radiation exposure and its synergistic effects with other space environmental factors, includi ng nutritional status of the crew. Astronauts consume almost three times the recommended daily allowance of iron due to the use of fortifie d foods aboard the International Space Station, with iron intake occa sionally exceeding six times the recommended values. Recently, NASA has become concerned with visual changes associated with spaceflight, a nd research is being conducted to elucidate the etiology of eye structure alterations in the spaceflight environment. Terrestrially, iron o verload is also associated with certain optic neuropathies. In additi on, due to its role in Fenton reactions, iron can potentiate oxidative stress, which is a recognized cause of cataract formation. As part o f a study investigating the combined effects of radiation exposure an d iron overload on multiple physiological systems, we focused on defining the effects of both treatments on eye biology. In this study, 12- week-old Sprague-Dawley rats were assigned to one of four experimental groups: normal iron/no radiation (Control/Sham), high iron/no radiat ion (Fe/Sham), normal iron/gamma radiation (3 Gy cumulative dose, fra ctionated at 0.375 Gy/d every other day for 16 d) (Control/Rad), and high iron/gamma radiation (Fe/Rad). Oxidative stress-induced DNA damag e, measured as concentration of the marker 8-hydroxy-2'-deoxyguanosine (8OHdG) in eye retinal tissue by enzyme-immunoanalysis did not show significant changes among treatments. However, there was an overall i ncrease in 8OHdG immunostaining density in retina sections due to radiation exposure (P = 0.05). Increased dietary iron and radiation expos ure had an interactive effect (P = 0.02) on 8OHdG immunostaining of t he retinal ganglion cell layer with iron diet increasing the signal in the group not exposed to radiation (P = 0.05). qPCR gene expression profiling of relevant target genes indicated upregulation of ferritin light chain (P = 0.09) as a result of dietary iron but no change in e xpression of the gene for ferritin heavy chain. Immunolocalization of light chain and heavy chain of the iron storage protein ferritin showed the expected distribution in the choroid, photoreceptor layer, inn er nuclear layer and in the inner plexiform layer that corresponded t o the synaptic terminals of bipolar cells. Evidence of stress and damage in the retina was also suggested by a decrease in expression of th e survival marker Bcl2 (P = 0.01) and the protective proteins clusterin (P = 0.04) and heat shock factor 1 (Hsf1, P < 0.001), as a result o f increased dietary iron. The effect of increased iron on expression of the antioxidant enzyme heme oxygenase 1 (Hmox1) had a significant interaction with the effect of radiation (P < 0.001). In summary, the results of this study indicate that both gamma radiation exposure and a moderate increase in dietary iron can contribute to deleterious cha nges in retinal health and physiology.

Uptake and immunomodulatory role of bixin in dogs.

PubMed

Park, J S; Mathison, B D; Chew, B P

2016-01-01

Carotenoids are readily absorbed from the diet and distributed in blood leukocyte subcellular organelles. Bixin, a potent bioactive found in the seed of the Annatto plant, , possesses antioxidant and anti-inflammatory properties. The purpose of this study was to determine the uptake of bixin by plasma, lipoproteins, and leukocytes in domestic dogs and to examine immunoprotective properties. To determine uptake kinetics, female Beagle dogs (2 yr; 9.1 ± 0.1 kg BW) were first fed a single dose by oral gavage of 0, 5, 10, 20, or 40 mg bixin, with blood collected at 0 to 16 h after administration ( = 6/treatment), and then fed daily with 0, 5, 10, 20, or 40 mg bixin/d, with blood collected at 0, 1, 2, 4, 6, 10, and 14 d. In a consecutive experiment, cell-mediated and humoral responses as well as oxidative biomarkers were measured following 16 wk of dietary supplementation with 0, 5, 10, or 20 mg bixin/d. Maximal absorption in plasma occurred by 0.5 h with an elimination half-life of 2.6 to 3.3 h after a single dose of bixin. Steady-state plasma concentrations were 0.053 μ after 14 d of 40 mg bixin/d. The majority of subcellular bixin was found in the leukocyte mitochondria and was associated with the high-density lipoprotein and low-density lipoprotein fractions of lipoproteins. Specific (vaccine) response increased ( < 0.05) but nonspecific mitogen response was unchanged after 12 wk of dietary bixin, as assessed by a delayed-type hypersensitivity assay. Both B cell plasma leukocyte subpopulations at 6 and 16 wk and IgG plasma concentration at 12 wk in the 10-mg treatment group increased ( < 0.05), although IgM production and other cell populations were unaffected. In addition, 8-oxo-2'-deoxyguanosine (8-OHdG), a DNA damage biomarker, was substantially reduced ( < 0.05) in all treatment groups by wk 16, and C-reactive protein (CRP) was suppressed at wk 12 ( < 0.05). Dietary supplementation with bixin showed no changes in lymphoproliferation in response to in vitro mitogenic challenge and had no effect in enhancing natural killer cell activity. In conclusion, bixin was readily absorbed in a dose-dependent manner in blood following oral administration and was then taken up by leukocytes, where it was primarily distributed to mitochondria but in other subcellular organelles as well. Bixin also appeared to stimulate immune response, as seen with cell-mediated responses, and exerted anti-inflammatory (reduced CRP) as well as antioxidative (reduced 8-OHdG) effects in dogs.

[Local application of dimethyl sulfoxide at different concentrations to the prevention of radiation-induced damages in patient with cancer of the cervix uteri].

PubMed

Neklasova, N Iu; Sharinov, G M; Vinokurov, V L; Skrynditsa, G M

2006-01-01

to study the efficacy of dimethyl sulfoxide ((DMSO) at different concentrations in preventing radiation-induced rectal and urinary bladder damages in patients with cervix uteri cancer (CUC). combined radiation therapy (RT) was performed in 807 patients with CUC. In the control group (n = 221), RT was made, without applying radio-modified agents. An hour prior to a session of intracavitary irradiation, 10% DMSO solution was instilled into the rectum and urinary bladder in 113 patients and applications of metronidazole (MN) dissolved in 100% DSMO were made in 473 patients. Teleradiotherapy was performed, by using megavolt irradiation sources in the conventional fractionation mode; the total focal dose (TFD) was increased up to 40-46 Gy. Intracavitary irradiation was carried out on "AGAT-V" and "AGAT-VU" devices once weekly; the single focal dose in point A was 7 Gy; TFD was 49-56 Gy. 10% DMSO instillations reduced the incidence of late radiation-induced damages to the rectum and urinary bladder. In the control group, the incidence of these conditions was 19.0 and 9.5%, respectively; with the use of 10% DMSO, that was 8.8 and 7.1%. Applications of MN dissolved in 100% DMSO reduced the incidence of late radiation-induced damages to 1.7%. Local application of DMSO is a method for preventing late radiation-induced damages to the rectum and urinary bladder in patients with CUC. When the concentration of DMSO is increased, its preventive effect increases.

Urinary 1-hydroxypyrene concentrations in coke oven workers

PubMed Central

Wu, M. T.; Mao, I. F.; Ho, C. K.; Wypij, D.; Lu, P. L.; Smith, T. J.; Chen, M. L.; Christiani, D. C.

1998-01-01

OBJECTIVES: To investigate the relation of individual occupational exposure to total particulates benzene soluble fraction (BSF) of ambient air with urinary 1-hydroxypyrene (1-OHP) concentrations among coke oven workers in Taiwan. METHODS: 80 coke oven workers and 50 referents were monitored individually for the BSF of breathing zone air over three consecutive days. Exposures were categorised as high, medium, or low among coke oven workers based on exposure situations. The high exposure group (n = 18) worked over the oven. The medium and low exposure groups (n = 41 and n = 21) worked at the side of the oven for > 4 hours and < 4 hours a day, respectively. Urine was collected before the shift on the morning of day 1 and after the shift on the afternoon of day 3 to find the change of 1-OHP concentrations across the shift. RESULTS: The median (range) changes of urinary 1-OHP concentrations across the shift for various exposure situations (microgram/g creatinine) were as follows: high 182 (7 to 3168); medium 9 (-8 to 511); low 7 (-6 to 28); and referents 0.2 (-2 to 72). This change of urinary 1-OHP was highly associated with individual occupational exposure to the BSF in air (r = 0.74 and 0.64, p < 0.001). The regression model showed significant effects of individual exposures to the BSF and alcohol consumption on urinary postshift 1-OHP after adjusting for preshift 1-OHP in the total population (n = 130). More exposure to the BSF led to higher postshift 1-OHP (p < 0.001); current drinkers of > 120 g/week had lower urinary postshift 1-OHP than never and former drinkers (p = 0.01). A 10-fold increase in the average BSF in air resulted in about a 2.5-fold increase in postshift 1-OHP among the 80 coke oven workers. CONCLUSION: Urinary 1-OHP concentrations can be used as a good biomarker to assess individual exposure to the BSF in air. Alcohol drinking may modify the toxicokinetic pathway of the BSF; the effects of alcohol should be investigated further in occupational studies.   PMID:9816379

Exposure to different sources of second-hand smoke during pregnancy and its effect on urinary cotinine and tobacco-specific nitrosamine (NNAL) concentrations.

PubMed

Vardavas, Constantine I; Fthenou, Eleni; Patelarou, Evridiki; Bagkeris, Emmanouil; Murphy, Sharon; Hecht, Stephen S; Connolly, Gregory N; Chatzi, Leda; Kogevinas, Manolis

2013-05-01

To date, no research exists on the role that different sources of exposure to second-hand smoke (SHS) have on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine uptake, assessed via urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cotinine concentrations of non-smoking pregnant women, nor the differences in NNAL concentrations among pregnant women who quit smoking in comparison to those who do not. As part of the 'Rhea' mother childbirth cohort in Crete, Greece, 1317 mother-child pairs were followed-up until delivery, while among a subsample, maternal urine was assessed for its NNAL (n=117) and cotinine concentrations (n=377). Pregnant women who continued to smoke during pregnancy were found to have geometric mean urinary NNAL concentrations of 0.612 pmol/ml, in comparison to the 0.100 pmol/ml of ex-smokers and 0.0795 pmol/ml of non-smokers exposed to SHS. Exposure to SHS in the home was associated with a 4.40 ng/ml increase in urinary cotinine levels, while reported exposure to SHS in cars was associated with an even higher (8.73 ng/ml) increase in cotinine concentrations and was strongly related to NNAL concentrations. Exposure to SHS in the workplace and in public places was also shown to increase cotinine and NNAL concentrations. The NNAL:cotinine ratio was found to be higher among pregnant women who were exposed to SHS but did not smoke (p<0.001). Using cotinine levels as an indicator of NNK, exposure due to SHS during pregnancy leads to an underestimation of exposure to NNK uptake. Moreover, each source of exposure contributed to the increase in cotinine levels, indicating the importance of avoiding SHS exposure from any source.

Plasma asymmetric dimethylarginine (ADMA) levels in Mexican women exposed to polycyclic aromatic hydrocarbons (PAHs): A preliminary study.

PubMed

Pruneda-Alvarez, Lucía G; Ruíz-Vera, Tania; Ochoa-Martínez, Angeles C; Pérez-Vázquez, Francisco J; González Palomo, Ana K; Ilizaliturri-Hernández, Cesar A; Pérez-Maldonado, Iván N

2016-12-01

Recent studies indicate that exposure to environmental pollutants (as polycyclic aromatic hydrocarbons) is a very important risk factor for development of cardiovascular diseases (CVDs). Correspondingly, in recent times asymmetric dimethylarginine (ADMA) has been proposed as a new and meaningful biomarker predictor for the risk of CVDs. Therefore, the objective of this study was to evaluate plasma ADMA concentrations in Mexican women (n=155) exposed to polycyclic aromatic hydrocarbons (PAHs). Urinary 1-hydroxypyrene [(1-OHP), exposure biomarker for PAHs] levels were quantified using a high performance liquid chromatography (HPLC) technique and plasma ADMA concentrations were analyzed using a commercially available ELISA kit. Urinary 1-OHP levels in all women assessed ranged from

Klotho and S100A8/A9 as Discriminative Markers between Pre-Renal and Intrinsic Acute Kidney Injury

PubMed Central

Kim, Ae Jin; Ro, Han; Kim, Hyunsook; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Jung, Ji Yong

2016-01-01

Early detection and accurate differentiation of the cause of AKI may improve the prognosis of the patient. However, to date, there are few reliable biomarkers that can discriminate between pre-renal and intrinsic AKI. In this study, we determined whether AKI is associated with altered serum and urinary levels of Klotho, S100A8/A9 (an endogenous ligand of toll-like receptor 4), and neutrophil gelatinase-associated lipocalin (NGAL), which may allow differentiation between pre-renal and intrinsic AKI. A volume-depleted pre-renal AKI model was induced in male Sprague Dawley rats fed a low-salt diet (0.03%) without water 96 h before two intraperitoneal (IP) injections of furosemide (20 mg/kg) at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model, animals were given a single IP injection of cisplatin (5 mg/kg). All of the animals were euthanized 72 h after the first IP injection. Serum and urinary levels of Klotho, S100A8/A9, and NGAL were measured using an enzyme-linked immunosorbent assay. We also performed a proof-of-concept cross-sectional study to measure serum and urinary biomarkers in 61 hospitalized patients with established AKI. Compared to the intrinsic AKI group, the pre-renal AKI group showed a marked depression in urinary Klotho levels (13.21±17.32 vs. 72.97±17.96 pg/mL; P = 0.002). In addition, the intrinsic AKI group showed marked elevation of S100A8/A9 levels compared to the pre-renal AKI group (2629.97±598.05 ng/mL vs. 685.09±111.65 ng/mL; P = 0.002 in serum; 3361.11±250.86 ng/mL vs. 741.72±101.96 ng/mL; P = 0.003 in urine). There was no difference in serum and urinary NGAL levels between the pre-renal and intrinsic AKI groups. The proof-of-concept study with the hospitalized AKI patients also demonstrated decreased urinary Klotho in pre-renal AKI patients and increased urinary S100A8/A9 concentrations in intrinsic AKI patients. The attenuation of urinary Klotho and increase in urinary S100A8/A9 may allow differentiation between pre-renal and intrinsic AKI. PMID:26799323

Grape seed proanthocyanidin extract protects human umbilical vein endothelial cells from indoxyl sulfate-induced injury via ameliorating mitochondrial dysfunction.

PubMed

Lu, Zhaoyu; Lu, Fuhua; Zheng, Yanqun; Zeng, Yuqun; Zou, Chuan; Liu, Xusheng

2016-01-01

To investigate the effects of grape seed proanthocyanidin extract (GSPE) on indoxyl sulfate-induced Human Umbilical Vein Endothelial Cells (HUVECs) injury in vitro and study its mechanism. HUVECs were incubated with indoxyl sulfate at concentrations in the range found in uremic patients. Then we determined the effect of indoxyl sulfate on endothelial phenotype, endothelial function, ROS (reactive oxygen species), cell apoptosis and mitochondrial function. In addition, we detected whether GSPE can suppress the injury of HUVECs induced by indoxyl sulfate and probe the mechanism underlying the protective effects of GSPE by analyzing mitochondrial dysfunction. GSPE treatment significantly attenuated indoxyl sulfate-induced HVUECs injury in a dose- and time-dependent manner. GSPE-enhanced eNOS and VE-cadherin expression, inhibited intracellular ROS level and cell apoptosis, adjust mitochondrial membrane potential and reduced 8-hydroxy-desoxyguanosine (8-OHdG) level induced by indoxyl sulfate. These results suggest that GSPE prevents HUVECs from indoxyl sulfate-induced injury by ameliorating mitochondrial dysfunction and may be a promising agent for treating uremia toxin-induced injury.

Specific histone modification responds to arsenic-induced oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Lu

To explore whether specific histone modifications are associated with arsenic-induced oxidative damage, we recruited 138 arsenic-exposed and arsenicosis subjects from Jiaole Village, Xinren County of Guizhou province, China where the residents were exposed to arsenic from indoor coal burning. 77 villagers from Shang Batian Village that were not exposed to high arsenic coal served as the control group. The concentrations of urine and hair arsenic in the arsenic-exposure group were 2.4-fold and 2.1-fold (all P < 0.001) higher, respectively, than those of the control group. Global histone modifications in human peripheral lymphocytes (PBLCs) were examined by ELISA. The results showedmore » that altered global levels of H3K18ac, H3K9me2, and H3K36me3 correlated with both urinary and hair-arsenic levels of the subjects. Notably, H3K36me3 and H3K18ac modifications were associated with urinary 8-OHdG (H3K36me3: β = 0.16; P = 0.042, H3K18ac: β = − 0.24; P = 0.001). We also found that the modifications of H3K18ac and H3K36me3 were enriched in the promoters of oxidative stress response (OSR) genes in human embryonic kidney (HEK) cells and HaCaT cells, providing evidence that H3K18ac and H3K36me3 modifications mediate transcriptional regulation of OSR genes in response to NaAsO{sub 2} treatment. Particularly, we found that reduced H3K18ac modification correlated with suppressed expression of OSR genes in HEK cells with long term arsenic treatment and in PBLCs of all the subjects. Taken together, we reveal a critical role for specific histone modification in response to arsenic-induced oxidative damage. - Highlights: • H3K18ac, H3K9me2 and H3K36me3 were associated with arsenic exposed levels. • H3K18ac and H3K36me3 were correlated with oxidative damage induced by arsenic. • H3K18ac and H3K36me3 might involve in transcriptional regulation of OSR genes. • Dysregulation of H3K18ac and H3K36me3 might be biomarkers of arsenic toxicity.« less

EXCRETION OF ARSENIC IN URINE AS A FUNCTION OF EXPOSURE TO ARSENIC IN DRINKING WATER

EPA Science Inventory

Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first mornin...

Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study.

PubMed

Ditscheid, B; Fünfstück, R; Busch, M; Schubert, R; Gerth, J; Jahreis, G

2005-06-01

The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects. A randomized placebo-controlled double-blind intervention study with cross-over design. Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. Eight female patients with chronic urinary tract infection and 12 healthy women (controls). After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks. Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate. Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/-4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30 micromol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 micromol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent such an increase.

Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort.

PubMed

Gossai, Anala; Lesseur, Corina; Farzan, Shohreh; Marsit, Carmen; Karagas, Margaret R; Gilbert-Diamond, Diane

2015-01-01

Leptin is an important pleiotropic hormone involved in the regulation of nutrient intake and energy expenditure, and is known to influence body weight in infants and adults. High maternal levels of arsenic have been associated with reduced infant birth weight, but the mechanism of action is not yet understood. This study aimed to investigate the association between in utero arsenic exposure and infant cord blood leptin concentrations within 156 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) who were exposed to low to moderate levels of arsenic through well water and diet. In utero arsenic exposure was obtained from maternal second trimester urinary arsenic concentration, and plasma leptin levels were assessed through immunoassay. Results indicate that urinary arsenic species concentrations were predictive of infant cord blood leptin levels following adjustment for creatinine, infant birth weight for gestational age percentile, infant sex, maternal pregnancy-related weight gain, and maternal education level amongst 149 white mother-infant pairs in multivariate linear regression models. A doubling or 100% increase in total urinary arsenic concentration (iAs+MMA+DMA) was associated with a 10.3% (95% CI: 0.8-20.7%) increase in cord blood leptin levels. A 100% increase in either monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA) was also associated with an 8.3% (95% CI: -1.0-18.6%) and 10.3% (95% CI: 1.2-20.2%) increase in cord blood leptin levels, respectively. The association between inorganic arsenic (iAs) and cord blood leptin was of similar magnitude and direction as other arsenic species (a 100% increase in iAs was associated with a 6.5% (95% CI: -3.4-17.5%) increase in cord blood leptin levels), albeit not significant. These results suggest in utero exposure to low levels of arsenic influences cord blood leptin concentration and presents a potential mechanism by which arsenic may impact early childhood growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to organophosphorus pesticides in Norwegian mothers and their children: Diurnal variability in concentrations of their biomarkers and associations with food consumption.

PubMed

Cequier, Enrique; Sakhi, Amrit Kaur; Haug, Line Småstuen; Thomsen, Cathrine

2017-07-15

Several studies have suggested that exposure to organophosphorus (OP) pesticides is detrimental for health, and in particular for children where moderate doses may have a negative impact on the neurodevelopment. This study surveys levels of the 6 non-specific urinary metabolites (dialkyl phosphates (DAPs)) of OP pesticides in Norwegian mothers (n=48) and their children (n=54), and examines the diurnal variation in concentrations as well as associations with consumption of specific food products. The highest median concentration measured in urine was found for dimethyl thiophosphate (5.3 and 5.5ng/mL SG ; specific gravity corrected) for both children and mothers, respectively, followed by diethyl phosphate (3.8 and 5.3ng/mL SG , respectively). The intra-class correlation coefficients of DAPs among mothers were moderate (0.49-0.68), and consumption of fruit explained between 8% and 55% of the variations in the mothers' and their children's urinary DAP concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

Decreased Urinary Sodium-to-urinary Creatinine Ratio Identifies Sodium Depletion in Pediatric Acute Gastroenteritis.

PubMed

Heinz-Erian, P; Akdar, Z; Haerter, B; Waldegger, S; Giner, T; Scholl-Bürgi, S; Mueller, T

2016-01-01

In acute gastroenteritis (AG) fecal losses may cause depletion of sodium (NaD) which may not be recognized because of normal plasma Na (pNa) concentrations. We studied the incidence of this state of normonatremic sodium depletion (NNaD) and the suitability of the urinary Na/urinary creatinine ratio (uNa/uCr) for diagnosing NNaD. 16 AG- and 16 healthy control children aged 0.8-15.0 years. Prospective cross sectional pilot study. Measurements of Na, K and creatinine in plasma (p) and urine (u). Calculation of uNa/uCr Ratio, fractional excretion of Na (FENa) and uNa/uK ratio as the hitherto best known parameters of prerenal Na depletion, respectively. pNa concentrations were normal in 15/16 AG patients (93.8%) with only one subnormal value of 133 mmol/L, and a mean value of 137.9±2.3 mmol/L not different from the normal control group (139.4±2.2 mmol/L). Also, mean uNa concentrations and uNa/uK ratios did not differ between both groups. However, uNa/uCr ratios were below normal in 13/16 AG children (81.3%) but normal in all healthy controls with a significantly lower mean value in the AG group (12.6±8.8 vs. 31.2±8.3 mmol/mmol; p<0.0001). Similarly, 14/16 AG patients (87.5%) had a decreased FENa<0.5% with a mean FENa value significantly lower than in controls (0.36±0.28% vs. 0.95±0.26%, p<0.0001). The good agreement between FENa and uNa/uCr results was also reflected by a high correlation coefficient of r=0.9333. The majority of AG patients was found to have NNaD as determined by uNa/uCr and FENa. Calculation of uNa/uCr may be useful for diagnosing NNaD in AG. © Georg Thieme Verlag KG Stuttgart · New York.

Urinary Paraben Concentrations and Ovarian Aging among Women from a Fertility Center

PubMed Central

Smith, Kristen W.; Souter, Irene; Dimitriadis, Irene; Ehrlich, Shelley; Williams, Paige L.; Calafat, Antonia M.

2013-01-01

Background: Parabens are preservatives commonly used in personal care products, pharmaceuticals, and foods. There is documented widespread human exposure to parabens, and some experimental data suggest that they act as estrogenic endocrine disruptors. As far as we are aware, no epidemiologic studies have assessed female reproductive health effects in relation to paraben exposure. Objective: We examined the association of urinary paraben concentrations with markers of ovarian reserve in a prospective cohort study of women seeking fertility treatment at Massachusetts General Hospital, Boston, Massachusetts. Methods: Measures of ovarian reserve were day-3 follicle-stimulating hormone (FSH), antral follicle count (AFC), and ovarian volume. Paraben concentrations [methylparaben (MP), propylparaben (PP), and butylparaben (BP)] were measured in spot urine samples collected prior to the assessment of outcome measures. We used linear and Poisson regression models to estimate associations of urinary paraben concentrations (in tertiles) with ovarian reserve measures. Results: Of the women enrolled in 2004–2010, 192 had at least one ovarian reserve outcome measured (mean age ± SD, 36.1 ± 4.5 years; range, 21.0–46.7 years). MP and PP were detected in > 99% of urine samples and BP in > 75%. We found a suggestive trend of lower AFC with increasing urinary PP tertiles [mean percent change (95% CI) for tertiles 2 and 3 compared with tertile 1, respectively, were –5.0% (–23.7, 18.4) and –16.3% (–30.8, 1.3); trend p-value (ptrend) = 0.07] as well as higher day-3 FSH with higher urinary PP tertiles [mean change (95% CI) for tertiles 2 and 3 compared with tertile 1 were 1.16 IU/L (–0.26, 2.57) and 1.02 IU/L (–0.40, 2.43); ptrend = 0.16]. We found no consistent evidence of associations between urinary MP or BP and day-3 FSH or AFC, or between urinary MP, PP, or BP and ovarian volume. Conclusions: PP may be associated with diminished ovarian reserve. However, our results require confirmation in further studies. Citation: Smith KW, Souter I, Dimitriadis I, Ehrlich S, Williams PL, Calafat AM, Hauser R. 2013. Urinary paraben concentrations and ovarian aging among women from a fertility center. Environ Health Perspect 121:1299–1305; http://dx.doi.org/10.1289/ehp.1205350 PMID:23912598

Oxidative Stress Parameters in Saliva and Its Association with Periodontal Disease and Types of Bacteria.

PubMed

Almerich-Silla, Jose Manuel; Montiel-Company, Jose María; Pastor, Sara; Serrano, Felipe; Puig-Silla, Miriam; Dasí, Francisco

2015-01-01

To determine the association between oxidative stress parameters with periodontal disease, bleeding, and the presence of different periodontal bacteria. A cross-sectional study in a sample of eighty-six patients, divided into three groups depending on their periodontal status. Thirty-three with chronic periodontitis, sixteen with gingivitis, and thirty-seven with periodontal healthy as control. Oxidative stress biomarkers (8-OHdG and MDA), total antioxidant capacity (TAOC), and the activity of two antioxidant enzymes (GPx and SOD) were determined in saliva. Subgingival plaque samples were obtained from the deepest periodontal pocket and PCR was used to determine the presence of the 6 fimA genotypes of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, and Treponema denticola. Periodontal disease was found to be associated with increased oxidative stress parameter levels. These levels rose according to the number and type of different periodontal bacteria found in the periodontal pockets. The presence of different types of periodontal bacteria is predictive independent variables in linear regresion models of oxidative stress parameters as dependent variable, above all 8-OHdG. Oxidative stress parameter levels are correlated with the presence of different types of bacteria. Determination of these levels and periodontal bacteria could be a potent tool for controlling periodontal disease development.

Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

PubMed

Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

2016-12-01

Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

PubMed

Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

2017-09-11

Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age

PubMed Central

Papandonatos, George D.; Calafat, Antonia M.; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P.; Yolton, Kimberly; Braun, Joseph M.

2017-01-01

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother–child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1–8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate–adiposity associations at each visit, test differences in phthalate–adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): −4.8, −0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 PMID:28935615

The effects of concentrate added to pineapple (Ananas comosus Linn. Mer.) waste silage in differing ratios to form complete diets, on digestion, excretion of urinary purine derivatives and blood metabolites in growing, male, Thai swamp buffaloes.

PubMed

Jetana, T; Suthikrai, W; Usawang, S; Vongpipatana, C; Sophon, S; Liang, J B

2009-04-01

Four, male, growing Thai swamp buffaloes (197 +/- 5.3 kg and all 1 year old) were used to evaluate the effects of concentrate added to pineapple waste silage in differing ratios, to form a complete diet, studying in vivo digestion, the rate of passage, microbial protein synthesis and blood metabolites. Animals were fed ad libitum with 4 diets, using four combinations of pineapple waste silage (P) and concentrate (C), in the proportions (on a dry matter basis) of 0.8:0.2 (P80:C20), 0.6:0.4 (P60:C40), 0.4:0.6 (P40:C60) and 0.2:0.8 (P20:C80). The results showed that the intakes of dry matter (DM), organic matter (OM), nitrogen (N), the N-balance, urinary purine derivatives (PD) excretion, the ratios of allantoin to creatinine (CR), PD to CR, the plasma urea-N (PUN) and insulin increased in the animals, but the intake of neutral detergent fiber (NDF), the coefficient of whole tract, apparent digestibility of NDF, the transit time (TT) and the mean retention time (TMRT) decreased, when the proportion of concentrate in the diet increased. This study indicated that the proportion of P40:C60 in the diet produced the best efficiency of urinary PD excretion (mmol) per digestible OM intake (kg DOMI).

Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations.

PubMed

Roberge, Jason; O'Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L; Harris, Robin B

2012-04-01

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

PubMed Central

Roberge, Jason; O’Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L.; Harris, Robin B.

2012-01-01

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated. PMID:22690182

Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways

PubMed Central

Pan, Xiao-Qing; Gonzalez, Jessica A.; Chang, Shaohua; Chacko, Samuel; Wein, Alan J.; Malykhina, Anna P.

2010-01-01

Clinical data provides evidence of high level of co-morbidity among genitourinary and gastrointestinal disorders characterized by chronic pelvic pain. The objective of this study was to test the hypothesis that colonic inflammation can impact the function of the urinary bladder via activation of TRPV1 signaling pathways followed by alterations in gene and protein expression of Substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory neurons and in the bladder. Inflammation was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS, 12.5 mg/kg) and desensitization of TRPV1 receptors was evoked by intracolonic resiniferatoxin (RTX, 10−7 M). mRNA and protein concentrations of CGRP and SP were measured at 3, 5 and 30 days. RTX instillation in the colon caused 3-fold up-regulation of SP mRNA in the urinary bladder at day 5 (n=7, p≤0.05) followed by 35-fold increase at day 30 (n=5, p≤0.05). Likewise, TNBS colitis triggered 15.8-fold up-regulation of SP mRNA one month after TNBS (n=5, p≤0.05). Desensitization of colonic TRPV1 receptors prior to TNBS abolished SP increase in the urinary bladder. RTX led to 4.3-fold increase of CGRP mRNA at day 5 (n=7, p≤0.05 to control) in the bladder followed by 28-fold increase at day 30 post-RTX (n=4, p≤0.05). Colitis did not alter CGRP concentration during acute phase, however, at day 30 mRNA level was increased by 17.8±6.9 fold (n=5, p≤0.05) in parallel with 4-fold increase in CGRP protein (n=5, p≤0.01) in the detrusor. Protein concentration of CGRP in the spinal cord was diminished by 45–65% (p≤0.05) during colitis. RTX pretreatment did not affect CGRP concentration in the urinary bladder, however, caused a reduction in CGRP release from lumbosacral DRG neurons during acute phase (3 and 5 days post-TNBS). Our results clearly demonstrate that colonic inflammation triggers the release of pro-inflammatory neuropeptides SP and CGRP in the urinary bladder via activation of TRPV1 signaling mechanisms enunciating the neurogenic nature of pelvic organ cross-sensitization. PMID:20501335

Prenatal and Postnatal Bisphenol A Exposure and Body Mass Index in Childhood in the CHAMACOS Cohort

PubMed Central

Schall, Raul Aguilar; Chevrier, Jonathan; Tyler, Kristin; Aguirre, Helen; Bradman, Asa; Holland, Nina T.; Lustig, Robert H.; Calafat, Antonia M.; Eskenazi, Brenda

2013-01-01

Background: Bisphenol A (BPA), a widely used endocrine-disrupting chemical, has been associated with increased body weight and fat deposition in rodents. Objectives: We examined whether prenatal and postnatal urinary BPA concentrations were associated with body mass index (BMI), waist circumference, percent body fat, and obesity in 9-year-old children (n = 311) in the CHAMACOS longitudinal cohort study. Methods: BPA was measured in spot urine samples collected from mothers twice during pregnancy and from children at 5 and 9 years of age. Results: Prenatal urinary BPA concentrations were associated with decreased BMI at 9 years of age in girls but not boys. Among girls, being in the highest tertile of prenatal BPA concentrations was associated with decreased BMI z-score (β = –0.47, 95% CI: –0.87, –0.07) and percent body fat (β = –4.36, 95% CI: –8.37, –0.34) and decreased odds of overweight/obesity [odds ratio (OR) = 0.37, 95% CI: 0.16, 0.91] compared with girls in the lowest tertile. These findings were strongest in prepubertal girls. Urinary BPA concentrations at 5 years of age were not associated with any anthropometric parameters at 5 or 9 years, but BPA concentrations at 9 years were positively associated with BMI, waist circumference, fat mass, and overweight/obesity at 9 years in boys and girls. Conclusions: Consistent with other cross-sectional studies, higher urinary BPA concentrations at 9 years of age were associated with increased adiposity at 9 years. However, increasing BPA concentrations in mothers during pregnancy were associated with decreased BMI, body fat, and overweight/obesity among their daughters at 9 years of age. PMID:23416456

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-06-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively.

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed Central

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-01-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively. PMID:12782488

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores.

PubMed

Pesch, Beate; Lotz, Anne; Koch, Holger M; Marczynski, Boleslaw; Casjens, Swaantje; Käfferlein, Heiko U; Welge, Peter; Lehnert, Martin; Heinze, Evelyn; Van Gelder, Rainer; Hahn, Jens-Uwe; Behrens, Thomas; Raulf, Monika; Hartwig, Andrea; Weiss, Tobias; Brüning, Thomas

2015-08-01

The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxidatively damaged guanosine in DNA of white blood cells (WBC) and in postshift urine samples from 238 welders. Medians of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were 2.35/10(6) dGuo in DNA of WBC and 4.33 µg/g creatinine in urine. The median of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 7.03 µg/g creatinine in urine. The extent of both urinary parameters was higher in welders applying techniques with high particle emission rates to stainless steel than in tungsten inert gas welders (8-oxodGuo: 9.96 vs. 4.49 µg/L, 8-oxoGuo: 15.7 vs. 7.7 µg/L), but this apparent difference diminished after creatinine adjustment. We applied random intercept models to estimate the influence of airborne and systemic exposure to metals on oxidatively damaged guanosine in WBC and urine together with covariates. We observed a highly significant nonlinear association of urinary 8-oxoGuo with serum ferritin (P < 0.0001) and higher 8-oxoGuo concentrations for respirable iron >1,000 µg/m(3) compared to ≤57 µg/m(3). Similar effects were found for manganese. Airborne chromium but not nickel was associated with all oxidatively modified guanosine measures, whereas urinary chromium as well as nickel showed associations with urinary modified guanosines. In summary, oxidatively damaged urinary guanosine was associated with airborne and systemic exposure to metals in welders and showed a strong relation to body iron stores.

Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium

PubMed Central

Chalkley, S. R.; Richmond, J.; Barltrop, D.

1998-01-01

OBJECTIVES: To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. METHODS: Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25- dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. RESULTS: Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6- 145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium. CONCLUSION: Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium concentration of the urine, (regression coefficient +0.35 SE 0.077). Exposure to cadmium alone decreased the concentrations of 1 alpha,25(OH)2D3 and 24R,25(OH)2D3, whereas exposure to both cadmium and lead increased the concentrations of 1 alpha,25(OH)2D3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D3 endocrine complex. Perturbation of the vitamin D metabolic pathway by cadmium may result in health effect, such as osteoporosis or osteomalacia, risks which are possibly increased in the presence of lead.   PMID:9816377

Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM).

PubMed

Matsumura, Mihoko; Nakatani, Yuki; Tanka, Seiichi; Aoki, Chie; Sagara, Masaaki; Yanagi, Kazunori; Suzuki, Kunihiro; Aso, Yoshimasa

2017-08-01

The efficacy of administering a sodium-glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM). The subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment. The mean glucose concentrations, standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean of daily difference of blood glucose (MODD), and area under the curve (AUC) (≥180, <70 mg h/dL) after the start of administration were compared with the pretreatment values. In addition, we compared changes in the number of insulin units between basal and bolus insulin. Furthermore, we investigated the influence of canagliflozin on oxidative stress markers and cytokines using 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), and adiponectin as parameters. The mean glucose concentrations decreased from 161.1 to 139.1 mg/dL (P < 0.01). The SD decreased from 36.5 to 29.6 mg/dL (P = 0.05). The MAGE decreased from 89.2 to 77.4 mg/dL (P < 0.01), and the MODD decreased from 34.3 to 25.5 mg/dL (P < 0.05). All parameters showed significant improvements in diurnal changes. AUC of ≥180, i.e., the total area of blood glucose levels at or above 180 on the blood glucose curve of CGM, decreased from 339.1 to 113.6 mg/dL (P < 0.05). AUC of <70, i.e., the total area of blood glucose levels below 70 on the blood glucose curve of CGM, slightly decreased from 1.6 to 0.3 mg/dL (P = 0.08). The total number of basal insulin units decreased from 128 to 76, and that of bolus insulin decreased from 266 to 154; the dose of insulin could be markedly decreased. In addition, the mean 8-OHdG level decreased from 11.4 to 10.8 ng/mg Cre (P < 0.05), and the mean TNF-α level decreased from 2.31 to 1.79 pg/mL (P = 0.10). The mean adiponectin level increased from 5.01 to 5.53 μg/mL (P < 0.05). Canagliflozin improved blood glucose changes in type 2 diabetes using insulin. In addition, the results suggest its antioxidant actions. University Hospital Medical Information Network (UMIN no. 000019429).

Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial.

PubMed

Richie, John P; Das, Arun; Calcagnotto, Ana M; Sinha, Raghu; Neidig, Wanda; Liao, Jiangang; Lengerich, Eugene J; Berg, Arthur; Hartman, Terryl J; Ciccarella, Amy; Baker, Aaron; Kaag, Matthew G; Goodin, Susan; DiPaola, Robert S; El-Bayoumy, Karam

2014-08-01

Epidemiologic and laboratory studies indicate that dietary selenium protects against prostate cancer. Results from clinical trials suggest that selenium-enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing prostate cancer risk. Our objectives were to directly compare for the first time the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We performed a randomized double blind, placebo-controlled trial of SY (200 or 285 μg/day) and SeMet (200 μg/day) administered for 9 months in 69 healthy men. Primary endpoints included blood levels of selenium-containing compounds and oxidative stress biomarkers [urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) and blood glutathione (GSH)]. Secondary endpoints included plasma glucose and PSA levels. Compliance was high in all groups (>95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9 months in SeMet and low- and high-dose SY groups, respectively, and returned to baseline levels after a 3-month washout (P < 0.05). Levels of 8-OHdG and 8-iso-PGF2α were decreased 34% and 28%, respectively, after 9 months in the high-dose SY group (P < 0.05). These decreases were greatest in individuals with low baseline plasma levels of selenium (<127 ng/mL). No changes in serum PSA or blood glucose and GSH were observed. Overall, we showed for the first time, reductions in biomarkers of oxidative stress following supplementation with SY but not SeMet in healthy men. These findings suggest that selenium-containing compounds other than SeMet may account for the decrease in oxidative stress. ©2014 American Association for Cancer Research.

Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial

PubMed Central

Richie, John P.; Das, Arun; Calcagnotto, Ana M.; Sinha, Raghu; Neidig, Wanda; Liao, Jiangang; Lengerich, Eugene J.; Berg, Arthur; Hartman, Terryl J.; Ciccarella, Amy; Baker, Aaron; Kaag, Matthew G.; Goodin, Susan; DiPaola, Robert S.; El-Bayoumy, Karam

2014-01-01

Epidemiological and laboratory studies indicate that dietary selenium protects against prostate cancer. Results from clinical trials suggest that selenium-enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing prostate cancer risk. Our objectives were to directly compare for the first time the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We performed a randomized double blind, placebo-controlled trial of SY (200 or 285 µg/day) and SeMet (200 µg/day) administered for 9 months in 69 healthy men. Primary endpoints included blood levels of selenium-containing compounds and oxidative stress biomarkers (urine 8-hydroxy-2’-deoxyguanosine [8-OHdG] and 8-iso-prostaglandin-F2α [8-iso-PGF2α] and blood glutathione [GSH]). Secondary endpoints included plasma glucose and PSA levels. Compliance was high in all groups (>95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9 months in SeMet and low and high dose SY groups, respectively, and returned to baseline levels after a 3 month washout (P<0.05). Levels of 8-OHdG and 8-iso-PGF2α, were decreased 34% and 28%, respectively, after 9 months in the high dose SY group (P<0.05). These decreases were greatest in individuals with low baseline plasma levels of selenium (<127 ng/ml). No changes in serum PSA or blood glucose and GSH were observed. Overall, we showed for the first time, reductions in biomarkers of oxidative stress following supplementation with SY but not SeMet in healthy men. These findings suggest that selenium-containing compounds other than SeMet may account for the decrease in oxidative stress. PMID:24938534

Urinary fluoride levels and prevalence of dental fluorosis in three Brazilian cities with different fluoride concentrations in the drinking water.

PubMed

Heintze, S D; Bastos, J R; Bastos, R

1998-10-01

Urine samples from three daytime periods were collected from 545 5-50-year-old residents of three different Brazilian cities: Garça had fluoridated drinking water since 1973, Bauru since 1975 and Itápolis was not fluoridated. Dental fluorosis was examined in 985 5-24-year-olds using the Thylstrup-Fejerskov index (TF). The subjects were asked to estimate their daily intake of liquids and frequency of beverage consumption. The analysis of 94 water samples showed high variations in the fluoride content of the drinking water. The mean fluoride concentration of the water samples in Garça was 0.9 mg/L (range 0.75-1.2), in Bauru 0.64 mg/L (range 0.01-1.3), and in Itápolis 0.02 mg/L. Mean urinary fluoride concentration was 1.31 mg/L (s 0.61) in Garça, 0.88 mg/L (s 0.49) in Bauru, and 0.39 mg/L (s 0.21) in Itápolis. Self-reported daily liquid intake was not related to urinary fluoride concentration. The mean prevalence of fluorosis was 13.3% in Garça, 6.8% in Bauru, and 1.7% in Itápolis, with mainly categories TF 1 and TF 2 being recorded. Subjects with dental fluorosis tended to show a higher mean urinary fluoride concentration but the difference was not statistically significant. The study showed that fluoride exposure measured by urinary fluoride excretion was within the range expected for the level of fluoride concentration in the drinking water. However, enamel fluorosis tended to be markedly lower than expected. This study revealed that fluoride levels in the two cities with fluoridated drinking water were variable. To optimise anticaries benefits and minimise the risk of fluorosis greater control of the fluoride dosing of the drinking water is required.

Urinary bactericidal activity of single doses (250, 500, 750 and 1000 mg) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli.

PubMed

Stein, Gary E; Schooley, Sharon L; Nicolau, David P

2008-10-01

Increasing resistance to fluoroquinolones in uropathogens has become a clinical concern. The purpose of this study was to analyse the urinary bactericidal activity (UBA) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli. Ten healthy adult subjects (aged 23-60 years) received single doses of levofloxacin (250, 500, 750 and 1000 mg) and then blood and urine samples were collected in intervals (0-1.5, 1.5-4, 4-8, 8-12 and 12-24h) over 24h. Both serum and urine concentrations were measured by a validated high-performance liquid chromatography assay. Bactericidal titres in urine were determined against E. coli isolates with minimum inhibitory concentrations of 0.125, 4, 8, 16, 32 and 64microg/mL for levofloxacin. The mean serum pharmacokinetic parameters for these doses of levofloxacin were similar to previously published values. The mean peak urinary concentrations (0-1.5h) were 210, 347, 620 and 536microg/mL for the 250, 500, 750 and 1000 mg dose, respectively. Each dose of levofloxacin exhibited early (0-1.5h time period) bactericidal activity in urine in virtually all subjects against E. coli strains with MICs

[Comparative study of nanosized and microsized silicon dioxide on spermatogenesis function of male rats].

PubMed

Fan, Yi-Ou; Zhang, Ying-Hua; Zhang, Xiao-Peng; Liu, Bing; Ma, Yi-xin; Jin, Yi-he

2006-09-01

To compare the effects of nanosized and microsized silicon dioxide on spermatogenesis function of male rats exposed by inhalation. 45 male rats were randomly divided into control group and four experimental groups which were exposed by 100 mg/m3 or 300 mg/m3 nanosized and microsized silicon dioxide in inhalation chambers 2 hours every other day. Age-matched rats were exposed to room air with the same condition and served as controls. 65 days later, the testicular and epididymal viscera coefficients, the quantity and quality of sperm were examined and the histopathological assessment was done. The changes in biochemical parameters in serum and testes were also measured. Nanosized silicon dioxide could induce histopathological changes of testes in rats, and the effect was higher than that of microsized particles at the same concentration. Nanosized silicon dioxide could reduce the sperm counts of rats and the testicular LDH-C4 activities, increase MDA levels in the testes and the effect was higher than that of microsized particles at the same concentration. Nanosized silicon dioxide could lead to the reduction of sperm motility, testicular LDH-C4 activities and 8-hydroxydeoxyguanosine (8-OHdG) concentration in serum elevation in particles-exposed rats compared with the control animals, but there are no significant difference compared with that of microsized particles at the same concentration. The present findings suggest a different effect of impairment of sperm production and maturation induced by inhalation of nanosized and microsized silicon dioxide, and nanosized silicon dioxide exerted more severe reaction.

Integrated exposure assessment of sewage workers to genotoxicants: an urinary biomarker approach and oxidative stress evaluation

PubMed Central

2011-01-01

Background Sewage workers are exposed to multiple chemicals among which many are suspected genotoxicants. Therefore, they might incur DNA damage and oxidative stress. We aimed to explore integrated urinary biomarkers, assessing the overall urine genotoxicity by in vitro comet and micronucleus assays and measuring urinary 8-oxo-2'-deoxyguanosine. Methods During three consecutive working days, polycyclic aromatic hydrocarbons and volatile organic compounds were sampled in workplace air of 34 sewage and 30 office workers, as indicators of airborne exposure. The last day, subjects collected their 24 hours urine. Genotoxicity of urinary extracts was assessed by comet and micronucleus assays on a HepG2 cell line. Using competitive enzymatic immunoassay we evaluated the 24 hours urinary 8-oxo-2'-deoxyguanosine excretion. Benzo(a)pyrene toxicity equivalent factors and inhalation unit risk for Benzo(a)pyrene and benzene were used to give an estimate of cancer risk levels. Results Workplace air concentrations of polycyclic aromatic hydrocarbons (e.g. 23.7 [range 2.4-104.6] ng.m-3 for fluoranthene) and volatile organic compounds (e.g. 19.1 ± 2.9 [standard error] μ.m-3 for benzene) were elevated in sewage compared to office workplaces (P < 0.01) and corresponded to an increased lifetime cancer risk. The urinary extracts of sewage workers showed higher genotoxicity (P < 0.001) than office workers. Conclusions The integrated and non-specific urinary biomarkers of exposure showed that sewage workers experience exposure to mixtures of genotoxicants in the workplace. PMID:21435260

Integrated exposure assessment of sewage workers to genotoxicants: an urinary biomarker approach and oxidative stress evaluation.

PubMed

Al Zabadi, Hamzeh; Ferrari, Luc; Sari-Minodier, Irène; Kerautret, Marie-Aude; Tiberguent, Aziz; Paris, Christophe; Zmirou-Navier, Denis

2011-03-24

Sewage workers are exposed to multiple chemicals among which many are suspected genotoxicants. Therefore, they might incur DNA damage and oxidative stress. We aimed to explore integrated urinary biomarkers, assessing the overall urine genotoxicity by in vitro comet and micronucleus assays and measuring urinary 8-oxo-2'-deoxyguanosine. During three consecutive working days, polycyclic aromatic hydrocarbons and volatile organic compounds were sampled in workplace air of 34 sewage and 30 office workers, as indicators of airborne exposure. The last day, subjects collected their 24 hours urine. Genotoxicity of urinary extracts was assessed by comet and micronucleus assays on a HepG2 cell line. Using competitive enzymatic immunoassay we evaluated the 24 hours urinary 8-oxo-2'-deoxyguanosine excretion. Benzo(a)pyrene toxicity equivalent factors and inhalation unit risk for Benzo(a)pyrene and benzene were used to give an estimate of cancer risk levels. Workplace air concentrations of polycyclic aromatic hydrocarbons (e.g. 23.7 [range 2.4-104.6] ng.m-3 for fluoranthene) and volatile organic compounds (e.g. 19.1 ± 2.9 [standard error] μ.m-3 for benzene) were elevated in sewage compared to office workplaces (P < 0.01) and corresponded to an increased lifetime cancer risk. The urinary extracts of sewage workers showed higher genotoxicity (P < 0.001) than office workers. The integrated and non-specific urinary biomarkers of exposure showed that sewage workers experience exposure to mixtures of genotoxicants in the workplace.

[Role of hydrogen gas in regulating of poly (ADP-ribose) polymerase-1 dependent cell death in rat Schwann cells].

PubMed

Yu, Yang; Jiao, Yang; Li, Bo; Ma, Xiaoye; Yang, Tao; Xie, Keliang; Yu, Yonghao

2016-08-01

To investigate the protective effects and underlying molecular mechanisms of hydrogen (H2) on high glucose-induced poly (ADP-ribose) polymerase-1 (PARP-1) dependent cell death (PARthanatos) in primary rat Schwann cells. Cultured primary rat Schwann cells were randomly divided into five groups: blank control group (C group), H2 control group (H2 group), high osmotic control group (M group), high glucose treatment group (HG group), and H2 treatment group (HG+H2 group). The cells in H2 group and HG+H2 group were cultured with saturated hydrogen-rich medium containing 0.6 mmol/L of H2, and those in three control groups were cultured with low sugar DMEM medium containing 5.6 mmol/L of sugar, and the cells in HG and HG+H2 groups were given 44.4 mmol/L of glucose in addition (the medium containing 50 mmol/L of glucose), the cells in C group and H2 group were given the same volume of normal saline, and the cells in M group were given the same volume of mannitol. Cytotoxicity was evaluated using lactate dehydrogenase (LDH) release rate assays after treatment for 48 hours in each group. The contents of peroxynitrite (ONOO(-)) and 8-hydroxy-2-deoxyguanosine (8-OHdG) reflecting oxidative stress injury and DNA damage were detected by enzyme linked immunosorbent assay (ELISA). Poly (ADP-ribose) (PAR) protein expression was analyzed by Western Blot, and immunofluorescence staining was used to determine the nuclear translocation of the apoptosis-inducing factor (AIF). The cytotoxicity in HG and HG+H2 groups was significantly increased as compared with that of C group [LDH release rate: (61.40±2.89)%, (42.80±2.32)% vs. (9.92±0.38)%, both P < 0.01], the levels of ONOO(-) and 8-OHdG were markedly elevated [ONOO(-) (ng/L): 853.58±51.00, 553.11±38.66 vs. 113.56±14.22; 8-OHdG (ng/L): 1?177.37±60.97, 732.06±54.29 vs. 419.67±28.77, all P < 0.01], and the PAR protein expression was up-regulated (A value: 0.603±0.028, 0.441±0.010 vs. 0.324±0.021, both P < 0.01). The cytotoxicity, the levels of ONOO(-) and 8-OHdG, and PAR expression in HG+H2 group were significantly lower than those of the HG group (all P < 0.01). There were no significant differences in above parameters between H2 group as well as M group and C group. It was shown by immunofluorescence that AIF was expressed in the cytoplasm in C group, H2 group and M group, AIF was expressed in the whole cell in HG group, and the expression in the nucleus was particularly increased. A small amount of AIF expression was found in the nucleus of HG+H2 group, which indicated that high glucose could promote the AIF nuclear translocation, and that hydrogen-rich medium could prevent the process of translocation. High glucose levels could enhance DNA damage that enhance PARthanatos in primary rat Schwann cells. However, H2 can not only reduce DNA damage of injured cells, but also inhibit the special death process, reduce the cell toxicity, all of which have protective effects.

[Clinical evaluation of flomoxef in neonatal infections].

PubMed

Okura, K; Yamakawa, M; Kuroki, S; Haruta, T; Kobayashi, Y

1991-11-01

Serum concentrations, urinary excretion and clinical responses of flomoxef (FMOX) were studied. The results are summarized as follows. 1. Serum concentrations of FMOX were 17.4 micrograms/ml 1-hour after intravenous injection on the average in 5 cases who received approximately 10 mg/kg, 41.8 micrograms/ml in 2 cases given 20 mg/kg, and 69.6 micrograms/ml in 2 cases given 40 mg/kg, indicating that serum concentrations of FMOX changed in a dose-dependent manner in this range. Average serum half-life (T 1/2) in 4 mature babies was 2.48 hours and that in 6 premature babies was 3.17 hours, indicating that elimination rates in premature cases tend to be slower than those in mature cases. Urinary recovery rates averaged 39.2% in the first 6 hours in 5 cases examined. 2. Five newborns or premature babies received FMOX 33.1-80.2 mg/kg (b.i.d. or t.i.d.) via intravenous route for 5 to 8 days. FMOX showed excellent or good clinical effectiveness in the treatment of all patients including 1 case each of sepsis with urinary infection, furunclal otitis, impetigo, uterogenic fetus infection and urinary infection. Bacteriological responses were also studied, and eradication of identified organisms (Escherichia coli 3 strains and Staphylococcus aureus 2 strains) was obtained upon the FMOX treatment, but in 1 strain of S. aureus showed only a decrease. No adverse reactions were observed in any cases, but a slight elevation of eosinophil was noted in 1 patient receiving a dose of 210 mg a day. From the results obtained in these tests, FMOX appears to be very usefull and safe for the treatment of some infectious diseases in neonates.

Iodine status and thyroid function of Boston-area vegetarians and vegans.

PubMed

Leung, Angela M; Lamar, Andrew; He, Xuemei; Braverman, Lewis E; Pearce, Elizabeth N

2011-08-01

Adequate dietary iodine is required for normal thyroid function. The iodine status and thyroid function of U.S. vegetarians and vegans have not been previously studied. Environmental perchlorate and thiocyanate (inhibitors of thyroid iodine uptake) exposures may adversely affect thyroid function. The objective of the study was to assess the iodine status and thyroid function of U.S. vegetarians (consume plant based products, eggs, milk; abstain from meat, poultry, fish, shellfish) and vegans (avoid all animal products) and whether these may be affected by environmental perchlorate and thiocyanate exposures. This was a cross-sectional assessment of urinary iodine, perchlorate, and thiocyanate concentrations and serum thyroid function in Boston-area vegetarians and vegans. One hundred forty-one subjects (78 vegetarians, 63 vegans) were recruited; one vegan was excluded. Median urinary iodine concentration of vegans (78.5 μg/liter; range 6.8-964.7 μg/liter) was lower than vegetarians (147.0 μg/liter; range 9.3-778.6 μg/liter) (P < 0.01). Adjusted for cigarette smoking (confirmed by urinary cotinine levels) and thiocyanate-rich food consumption, median urinary thiocyanate concentration of vegans (630 μg/liter; range 108-3085 μg/liter) was higher than vegetarians (341 μg/liter; range 31-1963 μg/liter) (P < 0.01). There were no between-group differences in urinary perchlorate concentrations (P = 0.75), TSH (P = 0.46), and free T(4) (P = 0.77). Urinary iodine, perchlorate, and thiocyanate levels were not associated with TSH (P = 0.59) or free T(4) (P = 0.14), even when adjusted for multiple variables. U.S. vegetarians are iodine sufficient. U.S. vegans may be at risk for low iodine intake, and vegan women of child-bearing age should supplement with 150 μg iodine daily. Environmental perchlorate and thiocyanate exposures are not associated with thyroid dysfunction in these groups.

Iodine Status and Thyroid Function of Boston-Area Vegetarians and Vegans

PubMed Central

LaMar, Andrew; He, Xuemei; Braverman, Lewis E.; Pearce, Elizabeth N.

2011-01-01

Context: Adequate dietary iodine is required for normal thyroid function. The iodine status and thyroid function of U.S. vegetarians and vegans have not been previously studied. Environmental perchlorate and thiocyanate (inhibitors of thyroid iodine uptake) exposures may adversely affect thyroid function. Objective: The objective of the study was to assess the iodine status and thyroid function of U.S. vegetarians (consume plant based products, eggs, milk; abstain from meat, poultry, fish, shellfish) and vegans (avoid all animal products) and whether these may be affected by environmental perchlorate and thiocyanate exposures. Design and Setting: This was a cross-sectional assessment of urinary iodine, perchlorate, and thiocyanate concentrations and serum thyroid function in Boston-area vegetarians and vegans. Subjects: One hundred forty-one subjects (78 vegetarians, 63 vegans) were recruited; one vegan was excluded. Results: Median urinary iodine concentration of vegans (78.5 μg/liter; range 6.8–964.7 μg/liter) was lower than vegetarians (147.0 μg/liter; range 9.3–778.6 μg/liter) (P < 0.01). Adjusted for cigarette smoking (confirmed by urinary cotinine levels) and thiocyanate-rich food consumption, median urinary thiocyanate concentration of vegans (630 μg/liter; range 108-3085 μg/liter) was higher than vegetarians (341 μg/liter; range 31–1963 μg/liter) (P < 0.01). There were no between-group differences in urinary perchlorate concentrations (P = 0.75), TSH (P = 0.46), and free T4 (P = 0.77). Urinary iodine, perchlorate, and thiocyanate levels were not associated with TSH (P = 0.59) or free T4 (P = 0.14), even when adjusted for multiple variables. Conclusions: U.S. vegetarians are iodine sufficient. U.S. vegans may be at risk for low iodine intake, and vegan women of child-bearing age should supplement with 150 μg iodine daily. Environmental perchlorate and thiocyanate exposures are not associated with thyroid dysfunction in these groups. PMID:21613354

Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation.

PubMed

Chandurkar, Vikram; Shik, John; Randell, Edward

2008-01-01

To describe a patient with excess urinary thyroxine (T4) excretion and worsening of preexisting hypothyroidism in the setting of nephrotic syndrome and to determine whether excess urinary T4 excretion is present in other patients with proteinuria. We present data regarding the patient's initial presentation, diagnostic studies, and course of her illness. We suspected urinary T4 loss to be the cause of her presentation and analyzed her urine sample for total T4. We also analyzed differences in urinary T4 excretion in 22 patients with proteinuria and 16 control patients without proteinuria. Relevant medical literature is reviewed. A 44-year-old woman presented with a 3-month history of increasing fluid retention, weight gain, and fatigue. She had long-standing hypothyroidism on a stable levothyroxine dosage, 125 mcg/d. She had gained 27 kg and had developed significant edema. She had a grossly elevated thyroid-stimulating hormone level of 91 mIU/L. Her condition worsened, and a urinary protein measurement was 14.06 g/24 h-diagnostic of nephrotic syndrome. The levothyroxine dosage was increased to 225 mcg/d. Urinary total T4 concentration in a 24-hour sample was 59.0 microg/L (83.1 microg/24 h), indicating that a substantial fraction of her orally ingested T4 was lost in urine. Urinary total T4 excretion was significantly higher in patients with proteinuria (mean +/- standard deviation, 18.0 +/- 18.2 microg/L) vs control patients without proteinuria (mean, 3.8 +/- 1.8 microg/L) (P = .0014). In the patient described, urinary T4 loss due to proteinuria and nephrotic syndrome resulted in a severe exacerbation of underlying hypothyroidism.

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women.

PubMed

Horton, Megan K; Blount, Benjamin C; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

2015-11-01

Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4-0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Co-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

PubMed Central

Horton, Megan K.; Blount, Benjamin C.; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

2015-01-01

Background Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy. Objectives We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (± 2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results Individual analyte concentrations in urine were significantly correlated (Spearman’s r 0.4–0.5, p < 0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. PMID:26408806

Effects of an Exercise Intervention on Cancer-Related Fatigue and Its Relationship to Markers of Oxidative Stress.

PubMed

Repka, Chris P; Hayward, Reid

2018-06-01

Although the underlying mechanisms of cancer-related fatigue (CRF) are not fully characterized, treatment-associated oxidative stress may play a role. The purpose of this study was to determine the effect of an exercise intervention on the relationship between CRF and oxidative stress. Upon cessation of radiation or chemotherapy, 8 cancer patients participated in a 10-week exercise intervention (EX), while 7 continued standard care (CON). Blood draws and fatigue questionnaires were administered to cancer patients before and after the intervention as well as to 7 age-matched individuals with no cancer history. Changes in plasma 8-hydroxy-deoxyguanosine (8-OHdG), protein carbonyls, antioxidant capacity, and fatigue were compared between groups. Correlations between CRF and oxidative stress were evaluated. Mean total fatigue scores decreased significantly (5.0 ± 2.2 to 2.6 ± 1.5, P < .05) in EX, but not in CON. Antioxidant capacity significantly increased (+41%; P < .05) and protein carbonyls significantly decreased (-36%; P < .05) in EX, but not in CON. Increases in antioxidant capacity were significantly correlated with reductions in affective ( r = -.49), sensory ( r = -.47), and cognitive fatigue ( r = -.58). Changes in total ( r = .46) and affective ( r = .47) fatigue exhibited significant correlations with changes in 8-OHdG over time, while behavioral ( r = .46) and sensory ( r = .47) fatigue changes were significantly correlated with protein carbonyls. Oxidative stress may be implicated in CRF, while improved antioxidant capacity following an exercise intervention may play a role in mitigating CRF in cancer survivors.

DNA damage and antioxidants in treatment naïve children with obsessive-compulsive disorder.

PubMed

Şimşek, Şeref; Gençoğlan, Salih; Yüksel, Tuğba

2016-03-30

The current study aimed to investigate whether serum antioxidant levels and DNA damage differ between the children and adolescents with Obsessive Compulsive Disorder (OCD) and healthy controls. The study included 31 children (Male/Female, 22/9; age range 7-17 years), with treatment naïve OCD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) and 28 age- and gender-matched healthy control subjects. Children's Yale Brown Obsession Compulsion Scale (CY-BOC) was applied to the children. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-Hydroxy-2-Deoxyguanosine (8-OHdG) were all measured by the enzyme-linked immunosorbent assay method. GPx, CoQ and 8-OHdG levels were found to be significantly higher in the OCD group, compared to the control group (p=0.010, p=0.034, p=0.010, respectively); however, no significant difference was found in the SOD levels between two groups (p=0.10). There were no correlations between the CY-BOC scores, depression scores, duration of the disease and biochemical parameters (p>0.05, for all). Children with OCD were found to have higher antioxidant levels and oxidative DNA damage. The findings of this study support the role of oxidative stress in the pathogenesis of OCD. In this regard, any possible effect of adding antioxidants to conventional treatment can be investigated. Copyright © 2016. Published by Elsevier Ireland Ltd.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

PubMed Central

Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

2016-01-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo.

PubMed

Chen, Chiu-Lan; Chi, Chin-Wen; Liu, Tsung-Yun

2002-02-01

Chewing areca quid (AQ) has been implicated as a major risk factor for the development of oral squamous-cell carcinoma (OSCC). Recent studies have suggested that AQ-generated reactive oxygen species (ROS) is one of the contributing factors for oral carcinogenesis. However, the AQ used in Taiwan is different from that used in other countries. This study is designed to test whether ROS are generated and the consequent effects in locally prepared AQ in vivo. We measured the hydroxyl radical formation, as represented by the presence of o- and m-tyrosine in saliva from volunteers who chewed AQ containing 20 mg phenylalanine. Their saliva contained significantly higher amounts (p < .05) of o- and m-tyrosine as compared to the controls. In addition, chewing AQ containing Piper betle inflorescence generated higher amounts of m-tyrosine, but not o-tyrosine, in saliva than did chewing AQ containing betel leaf. We further tested the oxidative DNA damaging effect of the reconstituted AQ, as evidenced by the elevation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, in hamster buccal pouch. Following daily painting for 14 d, the 8-OH-dG level in hamster buccal pouch is significantly elevated (p < .05) in the AQ-treated group versus the controls. These findings demonstrate that ROS, such as hydroxyl radical, are formed in the human oral cavity during AQ chewing, and chewing such prepared AQ might cause oxidative DNA damage to the surrounding tissues.

The effect of nandrolone treatment with and without enforced swimming on histological and biochemical changes in the heart and coronary artery of male rats

PubMed Central

Tofighi, Asghar; Shirpoor, Minoo; Ansari, Mohammad Hasan Khadem; Shirpoor, Alireza; Zerehpoosh, Mitra

2017-01-01

Objective: Chronic anabolic androgenic steroid (AAS) consumption increases incidence of cardiovascular abnormalities in athletes and mechanisms underlying those abnormalities continue to be investigated. This study examines whether nandrolone consumption induced cardiac and coronary artery wall abnormalities via oxidative stress. It was also designed to determine whether enforced swimming augmented possible cardiotoxic effects of nandrolone in rat heart. Methods: Twenty-four male Wistar rats were divided into 3 groups: control, nandrolone, and nandrolone with enforced swimming. Nandrolone group received 10 mg/kg body weight nandrolone 3 times a week for 6 weeks. Nandrolone group with enforced swimming received the same amount of nandrolone and was forced to swim with excess weight of 20% body weight. Results: After 6 weeks of treatment, results indicated proliferation of heart muscle and coronary smooth muscle cells and lipid peroxidation; significant rise in levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), nicotinamide adenine dinucleotide phosphate oxidase, homocysteine (Hcy), apolipoprotein B, low-density lipoprotein, and cholesterol, as well as severe fibrosis in heart tissue and around coronary arteries of nandrolone and nandrolone with enforced swimming groups compared with control group. Conclusion: These findings strongly support idea that nandrolone intake by sedentary rats and exercised rats induced heart abnormality mediated by oxidative stress, which was manifest in increased lipid peroxidation, Hcy, and 8-OHdG in heart tissue. PMID:27752030

Polycarbonate Bottle Use and Urinary Bisphenol A Concentrations

PubMed Central

Carwile, Jenny L.; Luu, Henry T.; Bassett, Laura S.; Driscoll, Daniel A.; Yuan, Caterina; Chang, Jennifer Y.; Ye, Xiaoyun; Calafat, Antonia M.; Michels, Karin B.

2009-01-01

Background Bisphenol A (BPA) is a high-production-volume chemical commonly used in the manufacture of polycarbonate plastic. Low-level concentrations of BPA in animals and possibly in humans may cause endocrine disruption. Whether ingestion of food or beverages from polycarbonate containers increases BPA concentrations in humans has not been studied. Objectives We examined the association between use of polycarbonate beverage containers and urinary BPA concentrations in humans. Methods We conducted a nonrandomized intervention of 77 Harvard College students to compare urinary BPA concentrations collected after a washout phase of 1 week to those taken after an intervention week during which most cold beverages were consumed from polycarbonate drinking bottles. Paired t-tests were used to assess the difference in urinary BPA concentrations before and after polycarbonate bottle use. Results The geometric mean urinary BPA concentration at the end of the washout phase was 1.2 μg/g creatinine, increasing to 2.0 μg/g creatinine after 1 week of polycarbonate bottle use. Urinary BPA concentrations increased by 69% after use of polycarbonate bottles (p < 0.0001). The association was stronger among participants who reported ≥ 90% compliance (77% increase; p < 0.0001) than among those reporting < 90% compliance (55% increase; p = 0.03), but this difference was not statistically significant (p = 0.54). Conclusions One week of polycarbonate bottle use increased urinary BPA concentrations by two-thirds. Regular consumption of cold beverages from polycarbonate bottles is associated with a substantial increase in urinary BPA concentrations irrespective of exposure to BPA from other sources. PMID:19750099

Bitumen workers handling mastic versus rolled asphalt in a tunnel: assessment of exposure and biomarkers of irritation and genotoxicity.

PubMed

Raulf-Heimsoth, Monika; Marczynski, Boleslaw; Spickenheuer, Anne; Pesch, Beate; Welge, Peter; Rühl, Reinhold; Bramer, Rainer; Kendzia, Benjamin; Heinze, Evelyn; Angerer, Jürgen; Brüning, Thomas

2011-06-01

Emission levels of vapours and aerosols of bitumen are different when processing rolled asphalt compared to mastic asphalt, with working temperatures up to 180 and 250°C, respectively. During the Human Bitumen Study, we examined six workers handling rolled asphalt and mastic asphalt in two consecutive weeks at the same construction site in a tunnel. In addition to the determination of exposure to bitumen and polycyclic aromatic hydrocarbons (PAH) during shift, we examined urinary PAH metabolites, irritative and genotoxic effects before and after shift. Median personal shift concentration of vapours and aerosols of bitumen was 1.8 (range 0.9-2.4) mg/m(3) during the application of rolled asphalt and 7.9 (range 4.9-11.9) mg/m(3) when mastic asphalt was applied. Area measurement of vapours and aerosols of bitumen revealed higher concentrations than the personal measurements for mastic asphalt (mastic asphalt: 34.9 mg/m(3); rolled asphalt: 1.8 mg/m(3)). Processing mastic asphalt was associated also with higher PAH concentrations. Urinary 1-hydroxypyrene and the sum of 1-, 2+ 9-, 3- and 4-hydroxyphenanthrene increased slightly during shift without clear difference between mastic and rolled asphalt application. However, the post-shift urinary PAH-metabolite concentrations did not reflect the different PAH exposure during mastic and rolled asphalt application. Individual workers could be identified by their spirometry results indicating that these data reflect more chronic than acute effects. In most cases, an increase of 8-oxodGuo adducts was observed during shift that was independent of the asphalt application. 8-oxodGuo and (+)-anti-BPDE-DNA adducts were higher than in exposed workers of the Human Bitumen Study independent of the asphalt application. The DNA-strand breaks were considerably higher pre-shift and decreased during shift. In this study, mastic asphalt application led to significantly higher exposure to vapours and aerosols of bitumen, as well as to airborne PAH, compared to rolled asphalt application. Nevertheless, no differences in the excretion of urinary PAH metabolites, lung function impairment and genotoxic markers were detected. However, higher levels of genotoxicity markers on both examination days compared with the results of the Human Bitumen Study may indicate a possible influence of the specific tunnel setting.

Urine and toenail cadmium levels in pregnant women: A reliability study.

PubMed

White, Alexandra J; O'Brien, Katie M; Jackson, Brian P; Karagas, Margaret R

2018-05-29

Cadmium, as measured in human tissue, has been associated with numerous health outcomes. However, few studies have evaluated the reliability of cadmium measurements across different biologic samples. We evaluated toenail cadmium levels over time and compared toenail cadmium to urinary cadmium. We also evaluated the relationship between biomarker concentrations and cigarette smoking, a known source of cadmium exposure. Cadmium was assessed in urine and toenail samples collected from 1338 pregnant women participating in the New Hampshire Birth Cohort Study. Each participant was asked to provide a urine and a toenail sample at enrollment (between 24 and 28 weeks gestation) and another toenail sample 2-8 weeks postpartum. Cadmium concentrations were determined using inductively-coupled plasma mass spectrometry. Spearman correlations were assessed for cadmium in the toenails across the two-time points and comparing toenail and urine levels. Smoking status was evaluated as a predictor of cadmium levels. Toenail cadmium assessed during pregnancy and postpartum were modestly correlated (R = 0.3, p < 0.0001). However, urine and toenail cadmium levels were unrelated (R = -0.03, p = 0.46). Both toenail and urinary cadmium levels were associated with women's smoking status. Our findings suggest that both toenail and urinary cadmium concentrations reflect the major source of exposure - cigarette smoking. Toenail cadmium concentrations are modestly reproducible pre- and postpartum; but do not appear to be related to urinary cadmium and thus likely represent different windows and chronicity of exposure among pregnant women. Published by Elsevier Ltd.

Urinary leukotriene E4 concentrations as a potential marker of inflammation in dogs with inflammatory bowel disease.

PubMed

Im Hof, M; Schnyder, M; Hartnack, S; Stanke-Labesque, F; Luckschander, N; Burgener, I A

2012-01-01

Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are chronic enteropathies of dogs (CCE) that currently can only be differentiated by their response to treatment after exclusion of other diseases. In humans, increased urinary concentrations of leukotriene E4 (LTE4) have been associated with active IBD. To evaluate urinary LTE4 concentrations in dogs with IBD, FRD, and healthy controls, and to assess correlation of urinary LTE4 concentrations with the canine IBD activity index (CIBDAI) scores. Eighteen dogs with IBD, 19 dogs with FRD, and 23 healthy control dogs. In this prospective study, urine was collected and CIBDAI scores were calculated in client-owned dogs with IBD and those with FRD. Quantification of LTE4 in urine was performed by liquid chromatography-tandem mass spectrometry and corrected to creatinine. Urinary LTE4 concentrations were highest in dogs with IBD (median 85.2 pg/mg creatinine [10th-90th percentiles 10.9-372.6]) followed by those with FRD (median 31.2 pg/mg creatinine [10th-90th percentiles 6.2-114.5]) and control dogs (median 21.1 pg/mg creatinine [10th-90th percentiles 9.1-86.5]). Urinary LTE4 concentrations were higher in dogs with IBD than in control dogs (P = .011), but no significant difference between IBD and FRD was found. No correlation was found between urinary LTE4 concentrations and CIBDAI. The higher urinary LTE4 concentrations in dogs with IBD suggest that cysteinyl leukotriene pathway activation might be a component of the inflammatory process in canine IBD. Furthermore, urinary LTE4 concentrations are of potential use as a marker of inflammation in dogs with CCE. Copyright © 2012 by the American College of Veterinary Internal Medicine.

The consumption of canned food and beverages and urinary Bisphenol A concentrations in NHANES 2003-2008.

PubMed

Hartle, Jennifer C; Navas-Acien, Ana; Lawrence, Robert S

2016-10-01

Exposure to Bisphenol A (BPA) is ubiquitous and includes dietary and environmental pathways. BPA is rapidly glucuronidated in the body, and both BPA and its conjugates can be readily measured in urine. To investigate the contribution of canned food and beverages, known sources of BPA contamination, to BPA biomarkers of exposure using dietary and urinary BPA concentration information in a representative sample of the U.S. We evaluated 7669 NHANES 2003-2008 participants 6 years and older with 24-h dietary recall information and urinary BPA concentrations available. Using linear regression models, we evaluated the associations between recent canned food and beverage consumption and urinary BPA concentrations, adjusting for potential confounders. We found 9% of our participants consumed one canned food in the past 24h and 2% consumed two or more canned foods. The consumption of one canned food vs. none was associated with 24% (95% CI 1.11, 1.38) higher urinary BPA concentrations. The consumption of two or more canned foods vs. none was associated with 54% (95% CI 1.27, 1.88) higher urinary BPA concentrations. The consumption of one or more of some specific types of canned foods vs. none were associated with higher urinary BPA concentrations: 41% (95% CI 1.23, 1.63) higher BPA for vegetable and fruit, 70% (95% CI 1.18, 2.44) higher for canned pasta, and 229% (95% CI 1.22, 4.30) higher for canned soup. Canned beverages were not associated with urinary BPA concentrations. Canned food, including some specific types such as canned vegetable and fruit, canned pasta, and canned soup were associated with higher levels of urinary BPA concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

The consumption of canned food and beverages and urinary Bisphenol A concentrations in NHANES 2003–2008

PubMed Central

Hartle, Jennifer C.; Navas-Acien; Lawrence, Robert S.

2016-01-01

Background Exposure to Bisphenol A (BPA) is ubiquitous and includes dietary and environmental pathways. BPA is rapidly glucuronidated in the body, and both BPA and its conjugates can be readily measured in urine. Objectives To investigate the contribution of canned food and beverages, known sources of BPA contamination, to BPA biomarkers of exposure using dietary and urinary BPA concentration information in a representative sample of the U.S. population. Methods We evaluated 7,669 NHANES 2003–2008 participants 6 years and older with 24-hour dietary recall information and urinary BPA concentrations available. Using linear regression models, we evaluated the associations between recent canned food and beverage consumption and urinary BPA concentrations, adjusting for potential confounders. Results We found 9% of our participants consumed one canned food in the past 24 hours and 2% consumed two or more canned foods. The consumption of one canned food vs. none was associated with 24% (95% CI 1.11, 1.38) higher urinary BPA concentrations. The consumption of two or more canned foods vs. none was associated with 54% (95% CI 1.27, 1.88) higher urinary BPA concentrations. The consumption of one or more of some specific types of canned foods vs. none were associated with higher urinary BPA concentrations: 41% (95% CI 1.23, 1.63) higher BPA for vegetable and fruit, 70% (95% CI 1.18, 2.44) higher for canned pasta, and 229% (95% CI 1.22, 4.30) higher for canned soup. Canned beverages were not associated with urinary BPA concentrations. Conclusions Canned food, including some specific types such as canned vegetable and fruit, canned pasta, and canned soup were associated with higher levels of urinary BPA concentrations. PMID:27362993

Gender and age differences in mixed metal exposure and urinary excretion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berglund, Marika, E-mail: Marika.Berglund@ki.se; Lindberg, Anna-Lena; Rahman, Mahfuzar

Background: Little is known about the variation in exposure to toxic metals by age and gender and other potential modifying factors. We evaluated age and gender differences by measurements of metal/element concentrations in urine in a rural population in Matlab, Bangladesh, in three age groups: 8-12 (N=238), 14-15 (N=107) and 30-88 (N=710) years of age, living in an area with no point sources of metal exposure but where elevated water arsenic concentrations are prevalent. Results: We found marked differences in urine concentrations of metals and trace elements by gender, age, tobacco use, socioeconomic and nutritional status. Besides a clearly elevatedmore » urinary arsenic concentration in all age groups (medians 63-85 {mu}g As/L), and despite the low degree of contamination from industries and traffic, the urine concentrations of toxic metals such as cadmium and lead were clearly elevated, especially in children (median 0.31 {mu}g Cd/L and 2.9 {mu}g Pb/L, respectively). In general, women had higher urinary concentrations of toxic metals, especially Cd (median 0.81 {mu}g/L) compared to men (0.66 {mu}g/L) and U (median 10 ng/L in women, compared to 6.4 ng/L in men), while men had higher urinary concentrations of the basic and essential elements Ca (69 mg/L in men, 30-50 years, compared to 52 mg/L in women), Mg (58 mg/L in men compared to 50 mg/L in women), Zn (182 {mu}g/L in men compared to 117 {mu}g/L in women) and Se (9.9 {mu}g/L in men compared to 8.7 {mu}g/L in women). Manganese was consistently higher in females than in males in all age groups, suggesting a biological difference between females and males in Mn metabolism. Increasing socioeconomic status decreased the toxic metal exposure significantly in children and especially in men. Poor iron status was detected in 17% of children, adolescents and women, but only in 6% of men. Also zinc deficiency was more prevalent in females than in males. Conclusions: Women and children seemed to be more at risk for toxic metal exposure than men and at the same time more vulnerable to micronutrient deficiency. Higher concentrations of the toxic metals in urine in women are likely to reflect an increased gastrointestinal absorption of these metals at micronutrient deficiency, such as low body iron stores and Zn deficiency. Higher urinary concentrations of the essential elements in men likely reflect a better nutritional status. There is a need for information on exposure, lifestyle and socioeconomic factors, stratified by gender and age, for the purpose of conducting balanced risk assessment and management that considers such differences.« less

Effect of feeding sweet-potato condensed distillers solubles on intake and urinary excretion of minerals in Japanese Black steers.

PubMed

Kamiya, Yuko; Kamiya, Misturu; Hattori, Ikuo; Hayashi, Yoshiro; Funaba, Masayuki; Matsui, Tohru

2017-01-01

Four Japanese Black steers (16 months of age) were assigned to a 4 × 4 Latin square design to investigate the effect of graded levels of sweet-potato condensed distillers solubles (SCDS) in their diets on intake and urinary excretion of minerals. The four diets consisted of 0%, 10%, 20% and 30% (dry matter (DM) basis) SCDS, with SCDS replacing commercial concentrate (CC). Intake of K, Cl, S, P and Mg increased linearly with increasing SCDS content. Urinary pH increased linearly with increasing dietary SCDS content. SCDS feeding increased urinary K concentrations (linear and quadratic effects). Urinary concentrations of Cl increased linearly with increasing SCDS content. In contrast, urinary concentrations of Mg decreased with increasing SCDS content. Feeding of SCDS did not apparently affect urinary NH 3 ,P, Na or Ca concentrations. These results suggest that high SCDS feeding is not a risk for crystallization of minerals leading to the formation of magnesium-phosphate type calculi: although SCDS contains large amounts of P and Mg, high SCDS feeding decreased the Mg concentration and did not affect the P concentration in urine. Additionally, high SCDS feeding had no apparent effects on plasma concentrations of Na, K, Cl, Ca or inorganic P. © 2016 Japanese Society of Animal Science.

Speciation of arsenic in exfoliated urinary bladder epithelial cells from individuals exposed to arsenic in drinking water.

PubMed

Hernández-Zavala, Araceli; Valenzuela, Olga L; Matousek, Tomás; Drobná, Zuzana; Dĕdina, Jirí; García-Vargas, Gonzalo G; Thomas, David J; Del Razo, Luz M; Stýblo, Miroslav

2008-12-01

The concentration of arsenic in urine has been used as a marker of exposure to inorganic As (iAs). Relative proportions of urinary metabolites of iAs have been identified as potential biomarkers of susceptibility to iAs toxicity. However, the adverse effects of iAs exposure are ultimately determined by the concentrations of iAs metabolites in target tissues. In this study we examined the feasibility of analyzing As species in cells that originate in the urinary bladder, a target organ for As-induced cancer in humans. Exfoliated bladder epithelial cells (BECs) were collected from urine of 21 residents of Zimapan, Mexico, who were exposed to iAs in drinking water. We determined concentrations of iAs, methyl-As (MAs), and dimethyl-As (DMAs) in urine using conventional hydride generation-cryotrapping-atomic absorption spectrometry (HG-CT-AAS). We used an optimized HG-CT-AAS technique with detection limits of 12-17 pg As for analysis of As species in BECs. All urine samples and 20 of 21 BEC samples contained detectable concentrations of iAs, MAs, and DMAs. Sums of concentrations of these As species in BECs ranged from 0.18 to 11.4 ng As/mg protein and in urine from 4.8 to 1,947 ng As/mL. We found no correlations between the concentrations or ratios of As species in BECs and in urine. These results suggest that urinary levels of iAs metabolites do not necessarily reflect levels of these metabolites in the bladder epithelium. Thus, analysis of As species in BECs may provide a more effective tool for risk assessment of bladder cancer and other urothelial diseases associated with exposures to iAs.

Renal and Glycemic Effects of High-Dose Chromium Picolinate in db/db Mice: Assessment of DNA Damage

PubMed Central

Mozaffari, Mahmood S.; Baban, Babak; Abdelsayed, Rafik; Liu, Jun Yao; Wimborne, Hereward; Rodriguez, Nancy; Abebe, Worku

2011-01-01

This study examined renal and glycemic effects of chromium picolinate (Cr(pic)3) supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end (AGE) products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (8-OHdG, an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower while blood pressure was similar between untreated db/db mice and their db/m controls. High Cr(pic)3 intake (i.e., 100 mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100 mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control and it causes moderate reduction in albuminuria, without affecting histopathological appearance of the kidney and increasing the risk for DNA damage. PMID:21959055

Impact of prenatal exposure to cadmium on cognitive development at preschool age and the importance of selenium and iodine.

PubMed

Kippler, Maria; Bottai, Matteo; Georgiou, Vaggelis; Koutra, Katerina; Chalkiadaki, Georgia; Kampouri, Mariza; Kyriklaki, Andriani; Vafeiadi, Marina; Fthenou, Eleni; Vassilaki, Maria; Kogevinas, Manolis; Vahter, Marie; Chatzi, Leda

2016-11-01

The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.

Parabens in 24 h urine samples of the German Environmental Specimen Bank from 1995 to 2012.

PubMed

Moos, Rebecca K; Koch, Holger M; Angerer, Jürgen; Apel, Petra; Schröter-Kermani, Christa; Brüning, Thomas; Kolossa-Gehring, Marike

2015-10-01

Parabens are widely used as antimicrobial preservatives in personal care and consumer products, food and pharmaceuticals. Due to their ubiquity, humans are constantly exposed to these chemicals. We assessed exposure to nine parabens (methyl-, ethyl-, n- and iso-propyl-, n- and iso-butyl-, benzyl-, pentyl- and heptyl paraben) in the German population from 1995 to 2012 based on 660 24h urine samples from the German Environmental Specimen Bank (ESB) using on-line HPLC coupled to isotope dilution tandem mass spectrometry. The limit of quantification (LOQ) was 0.5 μg/L for all parabens. We detected methyl-, ethyl- and n-propyl paraben in 79-99% of samples, followed by n-butyl paraben in 40% of samples. We infrequently detected iso-butyl-, iso-propyl- and benzyl paraben in 24%, 4% and 1.4% of samples, respectively. Urinary concentrations were highest for methyl paraben (median 39.8 μg/L; 95th percentile 319 μg/L) followed by n-propyl paraben (4.8 μg/L; 95th percentile 74.0 μg/L) and ethyl paraben (2.1 μg/L; 95th percentile 39.1 μg/L). Women had significantly higher urinary levels for all parabens than men, except for benzyl paraben. Samples from the ESB revealed that over the investigation period of nearly 20 years urinary paraben levels remained surprisingly constant; only methyl paraben had a significant increase, for both men and women. We found strong correlations between methyl- and n-propyl paraben and between n- and iso-butyl paraben. These results indicate that parabens are used in combination and arise from common sources of exposure. Urinary excretion factors are needed to extrapolate from individual urinary concentrations to actual doses. Copyright © 2015 Elsevier GmbH. All rights reserved.

Daily urinary urea excretion to guide intermittent hemodialysis weaning in critically ill patients.

PubMed

Aniort, Julien; Ait Hssain, Ali; Pereira, Bruno; Coupez, Elisabeth; Pioche, Pierre Antoine; Leroy, Christophe; Heng, Anne Elisabeth; Souweine, Bertrand; Lautrette, Alexandre

2016-02-19

There are no easily available markers of renal recovery to guide intermittent hemodialysis (IHD) weaning. The aim of this study was to identify markers for IHD weaning in critically ill patients with acute kidney injury (AKI). We performed a retrospective single-center cohort study of patients treated with IHD for at least 7 days and four dialysis sessions for AKI between 2006 and 2011 in an intensive care unit (ICU) of a French university hospital. Blood and urinary markers were recorded on the day of the last IHD in the ICU for unweaned patients and 2 days after the last IHD for weaned patients. Factors associated with IHD weaning were identified by multiple logistic regression. The areas under the receiver operating characteristic curve (AUROC) and the characteristics of the best diagnostic thresholds were compared. Sixty-seven patients were analyzed, including thirty-seven IHD-weaned patients. Urine output [odds ratio (OR) 1.59, 95% confidence interval (CI) 1.20-2.10 (per ml/kg/24 h increase); P = 0.01] and urinary urea concentration [OR 1.29, 95% CI 1.01-1.64 (per 10 mmol/L increase); P = 0.04] were both associated with IHD weaning. The optimal diagnostic thresholds for IHD weaning were urine output greater than 8.5 ml/kg/24 h, urinary urea concentration greater than 148 mmol/L, and daily urea excretion greater than 1.35 mmol/kg/24 h, with accuracy of 82.1%, 76.1%, and 92.5% (P = 0.03), respectively. The AUROC of daily urinary urea excretion (0.96) was greater than the AUROC of urine output (0.86) or the AUROC of urinary urea concentration (0.83) (P < 0.001). A daily urinary urea excretion greater than 1.35 mmol/kg/24 h was found to be the best marker for weaning ICU patients with AKI from IHD.

Cypermethrin toxication leads to histopathological lesions and induces inflammation and apoptosis in common carp (Cyprinus carpio L.).

PubMed

Arslan, Harun; Özdemir, Selçuk; Altun, Serdar

2017-08-01

Cypermethrin (Cyp), a known neurotoxic pesticide, is widely used in agricultural applications. In the present study, the aim was to determine the histopathological effects of Cyp toxication and evaluate the activation of inducible nitric oxide synthetase (iNOS) and 8-hydroxy-2-deoxyguanosine (8-OHdG) using an immunofluorescence assay. Thereafter, we identified the expressions of caspase 3, capsase 8, iNOS, and metallothionein 1 (MT1) genes in common carp using quantitative reverse transcription polymerase chain reaction (qRT-PCR). High and low doses of Cyp were administered to experimental groups for 24, 48, 72, and 96 h. As a result, necrotic neurons in different stages and desquamation of ependymal cells due to necrosis were detected in the brain. Histopathological changes, including hyperplasia of lamellar cells, telangiectasia of lamellae and thickening due to cellular infiltration in gills, hemorrhage, diffuse hydropic degeneration, and focal necrosis in the liver were observed in the experimental groups. Immunopositive reactions of 8-OHdG were clearly observed in the nuclei and cytoplasm of neurons, and positive reactions for iNOS were detected in the cytoplasm of neurons and in the glial cells of the experimental groups. Furthermore, we found that caspase 3, capsase 8, iNOS, and MT1 genes were up-regulated in the brain when exposed to both high and low doses of Cyp. In conclusion, our findings revealed that Cyp toxication harms the organs of common carp, particularly the brain, and also gives rise to inflammation, DNA damage, and apoptosis. Therefore, the use of Cyp should be restricted to protect the health of aquatic animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of exercise on markers of oxidative stress: an Ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention Trial

PubMed Central

Friedenreich, Christine M; Pialoux, Vincent; Wang, Qinggang; Shaw, Eileen; Brenner, Darren R; Waltz, Xavier; Conroy, Shannon M; Johnson, Rhys; Woolcott, Christy G; Poulin, Marc J; Courneya, Kerry S

2016-01-01

Background Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women. Methods The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50–74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed. Results In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity. Conclusions A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women. Trial registration number NCT00522262. PMID:27900199

Urinary nicotine concentrations in cigarette and pipe smokers.

PubMed Central

Wald, N J; Idle, M; Boreham, J; Bailey, A; Van Vunakis, H

1984-01-01

Urinary concentrations of nicotine were studied in men who did not smoke (27) and in men who smoked cigarettes only (145) or pipes only (48). The median urinary nicotine concentrations were less than 50 ng/ml (the detection limit of the assay for urine tests) in the non-smokers, 1393 ng/ml in the cigarette smokers, and 1048 ng/ml in the pipe smokers. These values were standardised for urinary pH and creatinine concentration to allow for the fact that nicotine excretion is influenced by the acidity of the urine and by urinary flow rate. The high urinary nicotine concentrations in the pipe and cigarette smokers indicated that both types of smoker have relatively high systemic nicotine concentrations. This observation, together with the fact that large prospective studies have shown that pipe smokers have no material excess risk of coronary heart disease whereas cigarette smokers do, provides evidence that nicotine is unlikely to be the major cause of the excess deaths from coronary heart disease in cigarette smokers. This conclusion is consistent with earlier observations based on serum cotinine concentrations in smokers and non-smokers. PMID:6740539

Evolution of urinary iodine excretion over eleven years in an adult population.

PubMed

Gutiérrez-Repiso, Carolina; Colomo, Natalia; Rojo-Martinez, Gemma; Valdés, Sergio; Tapia, Maria J; Esteva, Isabel; Ruiz de Adana, Maria S; Rubio-Martin, Elehazara; Lago-Sampedro, Ana; Santiago, Piedad; Velasco, Ines; Garcia-Fuentes, Eduardo; Moreno, Jose C; Soriguer, Federico

2015-08-01

Few prospective cohort studies have evaluated dietary iodine intake and urinary iodine concentrations in the general adult population. We assess the evolution of urinary iodine excretion and factors that may influence it in an adult population followed for 11 years. A population-based cohort study was undertaken in Pizarra (Spain). In the three study phases (baseline (n = 886), and 6 (n = 788) and 11 years later (n = 501)), participants underwent an interview and a standardized clinical examination that included a food questionnaire, and thyroid hormone and urinary iodine determinations. Subjects with thyroid dysfunction, palpable goiter or urinary iodine excretion >400 μg/L were excluded. Urinary iodine increased over the years (100.6 ± 70.0 μg/L at baseline vs. 125.4 ± 95.2 μg/L at 6 years and 141.6 ± 81.4 μg/L at 11 years; p < 0.0001). Urinary iodine was significantly higher in subjects who reported iodized salt consumption and in subjects with a higher intake of dairy products (p < 0.05). Consumption of iodized salt (Risk ratio (RR) = 1.23, 95% CI [1.01-2.05]) and dairy products (RR = 2.07, 95% CI [1.01-4.23]), and a baseline urinary iodine concentration ≥100 μg/L (RR = 1.26, 95% CI [1.04-1.53]) were significantly associated with urinary iodine concentrations ≥100 μg/L at 11 years. There is no correlation between thyroid function (TSH, free triiodothyronine or free thyroxine levels) and urinary iodine concentrations in conditions of iodine sufficiency. The increase in urinary iodine concentrations over eleven years is associated with an increase in iodized salt intake and with the dairy products intake, and possibly with a higher iodine content of dairy products. However, individual variability in urinary iodine excretion was not fully explained by dietary iodine intake alone; previous urinary iodine concentrations were also important. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Simultaneous quantification of cortisol and cortisone in urines from infants with packed-fiber solid-phase extraction coupled to HPLC-MS/MS.

PubMed

Li, Chen; Zhang, Zhao; Liu, Xiongwei; Shen, Kangwei; Gu, Pan; Kang, Xuejun

2017-09-01

Cortisol and cortisone are two important glucocorticoids in human body, their interconversion is controlled by two isotypes of 11β-hydroxy steroid dehydrogenase (11β-HSD1 and 11β-HSD2). The ratio of urinary cortisol to cortisone can be used to assess the activity of 11β-HSDs. An analytical method to quantify urinary cortisol and cortisone using high performance liquid chromatographic tandem mass spectrometry following a packed-fiber solid-phase extraction (PFSPE) was developed. The proposed method was validated and applied to determine the urinary cortisol and cortisone concentrations in infants. Linearity was observed in the range of 0.6-150ng/mL for cortisol and 0.8-200ng/mL for cortisone. The intra-day RSD was 2.4-4.5% for cortisol and 3.3-6.2% for cortisone. Inter-day RSD was 3.7-6.6% for cortisol and 4.3-8.2% for cortisone. The recovery was 97.8±4.6% for cortisol and 98.9±4.4% for cortisone. The established method is simple and efficient for the quantification of urinary cortisol and cortisone and for indirectly assessing the activity of 11β-hydroxy steroid dehydrogenase. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Concentrated Apple Extract on Experimental Colitis Induced by Acetic Acid.

PubMed

Pastrelo, Maurício Mercaldi; Dias Ribeiro, Carla Caroline; Duarte, Joselmo Willamys; Bioago Gollücke, Andréa Pitelli; Artigiani-Neto, Ricardo; Ribeiro, Daniel Araki; Miszputen, Sender Jankiel; Fujiyama Oshima, Celina Tizuko; Ribeiro Paiotti, Ana Paula

2017-01-01

Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1-Sham/saline solution, G2-CAE/control, G3-acetic acid/control, G4-curative- CAE treatment and G5-preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

Maternal Urinary Triclosan Concentration in Relation to Maternal and Neonatal Thyroid Hormone Levels: A Prospective Study.

PubMed

Wang, Xu; Ouyang, Fengxiu; Feng, Liping; Wang, Xia; Liu, Zhiwei; Zhang, Jun

2017-06-27

Triclosan (TCS) is a synthetic antibacterial chemical widely used in personal care products. TCS exposure has been associated with decreased thyroid hormone levels in animals, but human studies are scarce and controversial. We evaluated the association between maternal TCS exposure and thyroid hormone levels of mothers and newborns. TCS was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in urine samples collected during gestational weeks 38.8±1.1 from 398 pregnant women in a prospective birth cohort enrolled in 2012-2013 in Shanghai, China. Maternal serum levels of free thyroxine (FT 4 ), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were obtained from medical records. Cord blood levels of free triiodothyronine (FT 3 ), FT 4 , TSH, and TPOAb were measured. Multiple linear and logistic regression models were used to examine the relationship between maternal urinary TCS and thyroid hormone levels. TCS was detectable (≥0.1 ng/mL) in 98.24% of maternal urine samples with tertile of urinary TCS levels: low (>0.1-2.75 μg/g.Cr), medium (2.75–9.78 μg/g.Cr), and high (9.78–427.38 μg/g.Cr). With adjustment for potential confounders, cord blood log(FT 3 )pmol/L concentration was 0.11 lower in newborns of mothers with medium and high urinary TCS levels compared with those with low levels. At third trimester, the high TCS concentration was associated with 0.03 [95% confidence interval (CI) −0.08, −0.02] lower maternal serum log(FT 4 )pmol/L, whereas the medium TCS concentration was associated with 0.15 (95% CI: −0.28, −0.03) lower serum log(TSH)mIU/L with adjustment for covariates. Our results suggest significant inverse associations between maternal urinary TCS and cord blood FT 3 as well as maternal blood FT 4 concentrations at third trimester. https://doi.org/10.1289/EHP500.

Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.).

PubMed

Özdemir, Selçuk; Altun, Serdar; Arslan, Harun

2018-01-01

Imidacloprid (IMI) is a neonicotinoid that is widely used for the protection of crops and carnivores from insects and parasites, respectively. It is well known that imidacloprid exposure has a harmful effect on several organisms. However, there is little information about imidacloprid toxicity in aquatic animals, particularly fish. Thus, in the current study, we assessed the histopathological changes; activation of iNOS, 8-OHdG and TNF-α; and expression levels of caspase 3, iNOS, CYP1A and MT1 genes in the common carp exposed to imidacloprid. For this purpose, fish were exposed to either a low dose (140 mg/L) or a high dose (280 mg/L) of imidacloprid for 24 h, 48 h, 72 h and 96 h. After IMI exposure, we detected hyperplasia of secondary lamellar cells and mucous cell hyperplasia in the gills, as well as hydropic degeneration in hepatocytes and necrosis in the liver. Moreover, 8-OHdG, iNOS and TNF-α activation was found particularly in the gills and liver but also moderately in the brain. Transcriptional analysis showed that caspase 3 expression was altered low dose and high doses of IMI for 72 h and 96 h exposure ( p <  0.05), iNOS expression was up-regulated with both low and high doses of IMI and in a time-dependent manner ( p <  0.05, p <  0.01, p <  0.001), CYP1A expression was not significantly changed regardless of the dose of IMI and exposure time ( p >  0.05) except with low and high doses of IMI for 96 h ( p <  0.05), and lastly, MT1 gene expression was up-regulated only in the brain with low doses of IMI for 96 h and high doses of IMI for 48 h, 72 h and 96 h exposure ( p <  0.05, p <  0.01). Our results indicated that acute IMI exposure moderately induce apoptosis in the brain but caused severe histopathological lesions, inflammation, and oxidative stress in the gills, liver, and brain of the common carp.

Methylated purines in urinary stones.

PubMed

Safranow, Krzysztof; Machoy, Zygmunt

2005-08-01

The aim of the study was to measure the content of methylated purines that appear as admixtures in uric acid stones. We analyzed urinary calculi from 48 residents of Western Pomerania who underwent surgery at the urology ward in Szczecin. Stone samples were dissolved in 0.1 mol/L NaOH. Extracts were diluted in 50 mmol/L KH(2)PO(4) and analyzed by reversed-phase HPLC with ultraviolet detection and use of a gradient of methanol concentration and pH. Uric acid was the main component of 9 stones. All 9 showed admixtures of 9 other purine derivatives: endogenous purine breakdown products (xanthine, hypoxanthine, and 2,8-dihydroxyadenine) and exogenous methyl derivatives of uric acid and xanthine (1-, 3-, and 7-methyluric acid; 1,3-dimethyluric acid; and 3- and 7-methylxanthine). Amounts of these purine derivatives ranged from the limit of detection to 12 mg/g of stone weight and showed a strong positive correlation (Spearman rank correlation coefficients, 0.63-0.94) with the uric acid content of the samples. The main methylated purine in the stones was 1-methyluric acid. Urinary purines at concentrations below their saturation limits may coprecipitate in samples supersaturated with uric acid and appear as admixtures in urinary stones. The amount of each purine depends on its average urinary excretion, similarity to the chemical structure of uric acid, and concentration of the latter in the stone. These findings suggest that purines in stones represent a substitutional solid solution with uric acid as solvent. Methylxanthines, which are ubiquitous components of the diet, drugs, and uric acid calculi, may be involved in the pathogenesis of urolithiasis.

Urinary paraben concentrations and in vitro fertilization outcomes among women from a fertility clinic.

PubMed

Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Messerlian, Carmen; Williams, Paige L; Sabatini, Mary E; Toth, Thomas L; Ford, Jennifer B; Calafat, Antonia M; Hauser, Russ

2016-03-01

To explore the relationship between urinary paraben concentrations and IVF outcomes among women attending an academic fertility center. Prospective cohort study. Fertility clinic in a hospital setting. A total of 245 women contributing 356 IVF cycles. None. Quantification of urinary concentrations of parabens by isotope-dilution tandem mass spectrometry, and assessment of clinical endpoints of IVF treatments abstracted from electronic medical records at the academic fertility center. Total and mature oocyte counts, proportion of high-quality embryos, fertilization rates, and rates of implantation, clinical pregnancy, and live births. The geometric means of the urinary concentrations of methylparaben, propylparaben, and butylparaben in our study population were 133, 24, and 1.5 μg/L, respectively. In models adjusted for age, body mass index, race/ethnicity, smoking status, and primary infertility diagnosis, urinary methylparaben, propylparaben, and butylparaben concentrations were not associated with IVF outcomes, specifically total and mature oocyte counts, proportion of high embryo quality, and fertilization rates. Moreover, no significant associations were found between urinary paraben concentrations and rates of implantation, clinical pregnancy, and live births. Urinary paraben concentrations were not associated with IVF outcomes among women undergoing infertility treatments. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Exposure to hexavalent chromium in welders: Results of the WELDOX II field study.

PubMed

Pesch, Beate; Lehnert, Martin; Weiss, Tobias; Kendzia, Benjamin; Menne, Eleonore; Lotz, Anne; Heinze, Evelyn; Behrens, Thomas; Gabriel, Stefan; Schneider, Wolfgang; Brüning, Thomas

2018-03-12

Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure. Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (rs) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration. Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75th percentile was 0.50 µg m-3, and 8 out of 50 (16%) welders exceeded 1 µg m-3. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m-3. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (rs 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (rs 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (rs 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (rs 0.78, 95% CI 0.69; 0.87). The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m-3. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.

Evidence for the Cost of Reproduction in Humans: High Lifetime Reproductive Effort Is Associated with Greater Oxidative Stress in Post-Menopausal Women

PubMed Central

Sancilio, Amelia; Galbarczyk, Andrzej; Klimek, Magdalena

2016-01-01

Life history theory predicts trade-offs between reproductive effort and maternal survivorship in energy-restricted environments. However, empirical evidence for the positive association between maternal mortality and reproductive effort from energetically challenged human populations are mixed and physiological mechanisms that may underlie this association are poorly understood. We hypothesized that increases in aerobic metabolism during repeated periods of pregnancy and lactation result in increased oxidative stress that may contribute to somatic deterioration, vulnerability to illness, and accelerated aging. We therefore predicted that lifetime gravidity and parity would be related to levels of biomarkers of oxidative stress, as well as antioxidative defence enzymes in post-menopausal women. Our hypothesis was supported by positive linear associations between levels of 8-OHdG, a biomarker of DNA oxidative damage (β = 0.21, p<0.05), levels of antioxidative defence enzyme Cu-Zn SOD (β = 0.25, p<0.05), and number of lifetime pregnancies. Furthermore, independent of age and health status, post-menopausal women with higher gravidity and parity (> = 4 pregnancies per lifetime) had 20% higher levels of 8-OHdG and 60% higher levels of Cu-Zn SOD compared to women with lower gravidity and parity (<4 pregnancies per lifetime). Our results present the first evidence for oxidative stress as a possible cost of reproductive effort in humans. PMID:26761206

Evidence for the Cost of Reproduction in Humans: High Lifetime Reproductive Effort Is Associated with Greater Oxidative Stress in Post-Menopausal Women.

PubMed

Ziomkiewicz, Anna; Sancilio, Amelia; Galbarczyk, Andrzej; Klimek, Magdalena; Jasienska, Grazyna; Bribiescas, Richard G

2016-01-01

Life history theory predicts trade-offs between reproductive effort and maternal survivorship in energy-restricted environments. However, empirical evidence for the positive association between maternal mortality and reproductive effort from energetically challenged human populations are mixed and physiological mechanisms that may underlie this association are poorly understood. We hypothesized that increases in aerobic metabolism during repeated periods of pregnancy and lactation result in increased oxidative stress that may contribute to somatic deterioration, vulnerability to illness, and accelerated aging. We therefore predicted that lifetime gravidity and parity would be related to levels of biomarkers of oxidative stress, as well as antioxidative defence enzymes in post-menopausal women. Our hypothesis was supported by positive linear associations between levels of 8-OHdG, a biomarker of DNA oxidative damage (β = 0.21, p<0.05), levels of antioxidative defence enzyme Cu-Zn SOD (β = 0.25, p<0.05), and number of lifetime pregnancies. Furthermore, independent of age and health status, post-menopausal women with higher gravidity and parity (> = 4 pregnancies per lifetime) had 20% higher levels of 8-OHdG and 60% higher levels of Cu-Zn SOD compared to women with lower gravidity and parity (<4 pregnancies per lifetime). Our results present the first evidence for oxidative stress as a possible cost of reproductive effort in humans.

Nandrolone administration with or without strenuous exercise promotes overexpression of nephrin and podocin genes and induces structural and functional alterations in the kidneys of rats.

PubMed

Tofighi, Asghar; Ahmadi, Shima; Seyyedi, Seyyedeh Masoumeh; Shirpoor, Alireza; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini

2018-01-05

Among the various adverse effects of nandrolone administration with or without strenuous exercise, kidney abnormalities, where there are associations between nandrolone decanoate consumption, have not been well defined yet. The aim of this study was to investigate the effect of nandrolone decanoate intake with or without strenuous exercise on nephrin and podocin gene expressions, cystatin C, oxidative DNA damage, and histological changes in the kidneys of rats. Thirty-two male wistar rats were assigned into four groups, namely control, nandrolone, nandrolone with strenuous exercise, and strenuous exercise groups. After six weeks of treatment, the results revealed a significant increase in the nephrin and podocin gene expression, plasma cystatin C, and the amount of 8-OHdG in the kidney tissue; as well as a decrease in creatinine clearance in nandrolone and nandrolone with strenuous exercise groups compared to the control group. Moreover, compared to the control group, the nandrolone and the nandrolone with strenuous exercise groups, showed histological changes such as fibrosis and kidney tissue cells proliferation. These findings indicate that nandrolone induces kidney abnormalities, which may in part be associated with overexpression of nephrin and podocin genes mediated by oxidative stress, which was manifested in increased 8-OHdG in kidney tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Short communication: Relationship between urinary neutrophil gelatinase-associated lipocalin and noninfectious pyuria in dogs.

PubMed

Proverbio, D; Spada, E; Baggiani, L; Bagnagatti De Giorgi, G; Ferro, E; Martino, P A; Perego, R

2015-01-01

Neutrophil gelatinase-associated lipocalin (NGAL) is a neutrophil-derived protein whose concentration increases in plasma and urine with ongoing renal damage. Urinary leucocytes can be a potential source of urinary NGAL. The aim of this study is to investigate the effects of urinary neutrophil count and other urinary parameters on urinary NGAL values in urine with negative culture. Urinalysis, urine culture, and determination of urinary NGAL were performed on 33 clinically healthy nonproteinuric dogs with negative urinoculture. The median uNGAL concentration in dogs in this study population was 9.74 ng/mL (IQR 1.93-25.43 ng/mL). In samples with WBCs > 5 hpf (mean 15.9, 6-50 leucocytes/hpf), median uNGAL value was significantly higher than that in samples with WBCs < 5 hpf (mean 0.9, 0-3 leucocytes/hpf), (4.96 pg/mL (0.29-11.34) and 23.65 pg/mL (20.04-29.80), resp.; P = 0.0053). The severity of urinary pyuria and the UPC value were correlated with uNGAL concentration. The results of our study show that urinary NGAL concentration is correlated with WBCs number in urinary sediment of dogs with negative urinoculture. The present study suggests that noninfectious pyuria is significantly correlated with urinary NGAL values and might influence uNGAL values.

Air exposure assessment and biological monitoring of manganese and other major welding fume components in welders.

PubMed

Ellingsen, Dag G; Dubeikovskaya, Larisa; Dahl, Kari; Chashchin, Maxim; Chashchin, Valery; Zibarev, Evgeny; Thomassen, Yngvar

2006-10-01

In a cross-sectional study, 96 welders were compared with 96 control subjects. Also 27 former welders, all diagnosed as having manganism, were examined. Exposure to welding fumes was determined in the 96 welders, while the concentration of elements in whole blood and urine was determined in all subjects. The geometric mean (GM) concentrations of manganese (Mn) and iron in the workroom air were 97 microg m(-3) (range 3-4620 microg m(-3); n=188) and 894 microg m(-3) (range 106-20 300 microg m(-3); n=188), respectively. Thus the Mn concentration in the workroom air was on average 10.6% (GM) of that of the Fe concentration. No substantial difference was observed in the air Mn concentrations when welding mild steel as compared to welding stainless steel. The arithmetic mean (AM) concentration of Mn in whole blood (B-Mn) was about 25% higher in the welders compared to the controls (8.6 vs. 6.9 microg l(-1); p < 0.001), while the difference in the urinary Mn concentrations did not attain statistical significance. A Pearson's correlation coefficient of 0.31 (p < 0.01) was calculated between B-Mn and Mn in the workroom air that was collected the day before blood sampling. Although the exposure to welding fumes in the patients had ceased on average 5.8 years prior to the study (range 4 years-7 years), their AM B-Mn concentration was still higher than in referents of similar age (8.7 microg l(-1) vs. 7.0 microg l(-1)). However, their urinary concentrations of cobolt, iron and Mn were all statistically significantly lower.

[Absence of effect of propranolol on urinary excretion of 3-methylhistidine in hyperthyroidism].

PubMed

Beylot, M; Riou, J P; Sautot, G; Mornex, R

Lean body mass and muscle protein breakdown were evaluated in euthyroid and hyperthyroid subjects by measuring the urinary excretion of creatinine and 3-methylhistidine. Since catecholamines probably have an inhibitory effect on muscle protein catabolism through a beta-receptor mechanism, the effects of propranolol on 3-methylhistidine excretion were also evaluated in hyperthyroid subjects. Hyperthyroid subjects had a lower lean body mass (34.9 +/- 6.3 kg versus 47.7 +/- 8.9 kg, p less than 0.001) and a greater 3-methylhistidine excretion (25.1 +/- 7.4 versus 19.0 +/- 4.8 mumol/mmol creatinine, p less than 0.05) than euthyroid subjects. Propranolol administered orally to hyperthyroid subjects decreased pulse rate (p less than 0.01) and plasma triiodothyronine concentrations (from 5.40 +/- 2.28 to 3.61 +/- 1.61 nmol/l, p less than 0.01), but did not modify urinary 3-methylhistidine excretion (24.8 +/- 8.7 versus 25.1 +/- 7.4 mumol/mmol creatinine). These results suggest that muscle wasting in hyperthyroidism is related to increased protein catabolism. This increased protein breakdown is not modified by short term administration of propranolol, a beta-blocking agent widely used in the management of hyperthyroidism.

Evaluation of novel urinary renal biomarkers with a cisplatin model of kidney injury: effects of collection period.

PubMed

Pinches, Mark D; Betts, Catherine J; Bickerton, Susan J; Beattie, Laura; Burdett, Lisa D; Thomas, Helen T; Derbyshire, Nicola A; Moores, Michele

2012-04-01

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. To date, all evaluation studies have been made using 18 to 24 hour collection periods. However, shorter, more welfare friendly, urine collection periods are also used in industry. In this article, we quantify urinary biomarker concentration in serial paired sequential short and long urine collections from male rats administered varying concentrations of cisplatin. We calculate the rate of biomarker excretion in normal animals for both collection periods and the bias and correlation in urinary biomarker concentration between collection periods in dosed and control animals, and we estimate the level of agreement in biomarker concentration between both collection periods. We conclude that although there are minor differences in the concentration of some urinary biomarkers that are dependent upon the time and duration of collection, shorter collection protocols do not influence subsequent interpretation of normalized urinary biomarker data for most biomarkers.

Ethion exposure and biological monitoring in vegetable farmers.

PubMed

Kongtip, Pornpimol; Changfuang, Sirinnapa; Yoosook, Witaya; Chantanakul, Suttinun; Sujirarat, Dusit

2011-03-01

To modify the method of analysis of urinary diethyl phosphate (DEP) in order to determine the relationship between atmospheric ethion concentration and urinary DEP concentration. A cross-sectional study was conducted by collecting atmospheric ethion in the breathing zone of 28 farmers following the NIOSH 5600 method. Urine samples were also collected to analyze urinary DEP concentrations by a modified method using a Gas Chromatography-Flame Photometric Detector (FPD). The average atmospheric ethion concentration in the breathing zone of farmers was 0.036 +/- 0.018 mg/m3. The average urinary DEP in pre-shift and post-shift was 0.030 +/- 0.06 and 0.851 +/- 1.80 mg/g of creatinine respectively. The average DEP during work shifts was 0.53 +/- 0.27, and ranged from 0.12 to 1.16 mg/g of creatinine. A high correlation coefficient (r = 0.645) was found between atmospheric ethion concentrations and urinary DEP concentrations at p < 0.001. The modified method provided a reliable result and the urinary DEP during work shifts was found to be a reliable biomarker of ethion exposure.

Sodium-bicarbonated mineral water decreases aldosterone levels without affecting urinary excretion of bone minerals.

PubMed

Schoppen, Stefanie; Pérez-Granados, Ana M; Carbajal, Angeles; Sarriá, Beatriz; Navas-Carretero, Santiago; Pilar Vaquero, M

2008-06-01

AIM To assess in healthy postmenopausal women the influence of consuming sodium-bicarbonated mineral water on postprandial evolution of serum aldosterone and urinary electrolyte excretion. Eighteen postmenopausal women consumed 500 ml of two sodium-bicarbonated mineral waters (sodium-bicarbonated mineral water 1 and sodium-bicarbonated mineral water 2) and a low-mineral water with a standard meal. Postprandial blood samples were taken at 60, 120, 240, 360 and 420 min and aldosterone concentrations were measured. Postprandial urinary minerals were determined. Urinary and total mineral excretion and urinary mineral concentrations did not differ except for sodium concentration, which was significantly higher with sodium-bicarbonated mineral water 1 than with low-mineral water (P = 0.005). There was a time effect (P = 0.003) on the aldosterone concentration. At 120 min, aldosterone concentrations were lower with sodium-bicarbonated mineral water 1 (P = 0.021) and sodium-bicarbonated mineral water 2 (P = 0.030) compared with low-mineral water. Drinking a sodium-rich bicarbonated mineral water with a meal increases urinary sodium concentration excretion without changes in the excretion of potassium and bone minerals.

Evaluation of genotoxicity in workers exposed to low levels of formaldehyde in a furniture manufacturing facility.

PubMed

Peteffi, Giovana Piva; da Silva, Luciano Basso; Antunes, Marina Venzon; Wilhelm, Camila; Valandro, Eduarda Trevizani; Glaeser, Jéssica; Kaefer, Djeine; Linden, Rafael

2016-10-01

Formaldehyde (FA) is a chemical widely used in the furniture industry and has been classified as a potential human carcinogen. The purpose of this study was to evaluate the occupational exposure of workers to FA at a furniture manufacturing facility and the relationship between environmental concentrations of FA, formic acid concentration in urine, and DNA damage. The sample consisted of 46 workers exposed to FA and a control group of 45 individuals with no history of occupational exposure. Environmental concentrations of FA were determined by high-performance liquid chromatography. Urinary formic acid concentrations were determined by gas chromatography with flame ionization detector. DNA damage was evaluated by the micronucleus (MN) test performed in exfoliated buccal cells and comet assay with venous blood. The 8-h time-weighted average of FA environmental concentration ranged from 0.03 ppm to 0.09 ppm at the plant, and the control group was exposed to a mean concentration of 0.012 ppm. Workers exposed to higher environmental FA concentrations had urinary formic acid concentrations significantly different from those of controls (31.85 mg L(-1) vs. 19.35 mg L(-), p ≤ 0.01 Mann-Whitney test). Significant differences were found between control and exposed groups for the following parameters: damage frequency and damage index in the comet assay, frequency of binucleated cells in the MN test, and formic acid concentration in urine. The frequency of micronuclei, nuclear buds, and karyorrhexis did not differ between groups. There was a positive correlation between environmental concentrations of FA and damage frequency (Spearman's rank correlation coefficient [r s] = 0.24), damage index (r s = 0.21), binucleated cells (r s = 0.34), and urinary formic acid concentration (r s = 0.63). The results indicate that, although workers in the furniture manufacturing facility were exposed to low environmental levels of FA, this agent contributes to the observed increase in cytogenetic damage. In addition, urinary formic acid concentrations correlated strongly with occupational exposure to FA. © The Author(s) 2015.

Exposure to organophosphate flame retardants in spray polyurethane foam applicators: Role of dermal exposure.

PubMed

Bello, Anila; Carignan, Courtney C; Xue, Yalong; Stapleton, Heather M; Bello, Dhimiter

2018-04-01

Spray polyurethane foam (SPF) is a highly effective thermal insulation material that has seen considerable market growth in the past decade. Organophosphate flame retardants (PFRs) are added to SPF formulations to meet fire code requirements. A common flame retardant used in SPF formulations is tris 1-chloro 2-propyl phosphate (TCIPP), a suspected endocrine disruptor. Exposure monitoring efforts during SPF applications have focused primarily on the isocyanate component, a potent respiratory and dermal sensitizer. However, to our knowledge, there is no monitoring data for TCIPP. To characterize occupational exposures to TCIPP and other flame retardants during SPF insulation. Workers at four SPF insulation sites and one foam removal site (total n = 14) were recruited as part of this pilot study. Personal inhalation exposure to TCIPP was monitored with a CIP-10MI inhalable sampler and potential dermal exposure was assessed through the use of a glove dosimeter. Biomarkers of TCIPP and three other PFRs were measured in urine collected from workers pre-and post-shift. Linear mixed effect models were used to analyze associations of urinary biomarkers with inhalation and dermal exposures and paired t-tests were used to examine the difference on the means of urinary biomarkers pre-and post-shift. Chemical analysis of all species was performed with liquid chromatography-electrospray ionization tandem mass spectrometry. Geometric mean (GM) concentrations of TCIPP in personal air monitors and glove dosimeters collected from SPF applicators, 294.7 μg/m 3 and 18.8 mg/pair respectively. Overall, GM concentrations of the two TCIPP urinary biomarkers BCIPP and BCIPHIPP and (6.2 and 88.8 μg/mL) were 26-35 times higher than reported in the general population. Post-shift levels of TCIPP biomarkers were higher than pre-shift even though workers at insulation sites wore supplied air respirators, gloves and coveralls. The urinary biomarkers for the other PFRs were not elevated post shift. Concentrations of TCIPP on glove dosimeters were positively associated with post-shift urinary TCIPP biomarkers (p < 0.05) whereas concentrations in personal air samples were not. High levels of urinary biomarkers for TCIPP among SPF applicators, including post-shift, points to absorption of TCIPP during the work shift, in spite of the use of best industry exposure control practices. Dermal exposure appears to be an important, if not the primary exposure pathway for TCIPP, although inhalation or incidental ingestion of foam particles post-SPF application cannot be ruled out in this pilot study. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nutrition and lower urinary tract disease in cats.

PubMed

Bartges, Joseph W; Kirk, Claudia A

2006-11-01

Lower urinary tract disease occurs commonly in cats and is often associated with crystal-related disease. Dietary modification is beneficial in managing some of these diseases, including idiopathic cystitis, urolithiasis, and urethral matrix-crystalline plugs. Altering dietary formulation may result in decreasing urinary concentrations of crystallogenic compounds, increasing urinary concentrations fo crystallogenic inhibitors, and diluting urine composition.

Amino Acid Metabolism in Acute Renal Failure: Influence of Intravenous Essential L-Amino Acid Hyperalimentation Therapy

PubMed Central

Abel, Ronald M.; Shih, Vivian E.; Abbott, William M.; Beck, Clyde H.; Fischer, Josef E.

1974-01-01

A solution of 8 essential I-amino acids and hypertonic dextrose was administered to 5 patients in acute postoperative renal failure in a program of hyperalimentation designed to decrease the patient's catabolic state and to accrue certain metabolic benefits. A sixth patient receiving intravenous glucose alone served as a control. The pretreatment plasma concentrations of amino acids in all 6 patients did not differ significantly from normal; following intravenous essential amino acids at a dose of approximately 12.6 gm/24 hours, no significant elevations out of the normal range of these substances occurred. Since urinary excretion rates did not dramatically increase, urinary loss was excluded as a possible cause for the failure of increase of plasma concentrations. The results suggest that the administration of an intravenous solution of 1-amino acids and hypertonic dextrose is associated with rapid clearance from the blood of these substances and, with a failure of increased urinary excretion, indirect evidence of amino acid utilization for protein synthesis has been obtained. Histidine supplementation in patients with acute renal failure is probably unnecessary based on the lack of significant decreases in histidine concentrations in these patients. PMID:4850497

Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

PubMed

Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

2009-08-01

The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

Urinary 8-hydroxy-2'-deoxyguanosine (8-oxodG) level can predict acute renal damage in young children with urinary tract infection.

PubMed

Chien, Jien-Wen; Wang, Lien-Yen; Cheng, Yu-Shan; Tsai, Yi-Giien; Liu, Chin-San

2014-06-01

There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI). Children (N = 73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement. Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than patients with normal DMSA findings. High level of urinary 8-oxodG may be a risk factor of severe renal damage.

Characterization of Proteinuria in Dogue de Bordeaux Dogs, a Breed Predisposed to a Familial Glomerulonephropathy: A Retrospective Study.

PubMed

Lavoué, Rachel; Trumel, Catherine; Smets, Pascale M Y; Braun, Jean-Pierre; Aresu, Luca; Daminet, Sylvie; Concordet, Didier; Palanché, Florence; Peeters, Dominique

2015-01-01

Dogue de Bordeaux dog has been reported to be predisposed to a familial glomerulonephropathy that displays some morphological modifications reported in focal and segmental glomerulosclerosis. Prevalence of quantitatively abnormal renal proteinuria was recently reported to be 33% in this breed. The nature of the proteinuria was assessed by sodium dodecyl sulfate-agarose gel electrophoresis and determinations of urinary markers (urinary retinol-binding protein, urinary N-acetyl-β-glucosaminidase, urinary albumin and urinary immunoglobulin G) on stored specimens. Diagnostic performances of sodium dodecyl sulfate-agarose gel electrophoresis to identify dogs with elevated urinary biomarkers were assessed. Samples from 102 adult Dogue de Bordeaux dogs (47 non-proteinuric [urine protein-to-creatinine ratio ≤ 0.2], 20 borderline-proteinuric [0.2< urine protein-to-creatinine ratio ≤ 0.5] and 35 proteinuric dogs [urine protein-to-creatinine ratio >0.5]) were used, of which 2 were suffering from familial glomerulonephropathy. The electrophoretic protein patterns, for all but one proteinuric dog, were indicative of a glomerular origin and, in all dogs, the urinary albumin concentration related to creatinine concentration and the urinary immunoglobulin G concentration related to creatinine concentration were above the upper limit of the reference interval established for the breed. Sensitivity and specificity of sodium dodecyl sulfate-agarose gel electrophoresis identifying dogs with elevated urinary albumin concentration were 94% and 92%, respectively, while diagnostic performance of sodium dodecyl sulfate-agarose gel electrophoresis in detecting dogs with elevated urinary immunoglobulin G concentration yielded sensitivity and specificity of 90% and 74%, respectively. These results suggest that all proteinuric and some borderline-proteinuric Dogue de Bordeaux dogs likely have underlying glomerular lesions and that sodium dodecyl sulfate-agarose gel electrophoresis and urinary markers might be useful to screen dogs with borderline-proteinuria. Additional investigations are warranted to assess if these findings are related to the familial glomerulonephropathy.

Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications.

PubMed

Liu, Xinle; Gan, Wei; Zou, Yuangao; Yang, Bin; Su, Zhenzhen; Deng, Jin; Wang, Lanlan; Cai, Jianping

2016-01-01

The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age- and sex-matched healthy controls. Urinary levels of DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8-oxodGuo and 8-oxoGuo in diabetes patients with/without complications compared with age-matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8-oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8-oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications.

Association of oxidative DNA damage, protein oxidation and antioxidant function with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers during fetal circulation.

PubMed

Negi, Reena; Pande, Deepti; Karki, Kanchan; Kumar, Ashok; Khanna, Ranjana S; Khanna, Hari D

2014-02-05

Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

L-Selenomethionine Does not Protect Against Testosterone Plus 17β-Estradiol-Induced Oxidative Stress and Pre-Neoplastic Lesions in the Prostate of NBL Rats

PubMed Central

Özten, Nur; Schlicht, Michael; Diamond, Alan M.; Bosland, Maarten C.

2014-01-01

Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including one study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T+E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3.0 mg selenium/kg in NIH-07 diet in Nbl/Crl rats treated with T+E2 for 16 weeks. Hormone treatment increased immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) in the prostatic sites of T+E2-induced preneoplasia (p<0.05), but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity and mRNA expression were induced by T+E2 (p<0.05–p<0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathione-peroxidase and MnSOD, except for a reduction of MnSOD protein expression in the lateral prostate (p<0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (p<0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T+E2 occurred in the lateral and dorsal prostate, explaining why T+E2 induces lesions selectively in the lateral lobe of NBL rats. PMID:24773027

L-selenomethionine does not protect against testosterone plus 17β-estradiol-induced oxidative stress and preneoplastic lesions in the prostate of NBL rats.

PubMed

Özten, Nur; Schlicht, Michael; Diamond, Alan M; Bosland, Maarten C

2014-01-01

Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including 1 study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T + E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3.0 mg selenium/kg in NIH-07 diet in Noble (Nbl)/Crl rats treated with T + E2 for 16 wk. Hormone treatment increased immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) in the prostatic sites of T + E2-induced preneoplasia (P < 0.05), but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity (P < 0.05) and mRNA expression were induced by T + E2 (P < 0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathione-peroxidase and MnSOD, except for a reduction of MnSOD protein expression in the lateral prostate (P < 0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (P < 0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T + E2 occurred in the lateral and dorsal prostate, explaining why T + E2 induces lesions selectively in the lateral lobe of NBL rats.

Chemopreventive effect of selenium and Chinese medicinal herbs on N-nitrosobis(2-oxopropyl)amine-induced hepatocellular carcinoma in Syrian hamsters.

PubMed

Lee, Chang-Yin; Hsu, Yi-Chao; Wang, Jir-You; Chen, Chien-Chih; Chiu, Jen-Hwey

2008-07-01

Oxidative DNA damage by reactive oxygen species is involved in the process of liver carcinogenesis. To test the hypothesis that a remedy containing Scutellaria baicalensis Georgi (Sb) and Bupleurum scorzonerifolfium Willd (Bs) (Sb/Bs remedy) modulates hepatic neoplastic growth, BOP (N-nitrosobis(2-oxopropyl)amine)-induced liver cancers in hamsters were established. Parameters such as survival rate, tumour area, tumour foci, 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, transforming growth factor (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) were measured after Sb/Bs remedy treatment during BOP-induced carcinogenesis. The results showed that the Sb/Bs remedy and its constituents Sb and Bs suppressed the tumour area in BOP-induced liver tumours. Because selenium (Sel) is toxic at a high dose (10 mg/kg), with a low survival rate (0%), the combination of Sb/Bs remedy and low-dose Sel (1 mg/kg) was found to decrease the tumour area and the number of tumour foci while increasing serum TNF-alpha and TGF-beta1, but not IL-6 levels. Besides, the Sb/Bs remedy, when combined with low-dose Sel, not only decreased the expression of 8-OHdG and increased caspase-3 expression within the glutathione S-transferase placental form-positive tumour foci but also increased tumour apoptosis in BOP-induced hamsters. We conclude that low-dose Sel has a chemoprevention effect on BOP-induced liver tumours and such an effect was more enhanced when combined with Sb/Bs treatment.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

PubMed

Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

2015-09-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Obstructive sleep apnoea and related comorbidities in incident idiopathic pulmonary fibrosis.

PubMed

Gille, Thomas; Didier, Morgane; Boubaya, Marouane; Moya, Loris; Sutton, Angela; Carton, Zohra; Baran-Marszak, Fanny; Sadoun-Danino, Danielle; Israël-Biet, Dominique; Cottin, Vincent; Gagnadoux, Frederic; Crestani, Bruno; d'Ortho, Marie-Pia; Brillet, Pierre-Yves; Valeyre, Dominique; Nunes, Hilario; Planès, Carole

2017-06-01

The objectives of this prospective study were: 1) to determine the prevalence and determinants of obstructive sleep apnoea (OSA) in patients with newly diagnosed idiopathic pulmonary fibrosis (IPF); 2) to determine whether OSA was associated with cardiovascular disease (CVD) as well as increased oxidative stress and levels of IPF biomarkers in the blood.A group of 45 patients with newly diagnosed IPF attended polysomnography. The prevalence of CVD and the severity of coronary artery calcification were investigated by high-resolution computed tomography. The levels of 8-hydroxydeoxyguanosine (8-OH-DG) and various IPF biomarkers in the blood were compared between patients with no or mild OSA (apnoea-hypopnoea index (AHI) <15 events·h -1 ), with moderate OSA (15 ≤AHI <30 events·h -1 ) and with severe OSA (AHI ≥30 events·h -1 ).The prevalence of moderate-to-severe OSA and severe OSA was 62% and 40%, respectively. AHI did not correlate with demographic or physiological data. All patients with severe OSA had a medical history of CVD, versus 41.2% and 40% of those with no or mild OSA, or with moderate OSA, respectively (p<0.0001). Ischaemic heart disease (IHD) and moderate-to-severe coronary artery calcifications were strongly associated with severe OSA. The 8-OH-DG and matrix metalloproteinase-7 serum levels were significantly increased in the severe OSA group.Moderate-to-severe OSA is highly prevalent in incident IPF and severe OSA is strongly associated with the presence of CVD, particularly IHD. Copyright ©ERS 2017.

Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Hui; Shi, Qiong; Song, Xiufang

2015-07-01

Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observedmore » phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.« less

Cardiometabolic risk factors are associated with high urinary enterolactone concentration, independent of urinary enterodiol concentration and dietary fiber intake in adults.

PubMed

Frankenfeld, Cara L

2014-09-01

The study objective was to evaluate independent and interactive associations of dietary fiber intake and high urinary enterolignans with cardiometabolic risk factors. The analysis included 2260 adults (≥20 y of age) from the 2003-2010 NHANES. Logistic regression models were used to evaluate obesity and clinically defined cardiometabolic risk factors in relation to dietary fiber intake and urinary enterolignan concentrations. Three sets of models were created: 1) independent associations, 2) mutually adjusted associations, and 3) interactions. Models were adjusted for age, gender, race/ethnicity, education, smoking status, and energy intake. High concentrations were considered to be above the 90th percentile of urinary enterolignan concentrations. Increasing dietary fiber intake was associated with high blood pressure (P = 0.02) and low serum HDL cholesterol (P-trend = 0.03). High urinary enterodiol concentration was not associated with obesity or cardiometabolic risk factors. High urinary enterolactone concentration was inversely associated with obesity (OR: 0.44; 95% CI: 0.29, 0.66), abdominal obesity (OR: 0.58; 95% CI: 0.39, 0.87), high serum C-reactive protein (CRP; OR: 0.52; 95% CI: 0.37, 0.74), high serum triglycerides (OR: 0.39; 95% CI: 0.23, 0.61), low serum HDL cholesterol (OR: 0.37; 95% CI: 0.23, 0.61), and metabolic syndrome (OR: 0.47; 95% CI: 0.30, 0.74). In mutually adjusted models, enterolactone associations observed in independent models remained similar, but associations for dietary fiber intake were attenuated, with the exception of blood pressure. In interaction models, there were 2 significant interactions: between high urinary enterodiol concentration and dietary fiber intake for high serum CRP (P = 0.04) and high plasma glucose (P = 0.04). Overall, being in the highest 10% of urinary enterolactone concentration was associated with cardiometabolic risk factors, independent of dietary fiber intake and enterodiol concentration. Future studies are warranted to evaluate physiologic actions of enterolactone or aspects of the gut microbial profile responsible for lignan metabolism to enterolactone. © 2014 American Society for Nutrition.

An epidemiological survey of children's iodine nutrition and goitre status in regions with mildly excessive iodine in drinking water in Hebei Province, China.

PubMed

Lv, Shengmin; Zhao, Jun; Xu, Dong; Chong, Zhenshui; Chong, Zhengshui; Jia, Lihui; Du, Yonggui; Ma, Jing; Rutherford, Shannon

2012-07-01

To identify children's iodine nutrition and goitre status in areas with mildly excessive iodine in drinking water. A cross-sectional survey. Probability proportional to size sampling was employed to randomly select children from thirty townships where the median iodine content in drinking water ranged from 150 to 300 μg/l; their urinary iodine concentrations were determined and their thyroid volumes were measured by ultrasound. Drinking water samples and salt samples from the villages where the children lived were collected using a systematic sampling method. Hebei Province of China. A total of 1259 children aged 8-10 years (621 boys and 638 girls). Children's median urinary iodine concentration was found to be 418·8 μg/l, and the iodine concentration was >300 μg/l for 68·3 % (248/363) of the urine samples. Children's median urinary iodine concentration in villages with median salt iodine >10 mg/kg was significantly higher than that in villages with median salt iodine <5 mg/kg (442·9 μg/l v. 305·4 μg/l, P ≈ 0). The goitre rate of 1259 children examined by ultrasound was 10·96 %. The iodine intake of children living in areas with mildly excessive iodine in drinking water in Hebei Province was found to be excessive. The measured iodine excess in the sampled children is exacerbated by consumption of iodized salt. Goitre was identified in these areas; however, due to the limitation of the current criteria for children's thyroid volume, a comprehensive assessment of the prevalence of goitre in these regions could not be made and further study is required.

Cadmium body burden and increased blood pressure in middle-aged American Indians: the Strong Heart Study.

PubMed

Franceschini, N; Fry, R C; Balakrishnan, P; Navas-Acien, A; Oliver-Williams, C; Howard, A G; Cole, S A; Haack, K; Lange, E M; Howard, B V; Best, L G; Francesconi, K A; Goessler, W; Umans, J G; Tellez-Plaza, M

2017-03-01

Cadmium (Cd) is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of Cd with hypertension has been inconsistent. We studied the association between urinary Cd concentrations, a measure of total body burden, and blood pressure in American Indians, a US population with above national average Cd burden. Urinary Cd was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking antihypertensive medications), urinary Cd ranged from 0.01 to 78.48 μg g -1 creatinine (geometric mean=0.94 μg g -1 ) and it was correlated with smoking pack-year among ever-smokers (r 2 =0.16, P<0.0001). Participants who were smokers were on average light-smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88 μg g -1 creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration (β)=1.64, P=0.002). These associations were present among light- and never-smokers (β=2.03, P=0.002, n=2627), although not significant among never-smokers (β=1.22, P=0.18, n=1260). Cd was also associated with diastolic blood pressure among light- and never-smokers (β=0.94, P=0.004). These findings suggest that there is a relationship between Cd body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk.

Cadmium body burden and increased blood pressure in middle-aged American Indians: the Strong Heart Study

PubMed Central

Franceschini, Nora; Fry, Rebecca; Balakrishnan, Poojitha; Navas-Acien, Ana; Oliver-Williams, Clare; Howard, Annie G; Cole, Shelley A; Haack, Karin; Lange, Ethan M.; Howard, Barbara V.; Best, Lyle G; Francesconi, Kevin A.; Goessler, Walter; Umans, Jason G; Tellez-Plaza, Maria

2016-01-01

Cadmium is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of cadmium with hypertension has been inconsistent. We studied the association between urinary cadmium concentrations, a measure of total body burden, and blood pressure in American Indians, a U.S. population with above national average cadmium burden. Urinary cadmium (Cd) was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3,714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking anti-hypertensive medications), urinary Cd ranged from 0.01 to 78.48 μg/g creatinine (geometric mean=0.94 μg/g) and it was correlated with smoking pack-year among ever-smokers (r2=0.16, P<0.0001). Participants who were smokers were on average light smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88 μg/g creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs. never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration [β]=1.64, P=0.002). These associations were present among light- and never-smokers (β=2.03, P=0.002, n=2,627), although not significant among never-smokers (β=1.22, P=0.18, n=1,260). Cd was also associated with diastolic blood pressure among light- and never-smokers (β=0.94, P=0.004). These findings suggest there is a relationship between cadmium body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk. PMID:27629244

Dietary predictors of urinary environmental biomarkers in young girls, BCERP, 2004-7.

PubMed

Mervish, Nancy; McGovern, Kathleen J; Teitelbaum, Susan L; Pinney, Susan M; Windham, Gayle C; Biro, Frank M; Kushi, Lawrence H; Silva, Manori J; Ye, Xiaoyun; Calafat, Antonia M; Wolff, Mary S

2014-08-01

Exposures of children to phthalates, parabens, and bisphenol-A (BPA) are of concern because of their hormonal potential. These agents are found in a wide range of foods and packaging. We investigated whether intake of certain foods predict exposures to these chemicals in young girls. Among 1101 girls (6-8 years at enrollment) from the Breast Cancer and Environment Research Program (BCERP) study, we measured urinary exposure biomarkers for phthalates, parabens, and BPA and assessed dietary intake using 24-h recall 2-4 times. We examined the average daily servings of major and minor food groups categorized as 0 to <0.5, 0.5 to <1 and ≥ 1 servings per day. Items included dairy, eggs, fats, fish, fruit, single grains, meat, non-poultry meats, pasta, poultry and vegetables. Covariate-adjusted least squares geometric means and 95% confidence intervals of creatinine-corrected phthalate and phenol metabolite concentrations in urine were calculated in relation to food intake. Grains, flour and dry mixes and total fish consumption were positively associated with BPA and the sum of four di-2-ethylhexylphthalate (DEHP) urinary metabolite concentrations. Non-fresh vegetables and poultry were both positively associated with BPA and paraben urinary concentrations. Fats, oils and poultry consumption were positively associated with BPA. Whole-fat dairy consumption was associated with ΣDEHP. Some foods may contribute to child exposures to certain chemicals, and this may constitute modifiable means to reduce these environmental exposures. Copyright © 2014 Elsevier Inc. All rights reserved.

Application of Liquid Chromatography-Tandem Mass Spectrometry To Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes?

PubMed

Logue, Caomhan; Dowey, Le Roy C; Strain, J J; Verhagen, Hans; McClean, Stephen; Gallagher, Alison M

2017-06-07

Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10-1000 ng/mL with coefficients of determination ranging from 0.9969 to 0.9997. Accuracy ranged from 92 to 104%, and intrabatch and interday precisions were within acceptable limits with %CV below 8% for all compounds. A double-blind, randomized crossover dose-response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes of sampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p < 0.001), whereas for sucralose, urinary concentrations were useful for distinguishing between low (0.1% ADI) and high doses (10% ADI) only (p < 0.001). In summary, this biomarker approach may be useful for assessing intakes of five commonly consumed LCSs.

[Assessment of dietary habits related to iodine intake and iodine concentration and thyroid dysfunction in a non-preselected population in Spain (the Thyrobus Project)].

PubMed

Ballester, Lluís Vila; Candil, Sergio Donnay; Reymunde, Teresa Iglesias; Escofet, Federico Soriguer; Henzi, Frederic Tortosa; Jaramillo, Sara Torrejón; Alcázar, Javier; Tapias, María José; Torres, Yolanda; Puig-Domingo, Manel

2010-11-01

Most of the studies on urinary iodine levels in Spain in the last decade have reported a significant improvement. A survey was undertaken together with an information campaign on the thyroid gland, the importance of iodine intake and hypothyroidism in four Spanish cities. The goals of the survey were to obtain information on consumption of iodine-containing foods, to measure urinary iodine levels and to evaluate the prevalence of thyroid dysfunction. A non-preselected population attending the information campaign centers located in Barcelona, La Coruña, Malaga and Madrid was studied. A questionnaire on fish, milk and iodized salt consumption was administered. Urinary iodine levels (Pino's method) and thyrotropin (TSH) concentrations (Whatman 903® dry paper method) were measured. A total of 872 questionnaires were completed (Madrid 40%; La Coruña 27%; Malaga 19%; and Barcelona 14%). The mean age was 51 years (SD 16); 81% were women. A total of 60.6% of interviewees reported they consumed iodized salt, 90.8% reported daily milk intake and 29.3% reported fish consumption ≥3 times per week. The mean urinary iodine concentration was 143.2 μg/L. The prevalence of high TSH levels (>4 mUI/L) was 1.3% and that of low TSH levels (<0.4 mUI/mL) was 1.2%. According to the World Health Organization criteria, the median urinary iodine concentration, both overall or by city, is indicative of optimal iodine intake. In addition to iodized salt intake, consumption of products such as milk and fish has probably contributed to these positive results. The prevalences of undiagnosed hyperthyroidism and hypothyroidism detected in this study were similar to those found in other studies. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

Characterization of Urinary Phthalate Metabolites Among Custodians

PubMed Central

Cavallari, Jennifer M.; Simcox, Nancy J.; Wakai, Sara; Lu, Chensheng; Garza, Jennifer L.; Cherniack, Martin

2015-01-01

Phthalates, a ubiquitous class of chemicals found in consumer, personal care, and cleaning products, have been linked to adverse health effects. Our goal was to characterize urinary phthalate metabolite concentrations and to identify work and nonwork sources among custodians using traditional cleaning chemicals and ‘green’ or environmentally preferable products (EPP). Sixty-eight custodians provided four urine samples on a workday (first void, before shift, end of shift, and before bedtime) and trained observers recorded cleaning tasks and types of products used (traditional, EPP, or disinfectant) hourly over the work shifts. Questionnaires were used to assess personal care product use. Four different phthalate metabolites [monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethylhexyl) phthalate (MEHP), and monobenzyl phthalate (MBzP)] were quantified using liquid chromatography mass spectrometry. Geometric means (GM) and 95% confidence intervals (95% CI) were calculated for creatinine-adjusted urinary phthalate concentrations. Mixed effects univariate and multivariate modeling, using a random intercept for each individual, was performed to identify predictors of phthalate metabolites including demographics, workplace factors, and personal care product use. Creatinine-adjusted urinary concentrations [GM (95% CI)] of MEP, MMP, MEHP, and MBzP were 107 (91.0–126), 2.69 (2.18–3.30), 6.93 (6.00–7.99), 8.79 (7.84–9.86) µg g−1, respectively. An increasing trend in phthalate concentrations from before to after shift was not observed. Creatinine-adjusted urinary MEP was significantly associated with frequency of traditional cleaning chemical intensity in the multivariate model after adjusting for potential confounding by demographics, workplace factors, and personal care product use. While numerous demographics, workplace factors, and personal care products were statistically significant univariate predictors of MMP, MEHP, and MBzP, few associations persisted in multivariate models. In summary, among this population of custodians, we identified both occupational and nonoccupational predictors of phthalate exposures. Identification of phthalates as ingredients in cleaning chemicals and consumer products would allow workers and consumers to avoid phthalate exposure. PMID:26240196

Relation of dietary inorganic arsenic exposure and urinary inorganic arsenic metabolites excretion in Japanese subjects.

PubMed

Oguri, Tomoko; Yoshinaga, Jun; Suzuki, Yayoi; Tao, Hiroaki; Nakazato, Tetsuya

2017-06-03

Inorganic arsenic (InAs) is a ubiquitous metalloid that has been shown to exert multiple adverse health outcomes. Urinary InAs and its metabolite concentration has been used as a biomarker of arsenic (As) exposure in some epidemiological studies, however, quantitative relationship between daily InAs exposure and urinary InAs metabolites concentration has not been well characterized. We collected a set of 24-h duplicated diet and spot urine sample of the next morning of diet sampling from 20 male and 19 female subjects in Japan from August 2011 to October 2012. Concentrations of As species in duplicated diet and urine samples were determined by using liquid chromatography-ICP mass spectrometry with a hydride generation system. Sum of the concentrations of urinary InAs and methylarsonic acid (MMA) was used as a measure of InAs exposure. Daily dietary InAs exposure was estimated to be 0.087 µg kg -1 day -1 (Geometric mean, GM), and GM of urinary InAs+MMA concentrations was 3.5 ng mL -1 . Analysis of covariance did not find gender-difference in regression coefficients as significant (P > 0.05). Regression equation Log 10 [urinary InAs+MMA concentration] = 0.570× Log 10 [dietary InAs exposure level per body weight] + 1.15 was obtained for whole data set. This equation would be valuable in converting urinary InAs concentration to daily InAs exposure, which will be important information in risk assessment.

Fecal and urinary N-methylhistamine concentrations in dogs with chronic gastrointestinal disease.

PubMed

Berghoff, Nora; Hill, Steve; Parnell, Nolie K; Mansell, Joanne; Suchodolski, Jan S; Steiner, Jörg M

2014-09-01

Due to their ability to release inflammatory mediators, such as histamine, mast cells are potentially important in gastrointestinal disease. The purpose of this study was to measure N-methylhistamine (NMH), a histamine metabolite, in fecal and urine samples from dogs with chronic gastrointestinal disease. Fecal and urinary NMH concentrations were compared between dogs with chronic gastrointestinal disease and control dogs, and/or to control ranges. Correlation between fecal and urinary NMH concentrations, serum C-reactive protein (CRP) concentration, the clinical disease activity index (CCECAI), and gastrointestinal mucosal mast cell numbers (where available) in dogs with gastrointestinal disease was evaluated. Seven of 16 dogs with gastrointestinal disease had increased urinary or fecal NMH concentrations, but there was no correlation between NMH concentrations and the CCECAI or mucosal mast cells numbers. Urinary NMH concentrations were positively associated with histological grading and serum CRP concentrations. The lack of correlation between NMH concentrations and the CCECAI suggests that NMH may not be a good marker for clinical disease activity in dogs as determined by the CCECAI. Based on their association with severity of intestinal mucosal inflammation, urinary NMH concentrations may potentially have clinical utility as a marker of intestinal inflammation in certain groups of dogs with chronic gastrointestinal disease, but future studies in a larger number of dogs are necessary to further characterize the role of mast cell-mediated inflammation in dogs with chronic gastrointestinal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Urinary levoglucosan as a biomarker for woodsmoke exposure in wildland firefighters.

PubMed

Naeher, Luke P; Barr, Dana Boyd; Adetona, Olorunfemi; Simpson, Christopher D

2013-01-01

Levoglucosan, a sugar anhydride and a combustion breakdown product of cellulose is a dominant organic constituent of particles in woodsmoke. After exposure, levoglucosan is excreted unmetabolized in urine. Urinary levoglucosan was assessed as a biomarker of occupational woodsmoke exposure among wildland firefighters. Urine samples were collected from wildland firefighters before and after their work-shifts on days when they worked at prescribed burns. A total of 97 pairs of pre- and post-shift urine samples were collected from 19 firefighters over 10 prescribed burn shifts. The urine samples were analyzed to determine whether there was an increase in the concentration of levoglucosan from pre- to post-shift after the firefighters had worked at the prescribed burns. Overall, there was an increase in both the urinary volume-based and creatinine corrected levoglucosan concentrations from pre- to post-shift (P < 0.05). However, the direction of change in the concentrations was not consistent. There were increases in urinary levoglucosan concentration from pre- to post-shift in 63% of the person-day samples, and in only 58% of the person-day samples for the creatinine corrected concentrations. Although there was an overall increase in urinary concentrations of levoglucosan, results suggest that other sources apart from woodsmoke affected the urinary levels of this biomarker in wildland firefighters. Therefore, urinary levoglucosan may not be effective as a biomarker of woodsmoke exposure in this setting.

Relevance of dietary protein concentration and quality as risk factors for the formation of calcium oxalate stones in cats.

PubMed

Paßlack, Nadine; Burmeier, Hannes; Brenten, Thomas; Neumann, Konrad; Zentek, Jürgen

2014-01-01

The role of dietary protein for the development of feline calcium oxalate (CaOx) uroliths has not been conclusively clarified. The present study evaluated the effects of a varying dietary protein concentration and quality on critical indices for the formation of CaOx uroliths. Three diets with a high protein quality (10-11 % greaves meal/diet) and a varying crude protein (CP) concentration (35, 44 and 57 % in DM) were compared. Additionally, the 57 % CP diet was compared with a fourth diet that had a similar CP concentration (55 % in DM), but a lower protein quality (34 % greaves meal/diet). The Ca and oxalate (Ox) concentrations were similar in all diets. A group of eight cats received the same diet at the same time. Each feeding period was divided into a 21 d adaptation period and a 7 d sampling period to collect urine. There were increases in urinary volume, urinary Ca concentrations, renal Ca and Ox excretion and urinary relative supersaturation (RSS) with CaOx with increasing dietary protein concentrations. Urinary pH ranged between 6·34 and 6·66 among all groups, with no unidirectional effect of dietary protein. Lower renal Ca excretion was observed when feeding the diet with the lower protein quality, however, the underlying mechanism needs further evaluation. In conclusion, although the observed higher urinary volume is beneficial, the increase in urinary Ca concentrations, renal Ca and Ox excretion and urinary RSS CaOx associated with a high-protein diet may be critical for the development of CaOx uroliths in cats.

Urinary 3-hydroxypropyl mercapturic acid (3-HPMA) concentrations in dogs with acute spinal cord injury due to intervertebral disc herniation.

PubMed

Sangster, A M; Zheng, L; Bentley, R T; Shi, R; Packer, R A

2017-01-01

The aim of this study was to investigate urinary 3-hydroxypropyl mercapturic acid (3-HPMA), a metabolite of acrolein, as a novel biomarker in acute spinal cord injury (ASCI) due to intervertebral disc herniation in dogs. Urine from 10 client-owned dogs with ASCI collected at presentation and 10 control dogs was analyzed for 3-HPMA. The median urinary 3-HPMA concentration in ASCI dogs was significantly higher than in control dogs, but was not correlated with the severity of ASCI. The median urinary 3-HPMA concentration in intact dogs was higher than in neutered dogs. Higher urinary 3-HPMA concentrations in dogs after ASCI support a role for acrolein, a cytotoxic by-product of lipid peroxidation, in canine ASCI. Urinary 3-HPMA could be used as a biomarker in future clinical trials to measure the effect of therapeutic intervention of reducing acrolein after ASCI. Copyright © 2016. Published by Elsevier Ltd.

Occupational tellurium exposure and garlic odour.

PubMed

Berriault, C J; Lightfoot, N E

2011-03-01

Few studies have considered garlic odour as a socially important outcome of occupational tellurium (Te) exposure or concurrent exposures, and most known guidelines focus on other signs and symptoms (e.g. weight loss and somnolence). This study considers workers exposed to tellurium and selenium (Se) at an Ontario, Canada silver refinery. To establish the relation of urinary tellurium concentrations to reporting garlic odour, while considering other work-related factors such as concurrent urinary selenium concentrations. Historical surveillance records of urinary analyses for tellurium and selenium concentrations (μmol Te or Se/mol creatinine in urine) and symptom self-reports were used. Records were available from December 1986 to June 2002. Logistic regression models were fitted using age at sampling, tellurium and selenium urine concentration and duration of employment. Individual main effects were age adjusted and the final model was fitted for tellurium and selenium urine concentration and duration of employment. Urinary tellurium concentration was significantly associated with garlic odour reporting (odds ratio = 1.74, 95% confidence interval 1.01-2.97, P < 0.05). Furthermore, the likelihood of reporting garlic odour rose as workers reached urinary tellurium concentrations >1 μmol/mol creatinine. Tellurium urinary concentrations of <1 μmol/mol creatinine appear to limit, but not eliminate, the likelihood of reporting garlic odour. Future studies should consider the effect of concurrent selenium exposure as well as other workplace factors and hygiene.

Urinary orotic acid-to-creatinine ratios in cats with hepatic lipidosis.

PubMed

VanSteenhouse, J L; Dimski, D S; Swenson, D H; Taboada, J

1999-06-01

To determine urinary orotic acid (OA) concentration and evaluate the urinary OA-to-creatinine ratio (OACR) in cats with hepatic lipidosis (HL). 20 cats with HL and 20 clinically normal cats. Hepatic lipidosis was diagnosed on the basis of clinical signs, results of serum biochemical analyses, exclusion of other concurrent illness, and cytologic or histologic evaluation of liver biopsy specimens. Urine samples were collected from each cat and frozen at -20 C until assayed. Urine creatinine concentrations were determined, using an alkaline picrate method followed by spectrophotometric assay. Urine OA concentration was determined, using high-performance liquid chromatography. Minimum amount of detectable OA in feline urine was 1 microg/ml. Because of small interfering peaks near the base of the OA peak, the minimum quantifiable concentration of OA was determined to be 5 microg/ml. Urinary OACR was compared in both groups of cats. Differences in urinary OACR were not detected between clinically normal cats and cats with HL. Peaks were not detected for urinary OA in any of the 20 clinically normal cats. Of the 20 HL cats, 14 did not have detectable peaks for urinary OA. Of the 6 HL cats that had detectable urinary OA peaks, 3 had values of <5 microg/ml. Apparently, OACR does not increase significantly in cats with HL. Urinary OACR is not a useful diagnostic test for HL in cats.

Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients.

PubMed

Seo, Ho Kyung; Kim, Sung Han; Ahn, Kyung-Ohk; Lee, Sang-Jin; Park, Weon Seo; Kim, Sohee; Hwang, Sang-Hyun; Lee, Do Hoon; Joung, Jae Young; Chung, Jinsoo; Joo, Jungnam; Jeong, Kyung-Chae

2017-11-10

Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC. We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy. Recurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC. Urine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.

Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-{alpha}) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAs{sup III}, MAs{sup V}, DMAs{sup III}, DMAs{sup V}). This study examines the relationship between TGF-{alpha} concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) frommore » areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-{alpha} in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-{alpha} concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-{alpha} levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-{alpha} concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p < 0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-{alpha} than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p = 0.003). These results suggest that TGF-{alpha} in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas.« less

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic☆

PubMed Central

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Víctor H.; Contreras-Ruiz, José; García-Vargas, Gonzalo G.; Del Razo, Luz M.

2009-01-01

Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-α) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAsIII, MAsV, DMAsIII, DMAsV). This study examines the relationship between TGF-α concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-α in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-α concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-α levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-α concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p<0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-α than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p=0.003). These results suggest that TGF-α in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas. PMID:17267001

Levels and predictors of urinary nickel concentrations of children in Germany: results from the German Environmental Survey on children (GerES IV).

PubMed

Wilhelm, Michael; Wittsiepe, Jürgen; Seiwert, Margarete; Hünken, Andreas; Becker, Kerstin; Conrad, André; Schulz, Christine; Kolossa-Gehring, Marike

2013-03-01

Human biomonitoring of nickel has gained interest in environmental medicine due to its wide distribution in the environment and its allergenic potential. There are indications that the prevalence of nickel sensitization in children is increased by nickel exposure and that oral uptake of nickel can exacerbate nickel dermatitis in nickel-sensitive individuals. Urinary nickel measurement is a good indicator of exposure. However, data on nickel levels in urine of children are rare. For the first time, the German Environmental Survey on children (GerES IV) 2003-2006 provided representative data to describe the internal nickel exposure of children aged 3-14 years in Germany. Nickel was measured after enrichment in the organic phase of urine by graphite furnace atomic absorption spectrometry with Zeeman background correction. Nickel levels (n=1576) ranged from <0.5 to 15 μg/l. Geometric mean was 1.26 μg/l. Multivariate regression analysis showed that gender, age, socio-economic status, being overweighted, consumption of hazelnut spread, nuts, cereals, chocolate and urinary creatinine were significant predictors for urinary nickel excretion of children who do not smoke. 20.2% of the variance could be explained by these variables. With a contribution of 13.8% the urinary creatinine concentration was the most important predictor. No influence of nickel intake via drinking water and second hand smoke exposure was observed. Copyright © 2012 Elsevier GmbH. All rights reserved.

Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects.

PubMed

Tang, Minghua; Larson-Meyer, D Enette; Liebman, Michael

2008-05-01

High oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. This study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. Eleven healthy subjects, aged 21-38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. Compared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. The percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.

Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls.

PubMed

Anwar, Attia; Marini, Marina; Abruzzo, Provvidenza Maria; Bolotta, Alessandra; Ghezzo, Alessandro; Visconti, Paola; Thornalley, Paul J; Rabbani, Naila

2016-11-01

To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage. 27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined. Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower-upper quartile]): autistic children - 6.60 nM (4.48-8.91) and 7.00 nM (5.51-8.55), and healthy controls - 6.82 nM (4.47-7.02) and 6.82 nM (5.84-8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81-8.52) versus 9.00 nM (8.41-10.71), p < .01. Urinary excretion of thiamine and fractional renal clearance of thiamine did not change between the groups. No correlation was observed between clinical markers and the plasma and urine thiamine concentration. Plasma protein dityrosine content was increased 88% in ASD. Other oxidative markers were unchanged. Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased. The latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation. Increased plasma protein dityrosine may reflect increased dual oxidase activity in response to change in mucosal immunity and host-microbe homeostasis.

[Iodine concentration in cooking salt consumed in Lubumbashi and the iodine status of vulnerable people: case study of pregnant women living in underprivileged areas].

PubMed

Banza, Bienvenue Ilunga; Lumbu, Jean Baptiste Simbi; Donnen, Philippe; Twite, Eugène Kabange; Kwete, Daniel Mikobi; Kazadi, Costa Mwadianvita; Ozoza, Jean Okolonken; Habimana, Laurence; Kalenga, Prosper Muenze Kayamba; Robert, Annie

2016-01-01

Consumption of low iodine salt can cause different types of disorders associated with iodine deficiency. This study aims to determine iodine content in table salt consumed in Lubumbashi and iodine status of pregnant women who are the main target of iodine deficiency. aAdescriptive cross-sectional study was devoted to an iodometric iodine analysis of 739 salt samples collected from the households and the markets of Lubumbashi in 2014. Previously, urinary iodine concentrations were determined in 225 pregnant women received for consultation from 15 March 2009 to 25 April 2011 by mineralization technique using ammonium persulphate. Our survey found that 47.5% of the cooking salt samples were adequately iodized (from 15 to 40 ppm), 36,9% of the samples had low iodine levels, 7,4% of the samples had too much iodine and 8,1% of the samples were not iodized. Iodine concentration in the analyzed cooking salt reached an overall average of 54,9%, being clearly below the WHO Standards (90%). By measuring urinary iodine concentration of pregnant women, iodine deficiency (urinary iodine <150 µg/l) was observed in 52%. The low availability of iodine from consumed salt in Lubumbashi could be responsible for a large proportion of the observed iodine deficiency in pregnant women, exposing them to the major risks for disorders associated with iodine deficiency.

Fructo-Oligosaccharide (DFA III) Feed Supplementation for Mitigation of Mycotoxin Exposure in Cattle-Clinical Evaluation by a Urinary Zearalenone Monitoring System.

PubMed

Toda, Katsuki; Uno, Seiichi; Kokushi, Emiko; Shiiba, Ayaka; Hasunuma, Hiroshi; Matsumoto, Daisaku; Ohtani, Masayuki; Yamato, Osamu; Shinya, Urara; Wijayagunawardane, Missaka; Fink-Gremmels, Johanna; Taniguchi, Masayasu; Takagi, Mitsuhiro

2018-06-01

The potential effect of difructose anhydride III (DFA III) supplementation in cattle feed was evaluated using a previously developed urinary-zearalenone (ZEN) monitoring system. Japanese Black cattle from two beef herds aged 9⁻10 months were used. DFA III was supplemented for two weeks. ZEN concentrations in feed were similar in both herds (0.27 and 0.22 mg/kg in roughage and concentrates, respectively), and below the maximum allowance in Japan. ZEN, α-zearalenol (α-ZOL), and β-ZOL concentrations in urine were measured using LC/MS/MS the day before DFA III administration, 9 and 14 days thereafter, and 9 days after supplementation ceased. Significant differences in ZEN, α-ZOL, β-ZOL, and total ZEN were recorded on different sampling dates. The concentration of inorganic phosphate in DFA III-supplemented animals was significantly higher than in controls on day 23 (8.4 vs. 7.7 mg/dL), suggesting a possible role of DFA III in tight junction of intestinal epithelial cells. This is the first evidence that DFA III reduces mycotoxin levels reaching the systemic circulation and excreted in urine. This preventive effect may involve an improved tight-junction-dependent intestinal barrier function. Additionally, our practical approach confirmed that monitoring of urinary mycotoxin is useful for evaluating the effects of dietary supplements to prevent mycotoxin adsorption.

Biomarkers of mercury exposure at a mercury recycling facility in Ukraine.

PubMed

Gibb, Herman Jones; Kozlov, Kostj; Buckley, Jessie Poulin; Centeno, Jose; Jurgenson, Vera; Kolker, Allan; Conko, Kathryn; Landa, Edward; Panov, Boris; Panov, Yuri; Xu, Hanna

2008-08-01

This study evaluates biomarkers of occupational mercury exposure among workers at a mercury recycling operation in Gorlovka, Ukraine. The 29 study participants were divided into three occupational categories for analysis: (1) those who worked in the mercury recycling operation (Group A, n = 8), (2) those who worked at the facility but not in the yard where the recycling was done (Group B, n = 14), and (3) those who did not work at the facility (Group C, n = 7). Urine, blood, hair, and nail samples were collected from the participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in the former mercury mine/smelter located on the site of the recycling facility. Each factor was tested in a univariate regression with total mercury in urine, blood, hair, and nails. Median biomarker concentrations were 4.04 microg/g-Cr (urine), 2.58 microg/L (blood), 3.95 microg/g (hair), and 1.16 microg/g (nails). Occupational category was significantly correlated (p < 0.001) with both blood and urinary mercury concentrations but not with hair or nail mercury. Four individuals had urinary mercury concentrations in a range previously found to be associated with subtle neurological and subjective symptoms (e.g., fatigue, loss of appetite, irritability), and one worker had a urinary mercury concentration in a range associated with a high probability of neurological effects and proteinuria. Comparison of results by occupational category found that workers directly involved with the recycling operation had the highest blood and urinary mercury levels. Those who worked at the facility but were not directly involved with the recycling operation had higher levels than those who did not work at the facility.

Changes in Urinary Bisphenol A Concentrations Associated with Placement of Dental Composite Restorations in Children and Adolescents

PubMed Central

Maserejian, Nancy N.; Trachtenberg, Felicia L.; Wheaton, Olivia Brown; Calafat, Antonia M.; Ranganathan, Gayatri; Kim, Hae-Young; Hauser, Russ

2016-01-01

Background BisGMA-based dental composites may release bisphenol A (BPA). Our purpose was to assess changes in urinary BPA concentrations over 6-months follow-up in children and adolescents receiving bisGMA-based restorations. Methods We collected urine and interviewed parents/guardians for BPA-related exposure information before and approximately one-day, 14-days, and 6-months post-treatment among 91 participants aged 3–17 years needing composite restorations. We used multivariable linear regression models to test associations between number of surface-restorations placed and changes in urinary BPA concentrations. Results Participants had on average 1.4 (sd=1.0) surfaces filled with composite at the first treatment visit and a cumulative 2.3 (sd=1.6) surfaces filled during the study. Mean change in BPA between pretreatment and next-day was 1.71 ng/mL (sd=9.94) overall and 0.87 (sd=5.98) after excluding one participant with 8 surfaces filled at the visit. Overall, a greater number of composite surface-restorations placed was associated with higher BPA in the next-day sample (posterior-occlusal eβ=1.47, 95% CI 1.18–1.83; P<0.001), but this was attenuated after restricting to the 88 participants with ≤4 fillings (eβ=1.19, 95% CI 0.86, 1.64), and no association was observed using 14-day (eβ=0.94, 95% CI 0.75–1.18) or 6- month (eβ=0.88, 95% CI 0.74–1.04) samples. Conclusions Placement of bisGMA-based restorations in children and adolescents may produce transient increases in urinary BPA concentration, which are no longer detectable approximately 14-days or 6-months post-treatment in urine samples. When few restorations are placed, increases in urinary BPA concentrations may not be detectable owing to high inter-individual variation in BPA exposure. Practical Implications These results suggest that leaching of BPA from newly placed composites ceases being detectable in urine within 2 weeks of restoration placement. The potential human health impact of such short-term exposure remains uncertain. PMID:27083778

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribedburn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changes inmore » urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changesmore » in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2008-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh.

PubMed

Rodrigues, Ema G; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C

2012-05-01

We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individuals without skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid urinary concentrations, whereas wild-type AS3MT rs11191439 had significantly lower levels of As(III) and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion.

Association between Secondhand Smoke in Hospitality Venues and Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol Concentrations in Non-Smoking Staff.

PubMed

Kim, Jeonghoon; Lee, Kiyoung; Kwon, Ho-Jang; Lee, Do Hoon; Kim, KyooSang

2016-11-08

The purpose of this study was to determine the relationship between urinary cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations in non-smoking staff and the indoor levels of fine particles (PM 2.5 ) in hospitality venues that allow smoking, with respect to demographic and indoor environmental factors. We evaluated 62 hospitality venues that allowed smoking in Seoul, Korea. A real-time aerosol monitor was used to measure indoor PM 2.5 concentrations. Field technicians recorded indoor environmental characteristics. One non-smoking staff member in each hospitality venue was tested for urinary cotinine and total NNAL concentrations. Demographic characteristics were obtained from self-reported staff questionnaires. Natural-log (ln)-transformed PM 2.5 concentrations were significantly correlated with the ln-transformed cotinine ( r = 0.31) and the total NNAL concentrations ( r = 0.32). In multivariable regression analysis, the urinary cotinine concentrations of the staff members were significantly correlated with indoor PM 2.5 concentrations; those with the highest concentrations were more likely to be women or staff members that worked in venues with a volume <375 m³. Total NNAL concentrations were significantly correlated only with indoor PM 2.5 concentrations. Indoor PM 2.5 may be used as an indicator for urinary cotinine and total NNAL concentrations in non-smoking staff members in hospitality venues that allow smoking.

Association between Secondhand Smoke in Hospitality Venues and Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol Concentrations in Non-Smoking Staff

PubMed Central

Kim, Jeonghoon; Lee, Kiyoung; Kwon, Ho-Jang; Lee, Do Hoon; Kim, KyooSang

2016-01-01

The purpose of this study was to determine the relationship between urinary cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations in non-smoking staff and the indoor levels of fine particles (PM2.5) in hospitality venues that allow smoking, with respect to demographic and indoor environmental factors. We evaluated 62 hospitality venues that allowed smoking in Seoul, Korea. A real-time aerosol monitor was used to measure indoor PM2.5 concentrations. Field technicians recorded indoor environmental characteristics. One non-smoking staff member in each hospitality venue was tested for urinary cotinine and total NNAL concentrations. Demographic characteristics were obtained from self-reported staff questionnaires. Natural-log (ln)-transformed PM2.5 concentrations were significantly correlated with the ln-transformed cotinine (r = 0.31) and the total NNAL concentrations (r = 0.32). In multivariable regression analysis, the urinary cotinine concentrations of the staff members were significantly correlated with indoor PM2.5 concentrations; those with the highest concentrations were more likely to be women or staff members that worked in venues with a volume <375 m3. Total NNAL concentrations were significantly correlated only with indoor PM2.5 concentrations. Indoor PM2.5 may be used as an indicator for urinary cotinine and total NNAL concentrations in non-smoking staff members in hospitality venues that allow smoking. PMID:27834821

Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

PubMed Central

Fernández-Repollet, E; Martínez-Maldonado, M; Opava-Stitzer, S

1980-01-01

1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic condition. PMID:7441565

Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.

PubMed

Hara, Fumihiko; Tatebe, Junko; Watanabe, Ippei; Yamazaki, Junichi; Ikeda, Takanori; Morita, Toshisuke

2016-08-25

Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated β-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs. H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).

Comparison of the Health Implications on the Use of As and Cd Contaminated Water Supply between Urban and Rural Communities

PubMed Central

Zailina, H.; Najibah, H.; Nadia Aiezzati, A.; Praveena, S. M.; Patimah, I.

2014-01-01

A cross-sectional study was carried out to determine the arsenic (As) and cadmium (Cd) concentrations in blood, urine, and drinking water as well as the health implications on 100 residents in an urban and a rural community. Results showed the blood As, urinary Cd, DNA damage, and water As and Cs were significantly (P < 0.001) higher in the rural community. Findings showed significant (P < 0.005) correlations between blood As and DNA damage with household income, years of residence, and total glasses of daily water consumption among the rural residents. The urinary NAG concentrations, years of residence, milk powder intake (glass/week), and seafood intake (per week) were significantly correlated (P < 0.005) with urinary Cd concentrations among respondents. In addition, urinary Cd level significantly influenced the urinary NAG concentrations (P < 0.001). The rural respondents experienced significantly higher lymphocyte DNA damage and blood As influenced by their years of residence and water consumption. The Cd in drinking water also resulted in the rural respondents having significantly higher urinary NAG which had a significant relationship with urinary Cd. PMID:25530970

Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study

PubMed Central

2012-01-01

Background Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt. Methods We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure. Results Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA. Conclusions Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles. PMID:22472083

Preeclampsia and toxic metals: a case-control study in Kinshasa, DR Congo.

PubMed

Elongi Moyene, Jean-Pierre; Scheers, Hans; Tandu-Umba, Barthélémy; Haufroid, Vincent; Buassa-Bu-Tsumbu, Baudouin; Verdonck, Fons; Spitz, Bernard; Nemery, Benoit

2016-04-05

Preeclampsia is frequent in Kinshasa (Democratic Republic of Congo), especially during the dry season. We tested whether preeclampsia was associated with exposure to environmental metals. Using a case-control design, 88 women hospitalized with preeclampsia (cases) and 88 healthy pregnant women from the antenatal clinic (controls) were included in the study; 67 and 109 women were enrolled during the rainy and dry season, respectively. The concentrations of 24 elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS) in 24-h urine collections. Differences in the urinary excretion of metals were investigated between cases and controls, and the interaction with season was assessed. Cases and controls were well matched regarding age, parity and duration of pregnancy. In controls, the urinary concentrations of most elements were substantially higher than reference values for adults from industrially developed countries, e.g. for lead: geometric mean (GM) 8.0 μg/L [25(th)-75(th) percentile 3.1-13.8]. The daily urinary excretions of 14 metals were significantly higher in women with preeclampsia than in control women, e.g. for lead: GM 61 μg/day (25(th)-75(th) percentile 8-345) in women with preeclampsia vs 9 μg/day (25(th)-75(th) percentile 3-21) in controls (p < 0.001). A significant interaction was found between season and preeclampsia for several elements, with higher urinary excretions in preeclamptic women than controls during the dry season, but not during the rainy season. This study revealed not only that women with preeclampsia excrete higher amounts of several toxic metals, especially lead, than control women, but also that this excretion exhibits seasonal variation, thus possibly explaining the high incidence and seasonal variation of preeclampsia in Kinshasa. Although the exact sources of this exposure are unknown, these findings underscore the need for preventing environmental exposures to lead and other toxic metals.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer.

PubMed

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-10-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer

PubMed Central

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-01-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer. PMID:28943911

Estimating 24-Hour Urinary Sodium Excretion From Casual Urinary Sodium Concentrations in Western Populations

PubMed Central

Brown, Ian J.; Dyer, Alan R.; Chan, Queenie; Cogswell, Mary E.; Ueshima, Hirotsugu; Stamler, Jeremiah; Elliott, Paul

2013-01-01

High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984–1987 at the ages of 20–59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were −1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and −1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity. PMID:23673246

Arterial stiffness and sedentary lifestyle: Role of oxidative stress.

PubMed

Lessiani, Gianfranco; Santilli, Francesca; Boccatonda, Andrea; Iodice, Pierpaolo; Liani, Rossella; Tripaldi, Romina; Saggini, Raoul; Davì, Giovanni

2016-04-01

Sedentary lifestyle is a risk factor for the development of cardiovascular disease, and leads to a quantifiable impairment in vascular function and arterial wall stiffening. We tested the hypothesis of oxidative stress as a determinant of arterial stiffness (AS) in physically inactive subjects, and challenged the reversibility of these processes after the completion of an eight-week, high-intensity exercise training (ET). AS was assessed before and after ET, measuring carotid to femoral pulse wave velocity (PWV) with a Vicorder device. At baseline and after ET, participants performed urine collection and underwent fasting blood sampling. Urinary 8-iso-PGF2α, an in vivo marker of lipid peroxidation, total, HDL and LDL cholesterol, and triglyceride concentrations were measured. ET was associated with significantly reduced urinary 8-iso-PGF2α(p<0.0001) levels. PWV was significantly reduced after ET completion (p<0.0001), and was directly related to urinary 8-iso-PGF2α(Rho=0.383, p=0.021). After ET, cardiovascular fitness improved [peak oxygen consumption (p<0.0001), peak heart rate (p<0.0001)]. However, no improvement in lipid profile was observed, apart from a significant reduction of triglycerides (p=0.022). PWV and triglycerides were significantly related (Rho=0.466, p=0.005) throughout the study period. PWV levels were also related to urinary 8-iso-PGF2α in our previously sedentary subjects. We conclude that regular physical exercise may be a natural antioxidant strategy, lowering oxidant stress and thereby the AS degree. Copyright © 2015 Elsevier Inc. All rights reserved.

Urinary biomarkers in hydronephrosis.

PubMed

Madsen, Mia Gebauer

2013-02-01

Hydronephrosis is diagnosed in 0.5-1% of all newborns, and ureteropelvic junction obstruction (UPJO) accounts for 35% of those cases. A urinary tract obstruction that occurs during early kidney development affects renal morphogenesis, maturation, and growth, and in the most severe cases, this will ultimately lead to progressive renal tubular atrophy and interstitial fibrosis with the loss of nephrons. The clinical management of these patients remains a controversial topic. The aim is to preserve renal function by identifying the 15-20% of children who require early surgical intervention from those for whom watchful waiting may be appropriate because of spontaneous resolving/stabilization without significant loss of renal function. Although the patients attend regular follow-ups, including repetitive blood tests, ultrasonographies, and the more invasive diuretic renograms, the surgeons still miss reliably biomarkers that could be used as predictors for renal parenchymal damage and decreased renal function, and thereby provide more clear indications for surgical intervention. The aim of this PhD thesis was to further elucidate the pathophysiology of obstructive nephropathy (study I) and to search for potential candidate biomarkers that may have a predictive and/or diagnostic value in the management of hydronephrosis (study II). Study I: Urine and kidney cytokine profiles in experimental unilateral acute and chronic hydronephrosis. To study the dynamics of the urinary secretion of cytokines after the release of unilateral ureteral obstruction, and to study whether the urinary concentrations of these compounds reliably reflects changes in the renal parenchyma. This was tested in 2 experimental rat models: an acute obstruction model and a chronic obstruction model. The acute obstruction model demonstrated significant differences in the renal levels of IL-1β, IL-6, TNF-α, and IL-10 in comparison with controls, and these differences were associated with similar differences in their urinary excretion. Such results were not obtained in the chronic obstruction model in which significant differences were only demonstrated in the urinary concentrations of IL-6. Study II: Candidate urinary biomarkers in hydronephrosis - a clinical study. To study the dynamics of the urinary excretion of selected potential biomarkers in children after the relief of UPJO, and to compare their findings with healthy controls. Twenty-eight children with UPJO were included in the study from 2007-2011 together with 13 healthy children. Pre-, peri- and post-operatively (1 year) urine samples were collected. The median age of the patients was 8.1 (3.5-14.5) years. Five proteins (EGF, IP-10, MCP-1, RANTES, and MIP-1α) were examined in study IIa, and 4 proteins (NGAL, CyC, βM-2, and OPN) were examined in study IIb. In brief, significantly increased urinary concentrations of EGF and MCP-1 were demonstrated in children with UPJO compared to controls, which was followed by a decline in the post-operative period to levels similar to the controls. This indicates that the urinary concentrations of EGF and MCP-1 are regulated as a response to the obstruction, suggesting that they may have a potential as urinary biomarkers in hydronephrosis. In general, urine from the obstructed kidney exhibited higher concentrations of the proteins compared to urine from the nonobstructed kidney. Furthermore, CyC, β-2M, and OPN were negatively correlated with age, and IP-10 and MCP-1 were negatively correlated with DRF. In conclusion, this PhD study confirmed increased concentrations of selected proteins in urine from kidneys suffering from obstruction. Interestingly, it was observed that some urinary proteins had an age-dependent excretion. Further investigations are required to test the ability of the examined proteins to identify an obstruction and reveal disease progression and, thereby, be useful clinical tools.

EVALUATION AND COMPARISON OF URINARY METABOLIC BIOMARKERS OF EXPOSURE FOR THE JET FUEL JP-8

PubMed Central

B’Hymer, Clayton; Krieg, Edward; Cheever, Kenneth L.; Toennis, Christine A.; Clark, John C.; Kesner, James S.; Gibson, Roger; Butler, Mary Ann

2015-01-01

A study of workers exposed to jet fuel propellant 8 (JP-8) was conducted at U.S. Air Force bases and included the evaluation of three biomarkers of exposure: S-benzylmercapturic acid (BMA), S-phenylmercapturic acid (PMA), and (2-methoxyethoxy)acetic acid (MEAA). Postshift urine specimens were collected from various personnel categorized as high (n = 98), moderate (n = 38) and low (n = 61) JP-8 exposure based on work activities. BMA and PMA urinary levels were determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), and MEAA urinary levels were determined by gas chromatography–mass spectrometry (GC-MS). The numbers of samples determined as positive for the presence of the BMA biomarker (above the test method’s limit of detection [LOD = 0.5 ng/ml]) were 96 (98.0%), 37 (97.4%), and 58 (95.1%) for the high, moderate, and low (control) exposure workgroup categories, respectively. The numbers of samples determined as positive for the presence of the PMA biomarker (LOD = 0.5 ng/ml) were 33 (33.7%), 9 (23.7%), and 12 (19.7%) for the high, moderate, and low exposure categories. The numbers of samples determined as positive for the presence of the MEAA biomarker (LOD = 0.1 μg/ml) were 92 (93.4%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure categories. Statistical analysis of the mean levels of the analytes demonstrated MEAA to be the most accurate or appropriate biomarker for JP-8 exposure using urinary concentrations either adjusted or not adjusted for creatinine; mean levels of BMA and PMA were not statistically significant between workgroup categories after adjusting for creatinine. PMID:22712851

Evaluation and comparison of urinary metabolic biomarkers of exposure for the jet fuel JP-8.

PubMed

B'Hymer, Clayton; Krieg, Edward; Cheever, Kenneth L; Toennis, Christine A; Clark, John C; Kesner, James S; Gibson, Roger; Butler, Mary Ann

2012-01-01

A study of workers exposed to jet fuel propellant 8 (JP-8) was conducted at U.S. Air Force bases and included the evaluation of three biomarkers of exposure: S-benzylmercapturic acid (BMA), S-phenylmercapturic acid (PMA), and (2-methoxyethoxy)acetic acid (MEAA). Postshift urine specimens were collected from various personnel categorized as high (n = 98), moderate (n = 38) and low (n = 61) JP-8 exposure based on work activities. BMA and PMA urinary levels were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and MEAA urinary levels were determined by gas chromatography-mass spectrometry (GC-MS). The numbers of samples determined as positive for the presence of the BMA biomarker (above the test method's limit of detection [LOD = 0.5 ng/ml]) were 96 (98.0%), 37 (97.4%), and 58 (95.1%) for the high, moderate, and low (control) exposure workgroup categories, respectively. The numbers of samples determined as positive for the presence of the PMA biomarker (LOD = 0.5 ng/ml) were 33 (33.7%), 9 (23.7%), and 12 (19.7%) for the high, moderate, and low exposure categories. The numbers of samples determined as positive for the presence of the MEAA biomarker (LOD = 0.1 μ g/ml) were 92 (93.4%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure categories. Statistical analysis of the mean levels of the analytes demonstrated MEAA to be the most accurate or appropriate biomarker for JP-8 exposure using urinary concentrations either adjusted or not adjusted for creatinine; mean levels of BMA and PMA were not statistically significant between workgroup categories after adjusting for creatinine.

Urinary Trivalent Methylated Arsenic Species in a Population Chronically Exposed to Inorganic Arsenic

PubMed Central

Valenzuela, Olga L.; Borja-Aburto, Victor H.; Garcia-Vargas, Gonzalo G.; Cruz-Gonzalez, Martha B.; Garcia-Montalvo, Eliud A.; Calderon-Aranda, Emma S.; Del Razo, Luz M.

2005-01-01

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs–exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis. PMID:15743710

Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults.

PubMed

Lang, Iain A; Galloway, Tamara S; Scarlett, Alan; Henley, William E; Depledge, Michael; Wallace, Robert B; Melzer, David

2008-09-17

Bisphenol A (BPA) is widely used in epoxy resins lining food and beverage containers. Evidence of effects in animals has generated concern over low-level chronic exposures in humans. To examine associations between urinary BPA concentrations and adult health status. Cross-sectional analysis of BPA concentrations and health status in the general adult population of the United States, using data from the National Health and Nutrition Examination Survey 2003-2004. Participants were 1455 adults aged 18 through 74 years with measured urinary BPA and urine creatinine concentrations. Regression models were adjusted for age, sex, race/ethnicity, education, income, smoking, body mass index, waist circumference, and urinary creatinine concentration. The sample provided 80% power to detect unadjusted odds ratios (ORs) of 1.4 for diagnoses of 5% prevalence per 1-SD change in BPA concentration, or standardized regression coefficients of 0.075 for liver enzyme concentrations, at a significance level of P < .05. Chronic disease diagnoses plus blood markers of liver function, glucose homeostasis, inflammation, and lipid changes. Higher urinary BPA concentrations were associated with cardiovascular diagnoses in age-, sex-, and fully adjusted models (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.18-1.63; P = .001 with full adjustment). Higher BPA concentrations were also associated with diabetes (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.21-1.60; P < .001) but not with other studied common diseases. In addition, higher BPA concentrations were associated with clinically abnormal concentrations of the liver enzymes gamma-glutamyltransferase (OR per 1-SD increase in BPA concentration, 1.29; 95% CI, 1.14-1.46; P < .001) and alkaline phosphatase (OR per 1-SD increase in BPA concentration, 1.48; 95% CI, 1.18-1.85; P = .002). Higher BPA exposure, reflected in higher urinary concentrations of BPA, may be associated with avoidable morbidity in the community-dwelling adult population.

In vivo measurement of human body composition

NASA Technical Reports Server (NTRS)

Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Price, D. C.

1974-01-01

The female bed rest study has shown that, the response of women to prolonged recumbency of 2 to 3 weeks duration is very similar to that displayed by men. Some of the key findings in the women after 17 days of continuous recumbency are: (1) a decrease in plasma volume of 12-13 per cent; (2) a small decrease in total body water; (3) a decrease in total body potassium of 3 to 4 per cent; (4) a decrease in plasma potassium concentration of 4 to 5 per cent; (5) a decrease in total circulating plasma protein of 11 to 12 per cent; (6) a decrease in urinary norepinephrine excretion rate of 27 to 28 per cent; (7) a possible increase in urinary magnesium, calcium, and phosphate excretion rates; and (8) a possible increase in urinary citrate excretion rate.

The protective effect of clavulanic acid in a combined formulation on the concentration of amoxycillin in the urine of patients with urinary tract infections.

PubMed

Lindeque, K P

1982-07-28

Three paraplegic patients with urinary tract infections caused by a beta-lactamase-producing Klebsiella pneumoniae were treated with a combination of amoxycillin and clavulanic acid (A-CA) (Augmentin; Beecham), after initial and unsuccessful therapy with amoxycillin alone. The administration of A-CA resulted in a rapid decrease in the urinary bacterial cell count, coupled with a dramatic increase in urinary amoxycillin concentrations.

Failure of catalase to protect against aflatoxin B{sub 1}-induced mouse lung tumorigenicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guindon, Katherine A.; Foley, Julie F.; Maronpot, Robert R.

The carcinogenic mycotoxin aflatoxin B{sub 1} (AFB{sub 1}) induces 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in mouse lung, an effect that can be prevented by treatment with polyethylene glycol-conjugated catalase (PEG-CAT). G {yields} T transversion mutation in K-ras, an early event in AFB{sub 1}-induced mouse lung carcinogenesis, is thought to result from AFB{sub 1}-8,9-exo-epoxide binding to DNA to form AFB{sub 1}-N{sup 7}-guanine, but may also result from formation of 8-OHdG. Therefore, oxidative DNA damage may be important in AFB{sub 1} carcinogenicity. The objective of this study was to determine whether PEG-CAT would prevent AFB{sub 1} tumorigenicity. Mouse lung tumorigenesis was assessed following treatmentmore » of female A/J mice with 300 kU/kg PEG-CAT ip and/or 50 mg/kg AFB{sub 1}. Mice were killed 7 months post-treatment and tumors greater than 1 mm in diameter were excised. Unexpectedly, the mean number of tumors per mouse in the PEG-CAT + AFB{sub 1} group (8.81 {+-} 3.64, n = 47) was greater than that of the group treated with AFB{sub 1} alone (7.05 {+-} 3.45, n = 42) (P < 0.05). The tumors obtained from mice treated with PEG-CAT + AFB{sub 1} were larger than those from mice treated with AFB{sub 1} alone (P < 0.05). There was no difference in K-ras exon 1 mutation spectrum or in the histological diagnosis of tumors between AFB{sub 1} and PEG-CAT + AFB{sub 1} groups (P > 0.05). In vitro incubation with mouse liver catalase (CAT) resulted in conversion of [{sup 3}H]AFB{sub 1} into a DNA-binding species, a possible explanation for the results observed in vivo. These results demonstrate that PEG-CAT is not protective against AFB{sub 1} carcinogenicity in mouse lung despite preventing DNA oxidation.« less

Hypoglycemic Effect of Lipoic Acid, Carnitine and Nigella Sativa in Diabetic Rat Model

PubMed Central

Salama, Ragaa Hamdy Mohamed

2011-01-01

Objectives Evaluation of therapeutic potentials of α-lipoic acid (α-LA), L-carnitine, Nigella sativa (N. sativa) or combination of them in carbohydrate and lipid metabolism of DM type I. Methods Rat model of diabetes was induced by single i.p injection of Streptozocin (STZ) 65 mg/kg. The rats were randomly assigned to 6 groups (G): healthy reference (HR), diabetic (DM), DM treated with α-lipoic acid, DM treated with L-carnitine, DM treated with N. sativa, and DM treated with combination of the 3 compounds. After 30 days from onset of diabetes, serum and tissue homogenate were obtained for evaluation of glucose metabolism as fasting blood glucose, insulin, insulin sensitivity, HOMA, C-peptide, and pyruvate dehydrogenase (PDH) activity. For lipid metabolism evaluation, total cholesterol and triacylglycerol (TG) were determined. Markers of antioxidants and oxidative status as total antioxidant capacity (TAC), glutathione-S-transeferase (GST), 8-hydroxy-2-deoxyguanosine (8-OH-dG) were measured. Results Either α-LA or N. sativa significantly reduced the elevated blood glucose level. The combination of 3 compounds significantly increased the level of insulin and C-peptide. Also, increased the antioxidant activity measured by TAC and decreased the oxidative damage of DNA as measured by 8-OH-dG. HOMA- β increased in G3 and G6 compared to G2. However, the decrease in TG, and total cholesterol levels were non-significant in all groups. Conclusion Combination of α-LA, L-carnitine and N. sativa will contribute significantly in improvement of the carbohydrate metabolism and to less extent lipid metabolism in diabetic rats, thus increasing the rate of success in management of DM. Also, this combination will have implications in clinical studies and clinical applications. PMID:23267290

Hypoglycemic effect of lipoic Acid, carnitine and nigella sativa in diabetic rat model.

PubMed

Salama, Ragaa Hamdy Mohamed

2011-07-01

Evaluation of therapeutic potentials of α-lipoic acid (α-LA), L-carnitine, Nigella sativa (N. sativa) or combination of them in carbohydrate and lipid metabolism of DM type I. Rat model of diabetes was induced by single i.p injection of Streptozocin (STZ) 65 mg/kg. The rats were randomly assigned to 6 groups (G): healthy reference (HR), diabetic (DM), DM treated with α-lipoic acid, DM treated with L-carnitine, DM treated with N. sativa, and DM treated with combination of the 3 compounds. After 30 days from onset of diabetes, serum and tissue homogenate were obtained for evaluation of glucose metabolism as fasting blood glucose, insulin, insulin sensitivity, HOMA, C-peptide, and pyruvate dehydrogenase (PDH) activity. For lipid metabolism evaluation, total cholesterol and triacylglycerol (TG) were determined. Markers of antioxidants and oxidative status as total antioxidant capacity (TAC), glutathione-S-transeferase (GST), 8-hydroxy-2-deoxyguanosine (8-OH-dG) were measured. Either α-LA or N. sativa significantly reduced the elevated blood glucose level. The combination of 3 compounds significantly increased the level of insulin and C-peptide. Also, increased the antioxidant activity measured by TAC and decreased the oxidative damage of DNA as measured by 8-OH-dG. HOMA- β increased in G3 and G6 compared to G2. However, the decrease in TG, and total cholesterol levels were non-significant in all groups. Combination of α-LA, L-carnitine and N. sativa will contribute significantly in improvement of the carbohydrate metabolism and to less extent lipid metabolism in diabetic rats, thus increasing the rate of success in management of DM. Also, this combination will have implications in clinical studies and clinical applications.

Long-term indoor air conditioner filtration and cardiovascular health: A randomized crossover intervention study.

PubMed

Chuang, Hsiao-Chi; Ho, Kin-Fai; Lin, Lian-Yu; Chang, Ta-Yuan; Hong, Gui-Bing; Ma, Chi-Ming; Liu, I-Jung; Chuang, Kai-Jen

2017-09-01

The association of short-term air pollution filtration with cardiovascular health has been documented. However, the effect of long-term indoor air conditioner filtration on the association between air pollution and cardiovascular health is still unclear. We recruited 200 homemakers from Taipei and randomly assigned 100 of them to air filtration or control intervention; six home visits were conducted per year from 2013 to 2014. The participants under air filtration intervention during 2013 were reassigned to control intervention in 2014. The air pollution measurements consisted of particulate matter less than or equal to 2.5μm in diameter (PM 2.5 ) and total volatile organic compounds (VOCs); blood pressure was monitored for each participant during each visit. The following morning, blood samples were collected after air pollution monitoring. The blood samples were used to analyze biological markers, including high sensitivity-C-reactive protein (hs-CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and fibrinogen. Household information, including cleaning, cooking, and air conditioning, was collected by a questionnaire. Mixed-effects models were used to investigate the associations among air pollution measurements, blood pressure and biological markers. The results showed that increased levels of PM 2.5 and total VOCs were associated with increased hs-CRP, 8-OHdG and blood pressure. The health variables were higher among participants in the control intervention phase than among those in the air filtration intervention phase. We concluded that air pollution exposure was associated with systemic inflammation, oxidative stress and elevated blood pressure. The long-term filtration of air pollution with an air conditioner filter was associated with cardiovascular health of adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative Stress and Mitochondrial Functions in the Intestinal Caco-2/15 Cell Line

PubMed Central

Taha, Rame; Seidman, Ernest; Mailhot, Genevieve; Boudreau, François; Gendron, Fernand-Pierre; Beaulieu, Jean-François; Ménard, Daniel; Delvin, Edgard; Amre, Devendra; Levy, Emile

2010-01-01

Background Although mitochondrial dysfunction and oxidative stress are central mechanisms in various pathological conditions, they have not been extensively studied in the gastrointestinal tract, which is known to be constantly exposed to luminal oxidants from ingested foods. Key among these is the simultaneous consumption of iron salts and ascorbic acid, which can cause oxidative damage to biomolecules. Methodology/Principal Findings The objective of the present work was to evaluate how iron-ascorbate (FE/ASC)-mediated lipid peroxidation affects mitochondrion functioning in Caco-2/15 cells. Our results show that treatment of Caco-2/15 cells with FE/ASC (0.2 mM/2 mM) (1) increased malondialdehyde levels assessed by HPLC; (2) reduced ATP production noted by luminescence assay; (3) provoked dysregulation of mitochondrial calcium homeostasis as evidenced by confocal fluorescence microscopy; (4) upregulated the protein expression of cytochrome C and apoptotic inducing factor, indicating exaggerated apoptosis; (5) affected mitochondrial respiratory chain complexes I, II, III and IV; (6) elicited mtDNA lesions as illustrated by the raised levels of 8-OHdG; (7) lowered DNA glycosylase, one of the first lines of defense against 8-OHdG mutagenicity; and (8) altered the gene expression and protein mass of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2) without any effects on RNA Polymerase. The presence of the powerful antioxidant BHT (50 µM) prevented the occurrence of oxidative stress and most of the mitochondrial abnormalities. Conclusions/Significance Collectively, our findings indicate that acute exposure of Caco-2/15 cells to FE/ASC-catalyzed peroxidation produces harmful effects on mitochondrial functions and DNA integrity, which are abrogated by the powerful exogenous BHT antioxidant. Functional derangements of mitochondria may have implications in oxidative stress-related disorders such as inflammatory bowel diseases. PMID:20676402

Oxidative stress and mitochondrial functions in the intestinal Caco-2/15 cell line.

PubMed

Taha, Rame; Seidman, Ernest; Mailhot, Genevieve; Boudreau, François; Gendron, Fernand-Pierre; Beaulieu, Jean-François; Ménard, Daniel; Delvin, Edgard; Amre, Devendra; Levy, Emile

2010-07-27

Although mitochondrial dysfunction and oxidative stress are central mechanisms in various pathological conditions, they have not been extensively studied in the gastrointestinal tract, which is known to be constantly exposed to luminal oxidants from ingested foods. Key among these is the simultaneous consumption of iron salts and ascorbic acid, which can cause oxidative damage to biomolecules. The objective of the present work was to evaluate how iron-ascorbate (FE/ASC)-mediated lipid peroxidation affects mitochondrion functioning in Caco-2/15 cells. Our results show that treatment of Caco-2/15 cells with FE/ASC (0.2 mM/2 mM) (1) increased malondialdehyde levels assessed by HPLC; (2) reduced ATP production noted by luminescence assay; (3) provoked dysregulation of mitochondrial calcium homeostasis as evidenced by confocal fluorescence microscopy; (4) upregulated the protein expression of cytochrome C and apoptotic inducing factor, indicating exaggerated apoptosis; (5) affected mitochondrial respiratory chain complexes I, II, III and IV; (6) elicited mtDNA lesions as illustrated by the raised levels of 8-OHdG; (7) lowered DNA glycosylase, one of the first lines of defense against 8-OHdG mutagenicity; and (8) altered the gene expression and protein mass of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2) without any effects on RNA Polymerase. The presence of the powerful antioxidant BHT (50 microM) prevented the occurrence of oxidative stress and most of the mitochondrial abnormalities. Collectively, our findings indicate that acute exposure of Caco-2/15 cells to FE/ASC-catalyzed peroxidation produces harmful effects on mitochondrial functions and DNA integrity, which are abrogated by the powerful exogenous BHT antioxidant. Functional derangements of mitochondria may have implications in oxidative stress-related disorders such as inflammatory bowel diseases.

TRPC1 Deletion Causes Striatal Neuronal Cell Apoptosis and Proteomic Alterations in Mice.

PubMed

Wang, Dian; Yu, Haitao; Xu, Benhong; Xu, Hua; Zhang, Zaijun; Ren, Xiaohu; Yuan, Jianhui; Liu, Jianjun; Guo, Yi; Spencer, Peter S; Yang, Xifei

2018-01-01

Transient receptor potential channel 1 (TRPC1) is widely expressed throughout the nervous system, while its biological role remains unclear. In this study, we showed that TRPC1 deletion caused striatal neuronal loss and significantly increased TUNEL-positive and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining in the striatum. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) revealed a total of 51 differentially expressed proteins (26 increased and 25 decreased) in the stratum of TRPC1 knockout (TRPC1 -/- ) mice compared to that of wild type (WT) mice. Bioinformatics analysis showed these dysregulated proteins included: oxidative stress-related proteins, synaptic proteins, endoplasmic reticulum (ER) stress-related proteins and apoptosis-related proteins. STRING analysis showed these differential proteins have a well-established interaction network. Based on the proteomic data, we revealed by Western-blot analysis that TRPC1 deletion caused ER stress as evidenced by the dysregulation of GRP78 and PERK activation-related signaling pathway, and elevated oxidative stress as suggested by increased 8-OHdG staining, increased NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUV2) and decreased protein deglycase (DJ-1), two oxidative stress-related proteins. In addition, we also demonstrated that TRPC1 deletion led to significantly increased apoptosis in striatum with concurrent decrease in both 14-3-3Z and dynamin-1 (D2 dopamine (DA) receptor binding), two apoptosis-related proteins. Taken together, we concluded that TRPC1 deletion might cause striatal neuronal apoptosis by disturbing multiple biological processes (i.e., ER stress, oxidative stress and apoptosis-related signaling). These data suggest that TRPC1 may be a key player in the regulation of striatal cellular survival and death.

Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder.

PubMed

Sun, Xiao R; Zhang, Hui; Zhao, Hong T; Ji, Mu H; Li, Hui H; Wu, Jing; Li, Kuan Y; Yang, Jian J

2016-10-01

Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, which is characterized by anxiety- and depression-like behaviors and cognitive impairment. However, the underlying mechanisms remain elusive. Parvalbumin (PV) interneurons that are susceptible to oxidative stress are a subset of inhibitory GABAergic neurons regulating the excitability of pyramidal neurons, while dysfunction of PV interneurons is casually linked to many mental disorders including PTSD. We therefore hypothesized that environmental enrichment (EE), a method of enhanced cognitive, sensory and motor stimulation, can reverse the behavioral impairments by normalizing PV interneurons in a rat model of PTSD induced by inescapable foot shocks (IFS). Behavioral changes were determined by the open field, elevated plus maze, fear conditioning, and Morris water maze tests. The levels of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NOX4, PV, glutamic acid decarboxylase 67 (GAD-67), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in the hippocampus and prefrontal cortex were determined. Our results showed that in this PTSD model, rats displayed the anxiety-like behavior, enhanced fear learning behavior, and hippocampus- dependent spatial memory deficit, which were accompanied by the up-regulation of NOX2, 8-OH-dG, and down-regulation of PV and GAD-67. Notably, EE reversed all these abnormalities. These results suggest that restoration of PV interneurons by inhibiting oxidative stress in the hippocampus and prefrontal cortex might represent a mechanism through which EE reverses the behavioral impairments in a rat model of PTSD induced by IFS. Copyright © 2016 Elsevier B.V. All rights reserved.

Branched-Chain Amino Acid-Rich Supplements Containing Microelements Have Antioxidant Effects on Nonalcoholic Steatohepatitis in Mice.

PubMed

Tanaka, Hiroaki; Fukahori, Suguru; Baba, Shinji; Ueno, Takato; Sivakumar, Ramadoss; Yagi, Minoru; Asagiri, Kimio; Ishii, Shinji; Tanaka, Yoshiaki

2016-05-01

The aim of the present study was to elucidate whether the administration of antioxidant-rich nutrients, including branched-chain amino acids (BCAAs), microelements, and vitamins, both alone and in combination, has a positive impact on liver function in a nonalcoholic steatohepatitis (NASH) mouse model and identify the mechanisms underlying these effects. Seven-week-old male KKAy mice fed a methionine- and choline-deficient diet (MCD) for 4 weeks were divided into 7 groups and fed the following planned diets for another 4 weeks: group A (normal diet), group B (MCD; control), group C (MCD with rich microelements), group D (MCD with rich BCAAs), group E (MCD with rich microelements and BCAAs), and group F (MCD with rich microelements, BCAAs, and vitamins). We then conducted biochemical assays, histological analyses, immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2'-nonenal (4-HNE), and Western blotting for insulin glucose signaling, lipid metabolism, and endoplasmic reticulum (ER) stress-related signaling in liver specimens obtained from mice in each group. The morphometric grades of all NASH-related findings and the mean degree of 8-OHdG immunolocalization in groups D-F were significantly lower than those observed in group B. The expression levels of insulin receptor β subunit (IRβ) and p-elF in groups E and F and those of phosphatidyl-inositol 3 kinase (PI3K85), p-AcelCoA, and PERK in group F were similar to those noted in group A. The administration of a combination of antioxidant-rich nutrients, including BCAAs and microelements, is likely to suppress the progression of NASH by reducing oxidative stress, primarily via the downregulation of the ER stress pathway. © 2014 American Society for Parenteral and Enteral Nutrition.

Methane attenuates retinal ischemia/reperfusion injury via anti-oxidative and anti-apoptotic pathways.

PubMed

Liu, Lin; Sun, Qinglei; Wang, Ruobing; Chen, Zeli; Wu, Jiangchun; Xia, Fangzhou; Fan, Xian-Qun

2016-09-01

Retinal ischemia/reperfusion injury (IRI) may cause incurable visual impairment due to neural regeneration limits. Methane was shown to exert a protective effect against IRI in many organs. This study aims to explore the possible protective effects of methane-rich saline against retinal IRI in rat. Retinal IRI was performed on the right eyes of male Sprague-Dawley rats, which were immediately injected intraperitoneally with methane-saturated saline (25ml/kg). At one week after surgery, the number of retinal ganglion cells (RGCs), total retinal thickness, visual function were measured by hematoxylin and eosin staining, FluoroGold anterograde labeling and flash visual evoked potentials. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-Hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in retinas were assessed by immunofluorescence staining, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. As expected, methane treatment significantly improved the retinal IRI-induced RGC loss, total retinal layer thinning and visual dysfunction. Moreover, methane treatment significantly reduced the levels of oxidative stress biomarkers (8-OHdG, 4-HNE, MDA) and increased the antioxidant enzyme activities (SOD, CAT, GPx) in the retinas with IRI. Meanwhile, methane treatment significantly increased the anti-apoptotic gene (Bcl-2) expression and decreased the pro-apoptotic gene (Bax) expression, accompanied by the suppression of caspase-3 and caspase-9 activity. Thus, these data demonstrated that methane can exert a neuroprotective role against retinal IRI through anti-oxidative and anti-apoptotic pathways. Copyright © 2016. Published by Elsevier B.V.

Polysaccharides from Cordyceps sinensis mycelium ameliorate exhaustive swimming exercise-induced oxidative stress.

PubMed

Yan, Feng; Wang, Beibei; Zhang, Yan

2014-02-01

Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae) is a famous medicinal fungus (mushroom) in Chinese herbal medicine. Polysaccharides from Cordyceps sinensis (CSP) have been identified as active ingredients responsible for its biological activities. Although many pharmacological actions of CSP have received a great deal of attention, research in this area continues. The current study was designed to investigate the effects of CSP on exhaustive exercise-induced oxidative stress. The mice were divided into four groups: control (C), low-dose CSP treated (LC), intermediate-dose CSP treated (IC) and high-dose CSP treated (HC). The treated groups received CSP (100, 200 and 400 mg/kg, ig), while the control group received drinking water for 28 days, followed by being forced to undergo exhaustive swimming exercise, and some biochemical parameters including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured using detection kits according to the manufacturers' instructions. Compared with the C group, exhaustive swimming time was significantly prolonged in the LC, IC and HC groups (p < 0.05); SOD activities in serum, liver and muscle were significantly higher in the IC and HC groups (p < 0.05); GPx activities in serum, liver and muscle were significantly higher in the LC, IC and HC groups (p < 0.05); CAT activities in serum, liver and muscle were significantly higher in the HC groups (p < 0.05); MDA and 8-OHdG levels in serum, liver and muscle were significantly lower in the LC, IC and HC groups (p < 0.05). The results obtained herein indicate that CSP could ameliorate exhaustive exercise-induced oxidative stress.

Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage and nuclear factor-kappaB activation.

PubMed

Kubota, Shunsuke; Kurihara, Toshihide; Mochimaru, Hiroshi; Satofuka, Shingo; Noda, Kousuke; Ozawa, Yoko; Oike, Yuichi; Ishida, Susumu; Tsubota, Kazuo

2009-07-01

Resveratrol is known as one of the antioxidant polyphenols contained in red wine and grape skin. The purpose of the present study was to investigate the role of resveratrol in ocular inflammation in endotoxin-induced uveitis (EIU). EIU was induced in male C57/B6 mice at the age of 6 weeks by a single intraperitoneal injection of lipopolysaccharide (LPS). Animals had received oral supplementation of resveratrol at the doses of 5, 50, 100, or 200 mg/kg for 5 days until LPS injection. Twenty-four hours after LPS administration, leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. Retinal and retinal pigment epithelium (RPE)-choroidal levels of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear translocation of nuclear factor (NF)-kappaB p65 were evaluated by enzyme-linked immunosorbent assay. Retinal and RPE-choroidal activities of silent information regulator two ortholog (SIRT) 1 were measured by deacetylase fluorometric assay. Resveratrol pretreatment led to significant and dose-dependent suppression of leukocyte adhesion to retinal vessels of EIU mice compared with vehicle application. Protein levels of MCP-1 and ICAM-1 in the retina and the RPE-choroid of EIU animals were significantly reduced by resveratrol administration. Importantly, resveratrol-treated animals showed significant decline of retinal 8-OHdG generation and nuclear NF-kappaB P65 translocation, both of which were upregulated after EIU induction. RPE-choroidal SIRT1 activity, reduced in EIU animals, was significantly augmented by treatment with resveratrol. Resveratrol prevented EIU-associated cellular and molecular inflammatory responses by inhibiting oxidative damage and redox-sensitive NF-kappaB activation.

Advanced Collaborative Emissions Study Auxiliary Findings on 2007-Compliant Diesel Engines: A Comparison With Diesel Exhaust Genotoxicity Effects Prior to 2007

PubMed Central

Hallberg, Lance M; Ward, Jonathan B; Wickliffe, Jeffrey K; Ameredes, Bill T

2017-01-01

Since its beginning, more than 117 years ago, the compression-ignition engine, or diesel engine, has grown to become a critically important part of industry and transportation. Public concerns over the health effects from diesel emissions have driven the growth of regulatory development, implementation, and technological advances in emission controls. In 2001, the United States Environmental Protection Agency and California Air Resources Board issued new diesel fuel and emission standards for heavy-duty engines. To meet these stringent standards, manufacturers used new emission after-treatment technology, and modified fuel formulations, to bring about reductions in particulate matter and nitrogen oxides within the exhaust. To illustrate the impact of that technological transition, a brief overview of pre-2007 diesel engine exhaust biomarkers of genotoxicity and health-related concerns is provided, to set the context for the results of our research findings, as part of the Advanced Collaborative Emissions Study (ACES), in which the effects of a 2007-compliant diesel engine were examined. In agreement with ACES findings reported in other tissues, we observed a lack of measurable 2007-compliant diesel treatment–associated DNA damage, in lung tissue (comet assay), blood serum (8-hydroxy-2′-deoxyguanosine [8-OHdG] assay), and hippocampus (lipid peroxidation assay), across diesel exhaust exposure levels. A time-dependent assessment of 8-OHdG and lipid peroxidation also suggested no differences in responses across diesel exhaust exposure levels more than 24 months of exposure. These results indicated that the 2007-compliant diesel engine reduced measurable reactive oxygen species–associated tissue derangements and suggested that the 2007 standards–based mitigation approaches were effective. PMID:28659715

Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.

PubMed

Carvalho-Silva, Milena; Gomes, Lara M; Scaini, Giselli; Rebelo, Joyce; Damiani, Adriani P; Pereira, Maiara; Andrade, Vanessa M; Gava, Fernanda F; Valvassori, Samira S; Schuck, Patricia F; Ferreira, Gustavo C; Streck, Emilio L

2017-08-01

Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.

The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice.

PubMed

Kirkpatrick, Meg; Benoit, Janina; Everett, Wyll; Gibson, Jennifer; Rist, Michael; Fredette, Nicholas

2015-09-01

Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3. Copyright © 2015 Elsevier Inc. All rights reserved.

Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

PubMed Central

2017-01-01

Purpose We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. Materials and Methods Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. Results Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. Conclusions Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model. PMID:29076302

Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

PubMed

Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

2008-07-01

Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia. 2008 Wiley-Liss, Inc.

THE EFFECT OF GREEN TEA ON OXIDATIVE DAMAGE AND TUMOUR FORMATION IN LOBUND-WISTAR RATS

PubMed Central

O'Sullivan, Jacintha; Sheridan, Juliette; Mulcahy, Hugh; Tenniswood, Martin; Morrissey, Colm

2014-01-01

A number of epidemiological studies suggest that the consumption of green tea reduces the incidence of prostate cancer. Since the major catechins present in green tea are potent anti-oxidants, we hypothesized that genetic and cellular damage induced by oxygen free radicals could be significantly reduced by potent anti-oxidants in green tea, thus reducing the cumulative genetic and cellular damage with age, and slowing or preventing tumour formation. Long-term administration of a decaffeinated green tea extract to Lobund-Wistar rats for periods up to 26 months almost halved the incidence of primary tumours in the genitourinary tract when compared to an aged-matched cohort receiving just water. We observed no inhibition of DNA adduct formation or lipid peroxidation in animals consuming green tea compared to animals consuming de-ionized water. The decrease in tumour formation was associated with an increase in 8-hydroxy-2’deoxyguanosine (8-OH-dG) and 4-hydroxynonenal (4-HNE) content (markers of DNA adduct formation and lipid peroxidation respectively) in the epithelium of the ventral prostate in aging animals. There was also an increase in 8-OH-dG expression, but no change in 4-HNE expression in the seminal vesicles of older animals. There was an age associated increase in expression of the anti-oxidant enzymes MnSOD and catalase in the epithelium of the ventral prostate of aging animals. There was also an increase in MnSOD expression, but no change in catalase expression in the seminal vesicles of older animals. These data demonstrate that consumption of green tea decreases the incidence of genitourinary tract tumours in the Lobund-Wistar rat, but has no effect on age associated DNA adduct formation and lipid peroxidation in the aging rat ventral prostate and seminal vesicles. PMID:18941371

Occupational cosmic radiation exposure in Portuguese airline pilots: study of a possible correlation with oxidative biological markers.

PubMed

Silva, Rodrigo; Folgosa, Filipe; Soares, Paulo; Pereira, Alice S; Garcia, Raquel; Gestal-Otero, Juan Jesus; Tavares, Pedro; Gomes da Silva, Marco D R

2013-05-01

Several studies have sought to understand the health effects of occupational exposure to cosmic radiation. However, only few biologic markers or associations with disease outcomes have so far been identified. In the present study, 22 long- and 26 medium-haul male Portuguese airline pilots and 36 factory workers who did not fly regularly were investigated. The two groups were comparable in age and diet, were non-smokers, never treated with ionizing radiation and other factors. Cosmic radiation exposure in pilots was quantified based on direct monitoring of 51 flights within Europe, and from Europe to North and South America, and to Africa. Indirect dose estimates in pilots were performed based on the SIEVERT (Système informatisé d'évaluation par vol de l'exposition au rayonnement cosmique dans les transports aériens) software for 6,039 medium- and 1,366 long-haul flights. Medium-haul pilots had a higher cosmic radiation dose rate than long-haul pilots, that is, 3.3 ± 0.2 μSv/h and 2.7 ± 0.3 μSv/h, respectively. Biological tests for oxidative stress on blood and urine, as appropriate, at two time periods separated by 1 year, included measurements of antioxidant capacity, total protein, ferritin, hemoglobin, creatinine and 8-hydroxy-2-deoxyguanosine (8OHdG). Principal components analysis was used to discriminate between the exposed and unexposed groups based on all the biological tests. According to this analysis, creatinine and 8OHdG levels were different for the pilots and the unexposed group, but no distinctions could be made among the medium- and the long-haul pilots. While hemoglobin levels seem to be comparable between the studied groups, they were directly correlated with ferritin values, which were lower for the airline pilots.

[Iodine nutritional status of the vulnerable population in Henan province in 2011].

PubMed

Yang, Jin; Zheng, He-ming; Chen, Gan

2013-01-01

To investigate the iodine nutritional status of the vulnerable population in Henan in 2011. From March to December 2011, 44 049 urinary samples of newly married women of childbearing age (363), pregnant women (31 874), lactating women (4893) and children under 2 years (6919) collected from hospitals, maternal and child care hospitals and outpatient department of family planning organizations from 8 cities of Henan province (only including the areas where water iodine was less than 100 µg/L) were tested for urine iodine concentration. The iodine nutritional status of different groups was analyzed. The median of urinary iodine for newly married women, pregnant women, lactating women and children under 2 years was 204.5, 190.9, 145.5 and 185.4 µg/L, respectively (χ(2) = 874.16, P < 0.01). The proportion of urinary iodine below 150 µg/L of pregnant women and below 100 µg/L of lactating women and children under 2 years was 33.0% (10 519/31 874), 24.9% (1218/4893) and 12.4% (855/6919), respectively. The proportion of urinary iodine above 300 µg/L of newly married women was 33.6% (122/363). The median of urinary iodine for pregnant women in the first, second and third trimester was 186.7, 193.8 and 182.5 µg/L, respectively (χ(2) = 55.19, P < 0.01). The median of urinary iodine for the breast-feeding, formula-feeding and mixed-feeding infant under the age of 1 year was 194.8, 85.6 and 176.0 µg/L, respectively (χ(2) = 179.25, P < 0.01). The overall iodine nutrient levels of the vulnerable population in Henan in 2011 were appropriate, but there were still some proportions of pregnant and lactating women with low iodine level. The iodine intake of the formula-feeding infants was not sufficient.

Urinary free light chains may help to identify infection in patients with elevated systemic inflammation due to rheumatic disease.

PubMed

Bramlage, Carsten P; Froelich, Britta; Wallbach, Manuel; Minguet, Joan; Grupp, Clemens; Deutsch, Cornelia; Bramlage, Peter; Müller, Gerhard A; Koziolek, Michael

2017-04-01

The risk of infection in patients with rheumatic diseases is elevated, but a clear marker to differentiate the cause of the systemic inflammation is missing. We assessed the ability urinary immunoglobulin free light chains (FLCs) to indicate the presence of infection in patients with rheumatic disease. We performed a retrospective analysis of patients with rheumatic disease attending the Georg-August University Hospital in Goettingen, Germany, from January 2011 to December 2013. Subjects were included if they had urine levels of κ and λ FLCs available. A reference group of patients without autoimmune disease, but with documented infection, was constructed. A total of 1500 patients had their urinary FLCs quantified during the study period. Of the 382 patients with rheumatic disease, 172 (45%) displayed no systemic inflammation, 162 (42%) had inflammation due to the underlying disease activity, and 48 (13%) had inflammation due to a confirmed infection. Urinary FLC concentrations were much higher in patients with rheumatic diseases and infection (κ 68.8 ± 81.8 mg/L, λ 31.4 ± 53.5 mg/L) compared to those with inflammation due to rheumatic disease activity (κ 22.7 ± 26.3 mg/L, λ 8.1 ± 9.1 mg/L, κ p < 0.001, λ p = 0.004). Urinary κ FLCs demonstrated good ability to predict infection, with a sensitivity of 63% and specificity of 84%. Urinary λ FLCs gave similar values, with a sensitivity of 65% and specificity of 81%. FLCs may be useful for distinguishing inflammation due to rheumatic disease activity from that due to the additional presence of infection. The ability to quantify these proteins in urine provides a simple alternative to the use of blood.

Urinary bisphenol A levels in Turkish girls with premature thelarche.

PubMed

Durmaz, E; Asci, A; Erkekoglu, P; Balcı, A; Bircan, I; Koçer-Gumusel, B

2018-01-01

There is a growing concern over the timing of pubertal breast development and its possible association with exposure to endocrine disrupting chemicals (EDCs), such as bisphenol A (BPA). BPA is abundantly used to harden plastics. The aim of this study was to investigate the relation between premature thelarche (PT) and BPA by comparing the urinary BPA levels of PT girls with those of healthy subjects. Twenty-five newly diagnosed nonobese PT subjects (aged 4-8 years) who were admitted to the Pediatric Endocrinology Department at Akdeniz University were recruited. The control group composed of 25 age-matched girls without PT and other endocrine disorders. Urinary BPA levels were measured by high pressure liquid chromatography. The median urinary concentrations of BPA were found to be significantly higher in the PT group compared to the healthy control group (3.2 vs. 1.62 μg/g creatinine, p < 0.05). We observed a weak positive correlation between uterus volume and urinary BPA levels. There was a weak correlation between estradiol and urinary BPA levels ( r = 0.166; p = 0.37); and luteinizing hormone and urinary BPA levels ( r = 0.291; p = 0.08) of PT girls. Our results suggest that exposure to BPA might be one of the underlying factors of early breast development in prepubertal girls and EDCs may be considered as one of the etiological factors in the development of PT.

Renal excretion of intravenously infused amoxycillin and ampicillin.

PubMed Central

Sjövall, J; Westerlund, D; Alván, G

1985-01-01

The aim of this study was to determine whether concentration-dependent renal clearance of ampicillin and amoxycillin occurs. The drugs were given as single 20 min i.v. infusions in doses ranging from 1.9 to 2.8 g to nine healthy volunteers using a cross-over design. Plasma and urinary concentrations were determined by a selective liquid chromatographic method using frequent sampling up to 10 and 30 h respectively after termination of the infusion. The renal clearance of the drugs was independent of the plasma concentration. The mean (s.d.) renal clearances of ampicillin and amoxycillin were 167 (24) and 157 (20) ml min-1 1.73 m-2 respectively. The net secretion was about 50% of the total renal clearance of both drugs. The plasma concentration and urinary excretion rate versus time curves indicated a polyexponential decline, which could be described by both a biexponential and a triexponential equation. The former proved to be more reliable, especially in the calculation of micro rate constants. There was a tendency to more sustained plasma concentrations after amoxycillin, also illustrated by a significantly lower mean (s.d.) plasma clearance of this drug, viz. 185 (30) ml min-1 1.73 m-2, as compared to ampicillin, 210 (24) ml min-1 1.73 m-2 (P less than 0.04). There were no major differences in the disposition rate constants and the distribution volumes of ampicillin and amoxycillin. The mean (s.d.) plasma half-life was 1.7 (0.3) h for both drugs. The urinary excretion rate indicated a slower terminal disposition rate however, with ampicillin and amoxycillin half-lives of 3.4 (2.0) and 3.9 (1.2) h respectively. The longer half-life in the terminal phase may be due to increased tubular reabsorption at low urinary concentrations. It was not possible to determine in this study whether the half-life was affected by changes in clearance or volume of distribution. The urinary solubility of the drugs was dependent on pH. This could explain the massive macroscopic crystalluria seen in one subject after amoxycillin. Three hours after termination of the infusion, crystals could no longer be found in the sediment. There was no clinical or laboratory evidence of renal damage. PMID:3986077

Diets naturally rich in polyphenols improve fasting and postprandial dyslipidemia and reduce oxidative stress: a randomized controlled trial.

PubMed

Annuzzi, Giovanni; Bozzetto, Lutgarda; Costabile, Giuseppina; Giacco, Rosalba; Mangione, Anna; Anniballi, Gaia; Vitale, Marilena; Vetrani, Claudia; Cipriano, Paola; Della Corte, Giuseppina; Pasanisi, Fabrizio; Riccardi, Gabriele; Rivellese, Angela A

2014-03-01

The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk. This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress. According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured. Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane. Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk.

Urinary and faecal N-methylhistamine concentrations do not serve as markers for mast cell activation or clinical disease activity in dogs with chronic enteropathies.

PubMed

Anfinsen, Kristin P; Berghoff, Nora; Priestnall, Simon L; Suchodolski, Jan S; Steiner, Jörg M; Allenspach, Karin

2014-12-21

This study sought to correlate faecal and urinary N-methylhistamine (NMH) concentrations with resting versus degranulated duodenal mast cell numbers in dogs with chronic enteropathies (CE), and investigate correlations between intestinal mast cell activation and clinical severity of disease as assessed by canine chronic enteropathy clinical activity index (CCECAI), and between urinary and faecal NMH concentrations, mast cell numbers, and histopathological scores. Twenty-eight dogs with CE were included. Duodenal biopsies were stained with haematoxylin and eosin (H&E), toluidine blue, and by immunohistochemical labelling for tryptase. Duodenal biopsies were assigned a histopathological severity score, and duodenal mast cell numbers were counted in five high-power fields after metachromatic and immunohistochemical staining. Faecal and urinary NMH concentrations were measured by gas chromatography-mass spectrometry. There was no correlation between the CCECAI and faecal or urinary NMH concentrations, mast cell numbers, or histopathological score - or between faecal or urinary NMH concentration and mast cell numbers. Post hoc analysis revealed a statistically significant difference in toluidine blue positive mast cells between two treatment groups (exclusion diet with/without metronidazole versus immunosuppression (IS)), with higher numbers among dogs not requiring IS. Faecal and urinary NMH concentrations and duodenal mast cell numbers were not useful indicators of severity of disease as assessed by the CCECAI or histological evaluation. The number of duodenal mast cells was higher in dogs that did not need IS, i.e. in dogs responding to an exclusion diet (with/without metronidazole), than in dogs requiring IS. Further studies comparing the role of mast cells in dogs with different forms of CE are needed.

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horton, Megan K., E-mail: megan.horton@mssm.edu; Blount, Benjamin C.; Valentin-Blasini, Liza

Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New Yorkmore » City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood. • Weighted quantile sum (WQS) regression examined complex mixture effect. • WQS identified an inverse association between the exposure mixture and maternal TSH. • Perchlorate indicated as the ‘bad actor’ of the mixture.« less

Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study.

PubMed

Hsu, Ling-I; Hsieh, Fang-I; Wang, Yuan-Hung; Lai, Tai-Shuan; Wu, Meei-Maan; Chen, Chien-Jen; Chiou, Hung-Yi; Hsu, Kuang-Hung

2017-12-01

Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified. The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study. 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7μg/L at the 50th, 75th, and 90th percentiles, respectively. Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration. Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan's National Health Insurance database 1998 to 2011. HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion ≥ 200mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression. We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 10 4 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration ≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and ≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th percentiles of total urinary arsenic concentrations were associated with 50% and 67% higher prevalences, respectively, of proteinuria. Kidney diseases and CKD outcomes were based on diagnostic codes. Glomerular filtration rates were not available. Other heavy metals were not measured. This study describes the temporal relationship between arsenic concentrations ≥ 10μg/L in drinking water and CKD. A dose-dependent association between well-water arsenic concentration and kidney diseases was observed. Higher creatinine-adjusted urinary total arsenic concentrations were associated with a higher prevalence of proteinuria. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Vinyl flooring in the home is associated with children’s airborne butylbenzyl phthalate and urinary metabolite concentrations

PubMed Central

Just, Allan C.; Miller, Rachel L.; Perzanowski, Matthew S.; Rundle, Andrew G.; Chen, Qixuan; Jung, Kyung Hwa; Hoepner, Lori; Camann, David E.; Calafat, Antonia M.; Perera, Frederica P.; Whyatt, Robin M.

2015-01-01

Prior studies have shown that vinyl flooring, as well as the vinyl-softening plasticizers butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP), are associated with asthma and airway inflammation. While DEHP exposure is primarily dietary, whether home vinyl flooring contributes to indoor air and urinary metabolite concentrations for these two phthalates is unclear. Exposures to BBzP and DEHP were examined in a prospective birth cohort of New York City children (n=239) using: (1) visual observation of potential phthalate containing flooring, (2) a two-week home indoor air sample, and (3) concurrent urinary metabolites in a subset (n=193). The category “vinyl or linoleum” flooring was observed in 135 (56%) of monitored rooms; these rooms had statistically significantly higher indoor air geometric mean concentrations of BBzP (23.9 ng/m3) than rooms with wood or carpet flooring (10.6 ng/m3). Children from homes with “vinyl or linoleum” flooring also had significantly higher urinary BBzP metabolite concentrations than other children. Indoor air BBzP and urinary metabolite concentrations were correlated positively (Spearman’s rho 0.40). By contrast, indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations. Vinyl flooring in the home may be an important source of children’s exposure to BBzP via indoor air. PMID:25690585

Vinyl flooring in the home is associated with children's airborne butylbenzyl phthalate and urinary metabolite concentrations.

PubMed

Just, Allan C; Miller, Rachel L; Perzanowski, Matthew S; Rundle, Andrew G; Chen, Qixuan; Jung, Kyung Hwa; Hoepner, Lori; Camann, David E; Calafat, Antonia M; Perera, Frederica P; Whyatt, Robin M

2015-01-01

Prior studies have shown that vinyl flooring as well as the vinyl-softening plasticizers butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) are associated with asthma and airway inflammation. Although DEHP exposure is primarily dietary, whether home vinyl flooring contributes to indoor air and urinary metabolite concentrations for these two phthalates is unclear. Exposures to BBzP and DEHP were examined in a prospective birth cohort of New York City children (n=239) using: (i) visual observation of potential phthalate containing flooring, (ii) a 2-week home indoor air sample, and (iii) concurrent urinary metabolites in a subset (n=193). The category "vinyl or linoleum" flooring was observed in 135 (56%) of monitored rooms; these rooms had statistically significantly higher indoor air geometric mean concentrations of BBzP (23.9 ng/m(3)) than rooms with wood or carpet flooring (10.6 ng/m(3)). Children from homes with "vinyl or linoleum" flooring also had significantly higher urinary BBzP metabolite concentrations than other children. Indoor air BBzP and urinary metabolite concentrations were correlated positively (Spearman's rho 0.40). By contrast, indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations. Vinyl flooring in the home may be an important source of children's exposure to BBzP via indoor air.

Assessment of 1H NMR-based metabolomics analysis for normalization of urinary metals against creatinine.

PubMed

Cassiède, Marc; Nair, Sindhu; Dueck, Meghan; Mino, James; McKay, Ryan; Mercier, Pascal; Quémerais, Bernadette; Lacy, Paige

2017-01-01

Proton nuclear magnetic resonance ( 1 H NMR, or NMR) spectroscopy and inductively coupled plasma-mass spectrometry (ICP-MS) are commonly used for metabolomics and metal analysis in urine samples. However, creatinine quantification by NMR for the purpose of normalization of urinary metals has not been validated. We assessed the validity of using NMR analysis for creatinine quantification in human urine samples in order to allow normalization of urinary metal concentrations. NMR and ICP-MS techniques were used to measure metabolite and metal concentrations in urine samples from 10 healthy subjects. For metabolite analysis, two magnetic field strengths (600 and 700MHz) were utilized. In addition, creatinine concentrations were determined by using the Jaffe method. Creatinine levels were strongly correlated (R 2 =0.99) between NMR and Jaffe methods. The NMR spectra were deconvoluted with a target database containing 151 metabolites that are present in urine. A total of 50 metabolites showed good correlation (R 2 =0.7-1.0) at 600 and 700MHz. Metal concentrations determined after NMR-measured creatinine normalization were comparable to previous reports. NMR analysis provided robust urinary creatinine quantification, and was sufficient for normalization of urinary metal concentrations. We found that NMR-measured creatinine-normalized urinary metal concentrations in our control subjects were similar to general population levels in Canada and the United Kingdom. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Urine Matrix and pH on the Potency of Delafloxacin and Ciprofloxacin against Urogenic Escherichia coli and Klebsiella pneumoniae.

PubMed

So, Wonhee; Crandon, Jared L; Nicolau, David P

2015-08-01

We assessed the effects of the urine matrix and its varying pH on the potency of the novel broad-spectrum fluoroquinolone delafloxacin and of ciprofloxacin against 16 urogenic Enterobacteriaceae in the urine of patients with suspected urinary tract infection. We determined minimum inhibitory concentrations in broth and urine using microdilution in 9 Escherichia coli and 7 Klebsiella pneumoniae specimens. The change in potency between broth and urine was calculated. Against 16 highly ciprofloxacin resistant Enterobacteriaceae with a broth minimum inhibitory concentration of 32 mg/l or greater the minimum inhibitory concentration in delafloxacin in broth was 2 mg/l (1 and 0 isolates of E. coli and K. pneumoniae, respectively), 4 mg/l (3 and 0), 8 mg/l (3 and 1), 16 mg/l (2 and 4) and 32 mg/l (0 and 2). Across the 143 collected urines pH ranged from 4.7 to 9.0 with 71% at pH 6.5 or less. The delafloxacin minimum inhibitory concentration measured in 80% urine from 100 unique patient samples (pH 5.0 to 8.3) was 2 mg/l or less (18% and 0.8% for E. coli and K. pneumoniae, respectively), 4 mg/l (23% and 6%), 8 mg/l (21% and 18%), 16 mg/l (23% and 33%) and 32 mg/l or greater (15% and 42%). For E. coli and K. pneumoniae combined the median changes in the delafloxacin minimum inhibitory concentration were a 1 doubling dilution decrease at pH 6.0 or less, no change at pH 6.1 to 7.0 and a 1 doubling dilution increase at pH 7.1 or greater. Unlike delafloxacin, ciprofloxacin showed a 1 doubling dilution increase for E. coli and no change for K. pneumoniae at pH 7.0 or less with no change observed at pH 7.1 or greater. Most urines collected from patients with urinary tract infection had a pH of 6.5 or less. Delafloxacin broth minimum inhibitory concentrations were twofold to fivefold doubling dilutions lower than those of ciprofloxacin. In contrast to ciprofloxacin, the potency of delafloxacin was further enhanced in the acidic environment commonly observed in the setting of urinary tract infection. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Nitrite/Nitrate responses to endotoxin in calves.

PubMed

Hüsler, B R; Blum, J W

2001-10-01

Plasma concentrations and urinary excretions of nitrite plus nitrate (NOx) increase in heifers after endotoxin-induced nitric oxide synthase activation. The rise can be enhanced by administration of arginine, the substrate for the production of nitric oxide, whose effects may be modified by the iron status. In 10-week-old veal calves (six Simmental x Red Holstein) arginine (0.5 g/kg body weight for 6 h) was intravenously infused. At 2 h after the start of the infusions Escherichia coli endotoxin O26:B6 (2 microg/kg body weight) was intravenously injected. This caused a rise of rectal temperature, heart rate, respiration rate, and of urinary NOx excretion, but not of plasma NOx concentrations, in contrast to the experience with older cattle to which the same amounts of arginine were infused before and during endotoxin administration. In 8-week-old veal calves (18 Simmental x Red Holstein) the question of whether oral supplementation with arginine and iron modifies NOx responses to endotoxin (2 microg/kg) was also investigated. The calves were divided between three groups (GrA-, GirA+, GrC) and before endotoxin injections GrA- was fed 0.5 g arginine/kg for 4 days, GrA+ was fed 0.5 g arginine/kg for 4 days plus 80 mg iron/kg milk for 2 weeks, whereas GrC was not supplemented with arginine or iron. Iron supplementation increased plasma iron concentrations and arginine supplementation increased plasma arginine and urea concentrations and urinary urea excretion. Ensuing administration of endotoxin enhanced plasma tumour necrosis factor-alpha concentrations, rectal temperature, heart rate, and respiration rate, but not plasma NOx concentrations in GrC and GrA- and only transiently and slightly increased plasma NOx concentrations in GrA+ but did not affect urinary NOx excretions. In conclusion, the expected stimulation of NOx responses to endotoxin by intravenous arginine infusion appears to be much weaker in young veal calves than in older cattle. The NOx responses in young veal calves were not modified if arginine was orally administered and plasma NOx were barely enhanced by combined oral supplementation of arginine and iron.

Sodium interference in the determination of urinary aldosterone.

PubMed

Aldea, Marta Lucía; Barallat, Jaume; Martín, María Amparo; Rosas, Irene; Pastor, María Cruz; Granada, María Luisa

2016-02-01

Primary hyperaldosteronism (PHA) is one of the most common endocrine forms of secondary hypertension. Among the most used confirmatory tests for PHA is urinary aldosterone determination after oral sodium loading test. The primary aim of our study was to investigate if sodium concentrations interfere with urinary aldosterone in an automated competitive immunoassay (Liaison®) as well as to verify the manufacturer's specifications. 24-hr urine samples were collected and stored frozen until assayed. Two pools at low and high aldosterone concentrations were prepared. Verification of performance for precision was tested according to Clinical and Laboratory Standards Institute (CLSI) document EP15-A2 and interference with increasing concentrations of NaCl according to CLSI EP7-A2. The assay met the quality specifications according to optimal biological variation. Our results show that sodium concentrations up to 200mmol/L do not interfere on urinary aldosterone quantification, but sodium concentrations above 486mmol/L negatively interfere with the test. The Liaison® automated method is useful for aldosterone determination in the PHA confirmatory test, but interferences with NaCl may occur. It is therefore recommended to determine urinary NaCl before measuring urinary aldosterone to avoid falsely low results. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Comparison of questionnaire-based estimation of pesticide residue intake from fruits and vegetables with urinary concentrations of pesticide biomarkers.

PubMed

Chiu, Yu-Han; Williams, Paige L; Mínguez-Alarcón, Lidia; Gillman, Matthew; Sun, Qi; Ospina, Maria; Calafat, Antonia M; Hauser, Russ; Chavarro, Jorge E

2018-01-01

We developed a pesticide residue burden score (PRBS) based on a food frequency questionnaire and surveillance data on food pesticide residues to characterize dietary exposure over the past year. In the present study, we evaluated the association of the PRBS with urinary concentrations of pesticide biomarkers. Fruit and vegetable (FV) intake was classified as having high (PRBS≥4) or low (PRBS<4) pesticide residues for 90 men from the EARTH study. Two urine samples per man were analyzed for seven biomarkers of organophosphate and pyrethroid insecticides, and the herbicide 2,4-dichlorophenoxyacetic acid. We used generalized estimating equations to analyze the association of the PRBS with urinary concentrations of pesticide biomarkers. Urinary concentrations of pesticide biomarkers were positively related to high pesticide FV intake but inversely related to low pesticide FV intake. The molar sum of urinary concentrations of pesticide biomarkers was 21% (95% confidence interval (CI): 2%, 44%) higher for each one serving/day increase in high pesticide FV intake, and 10% (95% CI: 1%, 18%) lower for each one serving/day increase in low pesticide FV intake. Furthermore, intake of high pesticide FVs positively related to most individual urinary biomarkers. Our findings support the usefulness of the PRBS approach to characterize dietary exposure to select pesticides.

Elevated urinary levels of 8-oxo-2'-deoxyguanosine, (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines, and 8-iso-prostaglandin F2α as potential biomarkers of oxidative stress in patients with prediabetes.

PubMed

Kant, Melis; Akış, Merve; Çalan, Mehmet; Arkan, Tuğba; Bayraktar, Fırat; Dizdaroglu, Miral; İşlekel, Hüray

2016-12-01

Prediabetes is the preclinical stage of type 2 diabetes mellitus (T2DM) with intermediate state of hyperglycemia. Hyperglycemia results in a state of oxidative stress, which may contribute to the production of insulin resistance, β-cell dysfunction and long-term complications of diabetes. Novel approaches are required for prevention and treatment of diabetes. New biomarkers that can be used in risk stratification and therapy control as supplementary to current parameters are needed. These biomarkers may facilitate a more individualized and sufficient treatment of diabetes. Therefore, the aim of this study was to investigate the levels of oxidatively induced DNA damage products, 8-oxo-2'-deoxyguanosine (8-oxo-dG) (also known as 8-OH-dG), (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA), and the lipid peroxidation product 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) as reliable oxidative stress markers in patients with prediabetes or T2DM in comparison with healthy volunteers. Urine samples were collected from these subjects. Absolute quantification of 8-oxo-dG, R-cdA, S-cdA and 8-iso-PGF 2α was achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF 2α were significantly greater in prediabetes patients than those in healthy volunteers. T2DM patients also had higher levels of 8-oxo-dG than healthy volunteers. No statistically significant difference was observed for R-cdA levels. 8-Oxo-dG levels positively correlated with R-cdA and S-cdA levels for prediabetes and newly diagnosed T2DM. S-cdA levels and HbA1c were found negatively correlated in prediabetes patients. Also 8-iso-PGF 2α levels and HbA1c were found negatively correlated in prediabetes patients. These results indicate that oxidatively induced macromolecular damage appears before the establishment of T2DM. Thus, our data suggest that oxidatively induced DNA damage and lipid peroxidation products that were found to be elevated in prediabetic stage may be used as early disease markers in patients at risk for T2DM. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of transdermal magnesium cream on serum and urinary magnesium levels in humans: A pilot study.

PubMed

Kass, Lindsy; Rosanoff, Andrea; Tanner, Amy; Sullivan, Keith; McAuley, William; Plesset, Michael

2017-01-01

Oral magnesium supplementation is commonly used to support a low magnesium diet. This investigation set out to determine whether magnesium in a cream could be absorbed transdermally in humans to improve magnesium status. In this single blind, parallel designed pilot study, n = 25 participants (aged 34.3+/-14.8y, height 171.5+/-11cm, weight 75.9 +/-14 Kg) were randomly assigned to either a 56mg/day magnesium cream or placebo cream group for two weeks. Magnesium serum and 24hour urinary excretion were measured at baseline and at 14 days intervention. Food diaries were recorded for 8 days during this period. Mg test and placebo groups' serum and urinary Mg did not differ at baseline. After the Mg2+ cream intervention there was a clinically relevant increase in serum magnesium (0.82 to 0.89 mmol/l,p = 0.29) that was not seen in the placebo group (0.77 to 0.79 mmol/L), but was only statistically significant (p = 0.02)) in a subgroup of non-athletes. Magnesium urinary excretion increased from baseline slightly in the Mg2+ group but with no statistical significance (p = 0.48). The Mg2+ group showed an 8.54% increase in serum Mg2+ and a 9.1% increase in urinary Mg2+ while these figures for the placebo group were smaller, i.e. +2.6% for serum Mg2+ and -32% for urinary Mg2+. In the placebo group, both serum and urine concentrations showed no statistically significant change after the application of the placebo cream. No previous studies have looked at transdermal absorbency of Mg2+ in human subjects. In this pilot study, transdermal delivery of 56 mg Mg/day (a low dose compared with commercial transdermal Mg2+ products available) showed a larger percentage rise in both serum and urinary markers from pre to post intervention compared with subjects using the placebo cream, but statistical significance was achieved only for serum Mg2+ in a subgroup of non-athletes. Future studies should look at higher dosage of magnesium cream for longer durations. ISRCTN registry ID No. ISRTN15136969.

The effect of endurance exercise on both skeletal muscle and systemic oxidative stress in previously sedentary obese men

PubMed Central

Samjoo, I A; Safdar, A; Hamadeh, M J; Raha, S; Tarnopolsky, M A

2013-01-01

Background: Obesity is associated with low-grade systemic inflammation, in part because of secretion of proinflammatory cytokines, resulting into peripheral insulin resistance (IR). Increased oxidative stress is proposed to link adiposity and chronic inflammation. The effects of endurance exercise in modulating these outcomes in insulin-resistant obese adults remain unclear. We investigated the effect of endurance exercise on markers of oxidative damage (4-hydroxy-2-nonenal (4-HNE), protein carbonyls (PCs)) and antioxidant enzymes (superoxide dismutase (SOD), catalase) in skeletal muscle; urinary markers of oxidative stress (8-hydroxy-2-deoxyguanosine (8-OHdG), 8-isoprostane); and plasma cytokines (C-reactive protein (CRP), interleukin-6 (IL-6), leptin, adiponectin). Methods: Age- and fitness-matched sedentary obese and lean men (n=9 per group) underwent 3 months of moderate-intensity endurance cycling training with a vastus lateralis biopsy, 24-h urine sample and venous blood samples taken before and after the intervention. Results: Obese subjects had increased levels of oxidative damage: 4-HNE (+37% P⩽0.03) and PC (+63% P⩽0.02); evidence of increased adaptive response to oxidative stress because of elevated levels of copper/zinc SOD (Cu/ZnSOD) protein content (+84% P⩽0.01); increased markers of inflammation: CRP (+737% P⩽0.0001) and IL-6 (+85% P⩽0.03), and these correlated with increased markers of obesity; and increased leptin (+262% P⩽0.0001) with lower adiponectin (−27% P⩽0.01) levels vs lean controls. Training reduced 4-HNE (−10% P⩽0.04), PC (−21% P⩽0.05), 8-isoprostane (−26% P⩽0.02) and leptin levels (−33% P⩽0.01); had a tendency to decrease IL-6 levels (−21% P=0.07) and IR (−17% P=0.10); and increased manganese SOD (MnSOD) levels (+47% P⩽0.01). Conclusion: Endurance exercise reduced skeletal muscle-specific and systemic oxidative damage while improving IR and cytokine profile associated with obesity, independent of weight loss. Hence, exercise is a useful therapeutic modality to reduce risk factors associated with the pathogenesis of IR in obesity. PMID:24042701

Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and {beta} {sub 2}-microglobulinuria under environmental exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gamo, Masashi; Ono, Kyoko; Nakanishi, Junko

2006-05-15

A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and {beta} {sub 2}-microglobulinuria ({beta}2MG-uria) under environmental exposure. {beta}2MG-uria was defined by a cutoff point of 1000 {mu}g {beta} {sub 2}-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of {beta}2MG-uria reported in the literature andmore » those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of {beta}2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of {beta}2MG-uria. This was estimated to be approximately 3 {mu}g/g creatinine for a population in a small geographical area and approximately 2 {mu}g/g creatinine for a nationwide population.« less

A concurrent exposure to arsenic and fluoride from drinking water in Chihuahua, Mexico.

PubMed

González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Sánchez-Ramírez, Blanca; Ishida, María C; Barrera-Hernández, Angel; Gutiérrez-Torres, Daniela; Zacarias, Olga L; Saunders, R Jesse; Drobná, Zuzana; Mendez, Michelle A; García-Vargas, Gonzalo; Loomis, Dana; Stýblo, Miroslav; Del Razo, Luz M

2015-04-24

Inorganic arsenic (iAs) and fluoride (F-) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F- in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F- concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F-/L. Urinary arsenic (U-tAs) and urinary F- (U-F-) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F-/mL. A strong positive correlation was found between iAs and F- concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F- concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F-, raising questions about possible contribution of F- exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F- exposures and its related health risks deserves immediate attention.

[Pharmacokinetic and clinical studies of cefmenoxime in neonates and premature infants].

PubMed

Toyonaga, Y; Sugita, M; Kurosu, Y; Hori, M; Seo, K

1989-12-01

Serum concentrations and urinary recovery rates of cefmenoxime (CMX) were determined in 41 mature and premature infants (with ages 0-24 days) after one shot intravenous injection of 10, 20 (1-hour intravenous drip infusion was also carried out) or 30 mg/kg for treatment and prophylaxis of various infections. Because the number of cases included was small, a comparison study was conducted by classifying them into 3 groups; 3 days or younger, 4 to 7 days, and 8 days or older, rather than dividing them into groups of mature and premature infants. Clinical evaluation was conducted in 7 male and 1 female cases 1 to 29 days old, whose diseases comprised 1 case each with septicemia, purulent otitis media and phlegmonous cellulitis, 3 with pneumonia and 2 with urinary tract infection. 1. Changes in serum concentrations and urinary recovery rates (1) Intravenous bolus injection of 10 mg/kg: Serum concentrations of the drug in the 3 age groups peaked at 28.9, 29.5 and 29.1 micrograms/ml, respectively, all at 30 minutes after the drug administration, and thereafter gradually declined. The mean level in the 3rd group was the lowest at 1.9 micrograms/ml at 6 hours. Average serum half-lives of CMX were shorter in older subjects, 3.0, 1.9 and 1.4 hours, respectively in the 3 groups. Urinary recovery rates were relatively high, 68.9 to 84.9% in the 3 cases examined during the first 6 hours, and 15.4 to 66.2% during the first 2 hours. (2) Intravenous bolus injection of 20 mg/kg: Serum concentrations of the drug in the 3 groups peaked at 65.2, 60.5 and 65.8 micrograms/ml, respectively, all at 30 minutes after the drug administration, with no significant differences noted among the groups. The levels gradually declined thereafter in all groups, but remained rather high at 20.1, 6.5 and 9.5 micrograms/ml, respectively, at 6 hours. Average serum half-lives of CMX were 3.5, 1.7 and 1.9 hours, respectively. The inversion of values obtained between the 2nd and 3rd groups appears to be attributable to that all of the 3rd group were premature infants, and the body weight of 2 cases of them were less than 2,000 g each. Urinary recovery rates ranged widely from 37.0 to 89.4% in the 4 cases examined during the first 6 hours. (3) One-hour intravenous drip infusion of 20 mg/kg: Serum concentrations of the drug in the 3 groups peaked at 57.7, 60.2 and 72.4 micrograms/ml, respectively, all at the termination of the drug infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of di(2-ethylhexyl) phthalate (DEHP)-induced endocrine disruption by co-treatment of vitamins C and E and their mechanism of action.

PubMed

Choi, Seul Min; Lim, Duck Soo; Kim, Min Kook; Yoon, Sungpil; Kacew, Sam; Kim, Hyung Sik; Lee, Byung-Mu

2018-05-29

The endocrine disrupting actions of di(2-ethylhexyl) phthalate (DEHP) on testicular functions are postulated to involve excess free radical generation. Thus the aim of this study was to examine the ability of antioxidant vitamins C and E to prevent DEHP-induced testicular disruption in male Sprague-Dawley (SD) rats. SD male rats were administered DEHP alone or DEHP with vitamin C and/or vitamin E for 30 days. DEHP alone increased the levels of testosterone (T) and reduced estradiol (E 2 ) concentrations. Supplementation with antioxidant vitamins diminished or restored serum T levels noted in DEHP-treated rats to control values. In contrast vitamins C and E increased E 2 levels to control in rats administered DEHP. Antioxidants significantly improved the decreased testicular levels of reduced glutathione and activity of superoxide dismutase compared to DEHP-treatment alone. Co-treatment of vitamins C and E also markedly improved the reduced epididymal sperm head counts and elevated levels of malondialdehyde (MDA) or 8-hydroxydeoxyguanosine (8-OHdG) induced by DEHP treatment. These results support the concept that the adverse actions of DEHP may be related to increased free radical generation while co-treatment with vitamins C and E significantly blocked the actions of DEHP on male testicular functions.

Childhood trauma and parental style: Relationship with markers of inflammation, oxidative stress, and aggression in healthy and personality disordered subjects.

PubMed

Fanning, Jennifer R; Lee, Royce; Gozal, David; Coussons-Read, Mary; Coccaro, Emil F

2015-12-01

Recent studies suggest that early life trauma is associated with elevations in circulating markers of inflammation in human subjects. History of aggression as a behavior, or aggression as a personality trait, is also associated with elevations of these inflammatory markers. Since early life trauma is associated with the development and maintenance of aggression in later life we examined the relationship of early life adversity, plasma inflammation markers (IL-6 and CRP) and oxidative stress markers (8-OH-DG and 8-ISO), and aggression in adult subjects with (n=79) and without (n=55) personality disorder. We used a series of mediated and moderated path models to test whether the effects of early adversity on later aggression may be mediated through markers of inflammation. Childhood abuse and parental control were associated with basal IL-6 and CRP concentrations. Path modeling suggested that childhood abuse was associated with aggression indirectly through CRP while parental control influenced aggression indirectly through IL-6 and CRP. Furthermore, these effects were independent of the effect of current depression. The results suggest that disruption of inflammatory processes represent one pathway by which early adversity influences aggression. Copyright © 2015 Elsevier B.V. All rights reserved.

Formononetin attenuates hydrogen peroxide (H2O2)-induced apoptosis and NF-κB activation in RGC-5 cells.

PubMed

Jia, W-C; Liu, G; Zhang, C-D; Zhang, S-P

2014-01-01

Diabetic retinopathy is a common diabetic eye disease caused by changes in retinal ganglion cells (RGCs). Several studies suggest that the oxidative stress plays a role in the pathogenesis of diabetic retinopathy in adults. Formononetin is a flavone with powerful antioxidant properties that exists naturally in various plants and Chinese medicine. In the present study, an attempt has been made to investigate the antioxidative effects of formononetin on H2O2-induced apoptosis of RGC-5 cells. Exposure of retinal ganglion cells (RGCs) to the indicated concentrations of formononetin and H2O2 for 24 h, analyzed by MTT assay. Cells were stained with Annexin V-FITC and PI, analyzed by flow cytometry. And the level of superoxide anions, malondialdehyde (MDA, a marker of lipid peroxidation), 8-hydroxy-2-deoxyguanosine (8-OHdG, indicator of oxidative DNA damage) and MnSOD (manganese superoxide dismutase) activity were measured by kits. Formononetin reduced hydrogen peroxide (H2O2)-induced apoptosis and improved the levels or activity of indicators of oxidative stress. Formononetin also inhibited the activation of nuclear factor-kappaB (NF-κB), which is a significant transcription factor for RGC-5 apoptosis. Formononetin may be developed as a antioxidant drug to treat diabetic retinopathy.

Urinary corticosterone metabolite responses to capture and captivity in the cane toad (Rhinella marina).

PubMed

Narayan, Edward J; Cockrem, John F; Hero, Jean-Marc

2011-09-01

Urinary corticosterone metabolite responses to capture have recently been shown for the first time in amphibians, and in the present study urinary corticosterone metabolite responses to capture and to confinement in captivity were measured in adult cane toads (Rhinella marina) in Queensland, Australia. An adrenocorticotropic hormone (ACTH) challenge was used to provide a biological validation for urinary corticosterone metabolite concentrations measured by radioimmunoassay (RIA). Urinary corticosterone metabolite increased 1-2 days after ACTH but not saline injection and then returned to initial values, indicating that the RIA could detect changes in corticosterone secretion in toads. Urinary corticosterone metabolite responses to short-term capture and restraint in plastic bags were first apparent 2h after capture of wild toads. Toads held communally in captivity for 5 days had elevated urinary corticosterone metabolite concentrations. Mean corticosterone concentrations declined significantly after a further 7 days in individual housing chambers. There was no sex difference in urinary corticosterone metabolite responses of toads to ACTH challenge, short-term capture or captivity. The relative amount of variation in the mean corticosterone responses was quantified by calculating coefficients of variation (CV) for each mean corticosterone response. Mean corticosterone at 0 min was more variable for captive toads than wild toads. Furthermore, initial corticosterone concentrations (0 min) were more variable than concentrations during the ACTH challenge, short-term capture and captivity. There was little change in the amount of variation of mean corticosterone levels between male and female toads with increasing time in captivity (12-29 days). This study has shown individual corticosterone responses of amphibians for the first-time, and has provided a novel method for quantifying the relative amount of variation in amphibian corticosterone responses. Copyright © 2011 Elsevier Inc. All rights reserved.

Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

PubMed

Armstrong, Eliana S; Mikulca, Janelle A; Cloutier, Daniel J; Bliss, Caleb A; Steenbergen, Judith N

2016-11-25

Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an opportunity to test this hypothesis by examining the clinical and microbiological outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory concentration. Patients were randomly assigned 1:1 to ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided data on 370 patients with at least one isolate of Enterobacteriaceae at baseline who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5-9 days after treatment) and late follow-up (21-42 days after treatment) visits in the microbiologically evaluable population (N = 327). Test-of-cure clinical cure rates above 90% were observed at minimum inhibitory concentrations ≤4 μg/mL. Microbiological eradication rates were consistently >90% at levofloxacin minimum inhibitory concentrations ≤0.06 μg/mL. Lack of eradication of causative pathogens at the test-of-cure visit increased the likelihood of relapse by the late follow-up visit. Results from this study do not support levofloxacin therapy for complicated urinary tract infections caused by organisms with levofloxacin minimum inhibitory concentrations ≥4 μg/mL. ClinicalTrials.gov, NCT01345929 and NCT01345955.

Urinary paracetamol and time-to-pregnancy

PubMed Central

Smarr, Melissa M.; Grantz, Katherine L.; Sundaram, Rajeshwari; Maisog, José M.; Honda, Masato; Kannan, Kurunthachalam; Buck Louis, Germaine M.

2016-01-01

STUDY QUESTION Is preconception urinary paracetamol (acetaminophen) associated with time-to-pregnancy (TTP)? SUMMARY ANSWER Higher urinary paracetamol concentrations among male partners were associated with a longer TTP. WHAT IS KNOWN ALREADY Paracetamol is a commonly used analgesic among women and men of all ages. As metabolites of select chemicals used in the manufacturing of polyurethane foam, dyes and various industrial products, as well as a common medicinal product, paracetamol and its primary metabolite p-aminophenol, are ubiquitous in the environment. Studies investigating the relationship between adult urinary concentrations of paracetamol and TTP are lacking. STUDY DESIGN, SIZE, DURATION This prospective cohort included 501 couples discontinuing contraception for the purposes of attempting conception during the years 2005–2009 and residing in Michigan or Texas, USA. PARTICIPANTS/MATERIALS, SETTING, METHODS Total urinary paracetamol, its metabolite para-aminophenol (p-aminophenol), and a summary measure of both urinary biomarkers were quantified by ultra-performance liquid chromatography coupled with an electrospray triple quadrupole mass spectrometry (UPLC-ESI-MS/MS). Female partners used the Clearblue® digital home test to confirm pregnancy. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs), adjusting for age, body mass index (BMI), urinary creatinine, preconception smoking status, race/ethnicity and household income. Models were further adjusted for hypothyroidism and hypertension as an attempt to account for possible indications of paracetamol medication use. FOR estimates <1.0 denote a longer TTP (diminished fecundity). Models were performed to examine urinary concentrations of paracetamol as a continuous and variable or categorized into quartiles. In light of TTP being a couple-dependent outcome, models were first performed for females and males, modeled separately, and then modeled for couples with each partner's concentrations being adjusted for the other. MAIN RESULTS AND THE ROLE OF CHANCE Among the 501 enrolled couples, 347 (69%) had an human chorionic gonadotrophin confirmed pregnancy. Urinary concentrations of paracetamol were lowest among females and males who achieved pregnancy and p-aminophenol concentrations were lowest among those not achieving pregnancy. Urinary paracetamol concentrations were higher among female than male partners (Median = 26.6 and 13.2 ng/ml, respectively; P < 0.0001). After adjustment for age, BMI, urinary creatinine, preconception smoking status, race/ethnicity and household income, the highest quartile of male urinary paracetamol was associated with a longer TTP [FOR = 0.67; 95% CI = (0.47, 0.95)]. This association remained after adjustment for chronic health conditions, hypothyroidism and hypertension and female partner's urinary paracetamol concentration [FOR = 0.65; 95% CI = (0.45, 0.94)]. No associations were observed between female or male partners' urinary concentrations of paracetamol or of its metabolite p-aminophenol when urinary concentrations were modeled continuously. LIMITATIONS, REASONS FOR CAUTION Only a single spot urine was available for analysis despite the short-lived nature of paracetamol. Additionally, participants were not asked to provide information on indication of use for paracetamol medications; any underlying conditions for the paracetamol use would have been potential confounders. WIDER IMPLICATIONS OF THE FINDINGS If corroborated with more robust studies, findings from our exploratory analysis may have both clinical and public health relevance among reproductive aged individuals, including those trying for pregnancy, given the prevalent use of paracetamol/acetaminophen medications and the ubiquitous nature of paracetamol in the environment. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the National Institutes of Health, Intramural Research Program, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355; N01-HD-3-3356; NOH-HD-3-3358; HHSN27500001/HHSN27500001). None of the authors have any conflicts to declare. PMID:27412248

Urinary paracetamol and time-to-pregnancy.

PubMed

Smarr, Melissa M; Grantz, Katherine L; Sundaram, Rajeshwari; Maisog, José M; Honda, Masato; Kannan, Kurunthachalam; Buck Louis, Germaine M

2016-09-01

Is preconception urinary paracetamol (acetaminophen) associated with time-to-pregnancy (TTP)? Higher urinary paracetamol concentrations among male partners were associated with a longer TTP. Paracetamol is a commonly used analgesic among women and men of all ages. As metabolites of select chemicals used in the manufacturing of polyurethane foam, dyes and various industrial products, as well as a common medicinal product, paracetamol and its primary metabolite p-aminophenol, are ubiquitous in the environment. Studies investigating the relationship between adult urinary concentrations of paracetamol and TTP are lacking. This prospective cohort included 501 couples discontinuing contraception for the purposes of attempting conception during the years 2005-2009 and residing in Michigan or Texas, USA. Total urinary paracetamol, its metabolite para-aminophenol (p-aminophenol), and a summary measure of both urinary biomarkers were quantified by ultra-performance liquid chromatography coupled with an electrospray triple quadrupole mass spectrometry (UPLC-ESI-MS/MS). Female partners used the Clearblue® digital home test to confirm pregnancy. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs), adjusting for age, body mass index (BMI), urinary creatinine, preconception smoking status, race/ethnicity and household income. Models were further adjusted for hypothyroidism and hypertension as an attempt to account for possible indications of paracetamol medication use. FOR estimates <1.0 denote a longer TTP (diminished fecundity). Models were performed to examine urinary concentrations of paracetamol as a continuous and variable or categorized into quartiles. In light of TTP being a couple-dependent outcome, models were first performed for females and males, modeled separately, and then modeled for couples with each partner's concentrations being adjusted for the other. Among the 501 enrolled couples, 347 (69%) had an human chorionic gonadotrophin confirmed pregnancy. Urinary concentrations of paracetamol were lowest among females and males who achieved pregnancy and p-aminophenol concentrations were lowest among those not achieving pregnancy. Urinary paracetamol concentrations were higher among female than male partners (Median = 26.6 and 13.2 ng/ml, respectively; P < 0.0001). After adjustment for age, BMI, urinary creatinine, preconception smoking status, race/ethnicity and household income, the highest quartile of male urinary paracetamol was associated with a longer TTP [FOR = 0.67; 95% CI = (0.47, 0.95)]. This association remained after adjustment for chronic health conditions, hypothyroidism and hypertension and female partner's urinary paracetamol concentration [FOR = 0.65; 95% CI = (0.45, 0.94)]. No associations were observed between female or male partners' urinary concentrations of paracetamol or of its metabolite p-aminophenol when urinary concentrations were modeled continuously. Only a single spot urine was available for analysis despite the short-lived nature of paracetamol. Additionally, participants were not asked to provide information on indication of use for paracetamol medications; any underlying conditions for the paracetamol use would have been potential confounders. If corroborated with more robust studies, findings from our exploratory analysis may have both clinical and public health relevance among reproductive aged individuals, including those trying for pregnancy, given the prevalent use of paracetamol/acetaminophen medications and the ubiquitous nature of paracetamol in the environment. This research was supported by the National Institutes of Health, Intramural Research Program, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355; N01-HD-3-3356; NOH-HD-3-3358; HHSN27500001/HHSN27500001). None of the authors have any conflicts to declare. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Renal function in sheep during infusion of alkali metal ions into the renal artery.

PubMed Central

Beal, A M; Harrison, F A

1975-01-01

1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron. PMID:236381

Urinary concentrations of environmental phenols in pregnant women in a pilot study of the National Children's Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mortensen, Mary E., E-mail: MMortensen@cdc.gov; Calafat, Antonia M.; Ye, Xiaoyun

Environmental phenols are a group of chemicals with widespread uses in consumer and personal care products, food and beverage processing, and in pesticides. We assessed exposure to benzophenone-3, bisphenol A (BPA), triclosan, methyl- and propyl parabens, and 2,4- and 2,5-dichlorophenol or their precursors in 506 pregnant women enrolled in the National Children's Study (NCS) Vanguard Study. We measured the urinary concentrations of the target phenols by using online solid-phase extraction–isotope dilution high performance liquid chromatography–tandem mass spectrometry. NCS women results were compared to those of 524 similar-aged women in the National Health and Nutrition Examination Survey (NHANES) 2009–2010, and tomore » 174 pregnant women in NHANES 2005–2010. In the NCS women, we found significant racial/ethnic differences (p<0.05) in regression adjusted mean concentrations of benzophenone-3, triclosan, 2,4- and 2,5-dichlorophenol, but not of BPA. Urinary 2,4- and 2,5-dichlorophenol concentrations were highly correlated (r=0.66, p<0.0001). Except for BPA and triclosan, adjusted mean concentrations were significantly different across the 7 study sites. Education was marginally significant for benzophenone-3, triclosan, propyl paraben, and 2,5-dichlorophenol. Urinary concentrations of target phenols in NCS pregnant women and U.S. women and pregnant women were similar. In NCS pregnant women, race/ethnicity and geographic location determined urinary concentrations of most phenols (except BPA), suggesting differential exposures. NCS Main Study protocols should collect urine biospecimens and information about exposures to environmental phenols. - Highlights: • Limited biomonitoring data are available in pregnant women. • Seven urinary phenols were measured in 506 third trimester women enrolled in the NCS. • Urine benzophenone-3, triclosan, 2,4- and 2,5-dichlorophenol differed by race/ethnicity. • Urinary concentrations of 2,4- and 2,5-dichlorophenol were highly correlated. • Exposure information can expand the utility of biospecimens in the NCS Main Study.« less