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Sample records for increased oxidative stress

  1. Futile cycling increases sensitivity toward oxidative stress in Escherichia coli

    PubMed Central

    Adolfsen, Kristin J.; Brynildsen, Mark P.

    2015-01-01

    Reactive oxygen species (ROS) are toxic molecules utilized by the immune system to combat invading pathogens. Recent evidence suggests that inefficiencies in ATP production or usage can lead to increased endogenous ROS production and sensitivity to oxidative stress in bacteria. With this as inspiration, and knowledge that ATP is required for a number of DNA repair mechanisms, we hypothesized that futile cycling would be an effective way to increase sensitivity to oxidative stress. We developed a mixed integer linear optimization framework to identify experimentally-tractable futile cycles, and confirmed metabolic modeling predictions that futile cycling depresses growth rate, and increases both O2 consumption and ROS production per biomass generated. Further, intracellular ATP was decreased and sensitivity to oxidative stress increased in all actively cycling strains compared to their catalytically inactive controls. This research establishes a fundamental connection between ATP metabolism, endogenous ROS production, and tolerance toward oxidative stress in bacteria. PMID:25732623

  2. [Relationship of bilirubin to diseases caused by increased oxidative stress].

    PubMed

    Vítek, L

    2013-07-01

    Oxidative stress contributes importantly to pathogenesis of numerous civilization diseases, including cardiovascular diseases, cancer, as well as autoimmune and neurodegenerative conditions. Bilirubin is the major product of the heme catabolic pathway in the intravascular compartment. For long time, bilirubin was considered to be only a waste product, however, recent data from the last 2 decades have proved its important antioxidant properties, which contributes to defense against increased oxidative stress. Numerous experimental as well as clinical studies have demonstrated association between low bilirubin concentrations and cardiovascular diseases, diabetes, certain cancers, autoimunne diseases, such as lupus erythematodes, or rheumatoid arthritis or neurological psychiatric disorders, such as schizofrenia. On the other hand, subjects with mildly elevated blood bilirubin levels, typical for Gilbert syndrome, have decreased risk of these diseases.

  3. Increased oxidative stress in barn swallows from the Chernobyl region.

    PubMed

    Bonisoli-Alquati, Andrea; Mousseau, Timothy A; Møller, Anders Pape; Caprioli, Manuela; Saino, Nicola

    2010-02-01

    The Chernobyl nuclear accident produced the largest unintended release of radionuclides in history, with dramatic consequences for humans and other organisms. Exposure to ionizing radiation is known to reduce circulating and stored levels of specific antioxidants in birds and humans, thus potentially increasing oxidative stress. However, overall effects of radioactive exposure on oxidative status have never been investigated in any free ranging vertebrate. We measured plasma antioxidant capacity and concentration of reactive oxygen metabolites in adult barn swallows (Hirundo rustica) from colonies with variable background radiation levels in the Chernobyl region in Ukraine and Belarus. We predicted that antioxidants would decrease while reactive oxygen metabolites would increase with exposure to increasing levels of radiation at the breeding sites. Consistent with this expectation, radiation level positively predicted plasma concentration of reactive oxygen metabolites, whereas no significant covariation was found with non-enzymatic plasma antioxidant capacity. An index of oxidative stress was also larger in barn swallows exposed to high contamination levels. Thus, radioactive contamination appeared to be responsible for the increased generation of reactive oxygen metabolites and the imbalance between reactive oxygen metabolites and non-enzymatic plasma antioxidant capacity. 2009 Elsevier Inc. All rights reserved.

  4. Increased oxidative stress and oxidative DNA damage in non-remission schizophrenia patients.

    PubMed

    Sertan Copoglu, U; Virit, Osman; Hanifi Kokacya, M; Orkmez, Mustafa; Bulbul, Feridun; Binnur Erbagci, A; Semiz, Murat; Alpak, Gokay; Unal, Ahmet; Ari, Mustafa; Savas, Haluk A

    2015-09-30

    Increasing evidence shows that oxidative stress plays a role in the pathophysiology of schizophrenia. But there is not any study which examines the effects of oxidative stress on DNA in schizophrenia patients. Therefore we aimed to assess the oxidative stress levels and oxidative DNA damage in schizophrenia patients with and without symptomatic remission. A total of 64 schizophrenia patients (38 with symptomatic remission and 26 without symptomatic remission) and 80 healthy volunteers were included in the study. 8-hydroxydeoxyguanosine (8-OHdG), total oxidant status (TOS) and total antioxidant status (TAS) were measured in plasma. TOS, oxidative stress index (OSI) and 8-OHdG levels were significantly higher in non-remission schizophrenic (Non-R-Sch) patients than in the controls. TOS and OSI levels were significantly higher in remission schizophrenic (R-Sch) patients than in the controls. TAS level were significantly lower and TOS and OSI levels were significantly higher in R-Sch patients than in Non-R-Sch patients. Despite the ongoing oxidative stress in patients with both R-Sch and Non-R-Sch, oxidative DNA damage was higher in only Non-R-Sch patients compared to controls. It is suggested that oxidative stress can cause the disease via DNA damage, and oxidative stress plays a role in schizophrenia through oxidative DNA damage.

  5. Increased oxidative stress parameters in children with moderate iodine deficiency.

    PubMed

    Kurku, Huseyin; Gencer, Ali; Pirgon, Ozgur; Buyukinan, Muammer; Aslan, Nagehan

    2016-10-01

    Iodine is a part of thyroid hormones and has been reported to act directly as an antioxidant or induce indirectly antioxidant enzymes. This study aimed to assess the urinary iodine concentration and its relationship between the antioxidant and oxidative stress capacity in healthy school-aged children. In total, 196 students from five primary schools, randomly selected between 9 and 12 years (mean age: 10.2±1.2 years), were enrolled in the study. Urinary iodine levels were measured by spectrophotometry with the Sandell-Kolthoff reaction. Total antioxidant status (TAS) and total oxidant status (TOS) were analysed from urine samples. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of oxidative status. Fifty-four percentage (107) of the children had iodine deficiency (ID) and the majority of them (30%) had mild ID. There was no severe-ID child in the population (<20 μg/L). Urine TAS levels were significantly lower in the moderate-ID group than in the mild-ID group (6.5±4.1 vs. 11.3±4.1 mmol, p<0.001) and the iodine-sufficient group (11.0±5.3 μmol, p<0.001). TOS levels and OSI were found higher in the moderate-ID group than in the mild-ID group (4.8±2.1 vs. 3.7±2.1 μmol, p<0.001) and the iodine-sufficient group (4.8±2.1 vs. 3.4±2.5 mmol, p<0.001). In the moderate-ID group, low urine iodine levels exhibited significant negative correlations with OSI (r=-0.660) and TOS (r=-0.248) and a positive correlation with TAS (r=0.475). We found that children with moderate ID were exposed to more oxidative burden than children with mild ID or iodine sufficiency. Increased systemic oxidative stress induced by moderate ID could cause development of ID-related complications and diseases. Iodine supplementation could have a beneficial role in the prevention of oxidative stress.

  6. Overloaded training increases exercise-induced oxidative stress and damage.

    PubMed

    Palazzetti, Stephane; Richard, Marie-Jeanne; Favier, Alain; Margaritis, Irene

    2003-08-01

    We hypothesized that overloaded training (OT) in triathlon would induce oxidative stress and damage on muscle and DNA. Nine male triathletes and 6 male sedentary subjects participated in this study. Before and after a 4-week OT, triathletes exercised for a duathlon. Blood ratio of reduced vs. oxidized glutathione (GSH/GSSG), plasma thiobarbituric acid reactive substances (TBARS), leukocyte DNA damage, creatine kinase (CK), and CK-MB mass in plasma, erythrocyte superoxide dismutase (SOD) activity, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, and plasma total antioxidant status (TAS) were measured before and after OT in pre- and postexercise situations. Triathletes were overloaded in response to OT. In rest conditions, OT induced plasma GSH-Px activity increase and plasma TAS decrease (both p < 0.05). In exercise conditions, OT resulted in higher exercise-induced variations of blood GSH/GSSG ratio, TBARS level (both p < 0.05), and CK-MB mass (p < 0.01) in plasma; and decreased TAS response (p < 0.05). OT could compromise the antioxidant defense mechanism with respect to exercise-induced response. The resulting increased exercise-induced oxidative stress and further cellular susceptibility to damage needs more study.

  7. Increased oxidative stress and impaired antioxidant response in Lafora disease.

    PubMed

    Romá-Mateo, Carlos; Aguado, Carmen; García-Giménez, José Luis; Ibáñez-Cabellos, José Santiago; Seco-Cervera, Marta; Pallardó, Federico V; Knecht, Erwin; Sanz, Pascual

    2015-01-01

    Lafora disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains largely unknown. Since autophagy impairment has been reported as a characteristic treat in both Lafora disease cell and animal models, and as there is a link between autophagy and mitochondrial performance, we sought to determine if mitochondrial function could be altered in those models. Using fibroblasts from LD patients, deficient in laforin or malin, we found mitochondrial alterations, oxidative stress and a deficiency in antioxidant enzymes involved in the detoxification of reactive oxygen species (ROS). Similar results were obtained in brain tissue samples from transgenic mice deficient in either the EPM2A or EPM2B genes. Furthermore, in a proteomic analysis of brain tissue obtained from Epm2b-/- mice, we observed an increase in a modified form of peroxiredoxin-6, an antioxidant enzyme involved in other neurological pathologies, thus corroborating an alteration of the redox condition. These data support that oxidative stress produced by an increase in ROS production and an impairment of the antioxidant enzyme response to this stress play an important role in development of LD.

  8. Burn Serum Increases Staphylococcus aureus Biofilm Formation via Oxidative Stress

    PubMed Central

    Yin, Supeng; Jiang, Bei; Huang, Guangtao; Gong, Yali; You, Bo; Yang, Zichen; Chen, Yu; Chen, Jing; Yuan, Zhiqiang; Li, Ming; Hu, Fuquan; Zhao, Yan; Peng, Yizhi

    2017-01-01

    Staphylococcus aureus is a common pathogen isolated from burn patients that can form biofilms on burn wounds and implanted deep vein catheters, which often leads to refractory infections or even biofilm-related sepsis. As biofilm formation is usually regulated by environmental conditions, we hypothesized that serum composition may be altered after burn injury, potentially affecting the ability of infecting bacteria to form biofilms. As predicted, we observed that serum from burn-injured rats increases biofilm formation by S. aureus and also induces bacterial aggregation and adherence to human fibronectin and fibrinogen. Analysis of potential regulatory factors revealed that exposure to burn serum decreases expression of the quorum-sensing agr system and increases mRNA levels of some biofilm inducers such as sarA and icaA. In addition, we also observed that burn serum imposes oxidative stress and increases expression of key oxidoreductase genes (sodA, sodM, katA, and ahpC) in S. aureus. Importantly, the ability of burn serum to enhance biofilm formation and bacterial cell aggregation can be abrogated by treatment with an antioxidant. Taken together, these findings indicate that burn serum increases S. aureus biofilm formation via elevated oxidative stress, and may lead to novel strategies to control biofilm formation and infection in burn patients. PMID:28702016

  9. Increased Oxidative Stress as a Selective Anticancer Therapy

    PubMed Central

    2015-01-01

    Reactive oxygen species (ROS) are closely related to tumorgenesis. Under hypoxic environment, increased levels of ROS induce the expression of hypoxia inducible factors (HIFs) in cancer stem cells (CSCs), resulting in the promotion of the upregulation of CSC markers, and the reduction of intracellular ROS level, thus facilitating CSCs survival and proliferation. Although the ROS level is regulated by powerful antioxidant defense mechanisms in cancer cells, it is observed to remain higher than that in normal cells. Cancer cells may be more sensitive than normal cells to the accumulation of ROS; consequently, it is supposed that increased oxidative stress by exogenous ROS generation therapy has an effect on selectively killing cancer cells without affecting normal cells. This paper reviews the mechanisms of redox regulation in CSCs and the pivotal role of ROS in anticancer treatment. PMID:26273420

  10. Oxidative stress increased in pregnant women with iodine deficiency.

    PubMed

    Vidal, Zendy Evelyn Olivo; Rufino, Sergio Cuellar; Tlaxcalteco, Esteban Hernández; Trejo, Cirenia Hernández; Campos, Raúl Martínez; Meza, Mónica Navarro; Rodríguez, Rocío Coutiño; Arroyo-Helguera, Omar

    2014-03-01

    Iodine is an essential element trace for the synthesis of maternal thyroid hormones needed to support normal fetal development; it also acts as an antioxidant directly or induce antioxidant enzymes indirectly. Iodine deficiency and oxidative stress are associated with pregnancy complications. This study aimed to assess the urinary iodine concentration and its relationship with the antioxidant and oxidative stress status during gestation. Pregnant women were consecutively recruited from an obstetric clinic during all gestation trimesters, and urinary iodine concentration, antioxidant, and oxidative stress were determined. Results showed that 70 % of pregnant women have optimal iodine levels (150-200 μg/L), while approximately 30 % showed mild iodine deficiency (50-99 μg/L). Oxidative stress was significantly higher, and the antioxidant status was also compromised as evidenced by decreased total antioxidant status and superoxide dismutase (SOD) activity in pregnant women with mild iodine deficiency than pregnant women with optimal iodine levels. Significant positive correlations were noted between optimal iodine levels and total antioxidant status. Oxidative stress was significantly correlated with mild iodine deficiency. However, no significant correlation was found between iodine levels and SOD and catalase activities. In conclusion, for the first time, these data suggest a correlation between iodine levels and the antioxidant status during pregnancy.

  11. Increased systemic oxidative stress in patients with keratoconus.

    PubMed

    Toprak, I; Kucukatay, V; Yildirim, C; Kilic-Toprak, E; Kilic-Erkek, O

    2014-03-01

    To establish the effect of systemic oxidative stress on the pathogenesis of keratoconus by measuring serum total oxidant status (TOS) and total antioxidant status (TAS) in patients with keratoconus. Twenty-five patients with keratoconus (keratoconus group) and 25 age-sex-matched healthy subjects (control group) were enrolled in the study. Exclusion criteria were smoking habit, history of any other corneal pathology, systemic disease or inflammation, and current antioxidant or anti-inflammatory therapies. All participants underwent a detailed ophthalmological examination and corneal topography. Serum samples were obtained from all participants. Oxidative stress markers (TAS and TOS) were measured using a commercial kit and oxidative stress index (OSI) was calculated. The study comprised 25 patients with keratoconus (mean age of 26.4±1.7 years) and 25 healthy control subjects (mean age of 26.6±1.7 years) (P>0.05). The serum TOS and OSI values were significantly higher in patients with keratoconus compared with those of the controls (P=0.036 and 0.037, respectively). However, serum TAS did not show significant difference between the keratoconus and control groups (P=0.497). The higher levels of serum oxidant status and OSI in patients with keratoconus suggest that systemic oxidative stress might be involved in the pathogenesis of keratoconus.

  12. Maternal obesity increases oxidative stress in the newborn.

    PubMed

    Gallardo, Juan Manuel; Gómez-López, Jaqueline; Medina-Bravo, Patricia; Juárez-Sánchez, Francisco; Contreras-Ramos, Alejandra; Galicia-Esquivel, Matilde; Sánchez-Urbina, Rocío; Klünder-Klünder, Miguel

    2015-08-01

    Obesity before pregnancy is associated with a greater risk for the offspring to develop obesity and diabetes in childhood and adulthood. The aim of the present study was to determine the association between maternal overweight or obesity before pregnancy and newborn oxidative stress (OS). Seventy-two mother-child pairs were divided according to the pre-gestational body mass index (BMI) of the mothers as follows: eutrophic (n = 21), overweight (n = 32), and obese (n = 19). Malondialdehyde (MDA) and nitric oxide (NO) were measured in the plasma of a blood sample from the newborn's umbilical cord. The MDA levels of newborns increased with maternal BMI (P = 0.001), as did the levels of NO (P = 0.019). There was a direct correlation between MDA and NO levels in each of the three groups (eutrophic: R(2)  = 0.59, P < 0.001; overweight: R(2)  = 0.45, P < 0.001; and obese: R(2)  = 0.26, P = 0.024). Maternal overweight and obesity before pregnancy are associated with increased OS in the offspring. © 2015 The Obesity Society.

  13. Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells

    SciTech Connect

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada; Quaroni, Andrea; Autore, Giuseppina; Severino, Lorella; Marzocco, Stefania

    2015-06-01

    Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. - Highlights: • Nivalenol induces oxidative stress in intestinal epithelial cells (IECs). • Nivalenol increases deoxynivalenol pro-oxidant effects in IECs. • Nivalenol and deoxynivalenol trigger antioxidant response IECs. • These results indicate the importance of mycotoxins co-contamination.

  14. Total oxidant status and oxidative stress are increased in infants with necrotizing enterocolitis.

    PubMed

    Aydemir, Cumhur; Dilli, Dilek; Uras, Nurdan; Ulu, Hulya Ozkan; Oguz, Serife Suna; Erdeve, Omer; Dilmen, Ugur

    2011-11-01

    Oxidative stress has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). In this study, we compared the global oxidant/antioxidant status by measuring total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in preterm infants with NEC and with control preterms. Forty-one preterm neonates with NEC (stage 1 [group 1; n = 23] and stages 2 and 3 [group 2; n = 18]) and age-matched 36 healthy preterm controls (group 3) were included in this study. Blood samples were obtained both at the time of NEC diagnosis and 72 hours after for the evaluation of TAC and TOS. Serum levels of TAC, TOS, and OSI in patients with NEC were compared with controls. Demographic characteristics were comparable in all 3 groups. Preterm neonates in group 2 (with stages 2 and 3 NEC) had the highest TOS levels and OSI (P < .001 vs both groups 1 and 3). There was no difference in TAC levels among the groups (P = .26). Our findings demonstrated that although TAC levels were similar in all 3 groups, oxidant stress mechanisms were activated in preterm neonates with definite NEC (stages 2 and 3 NEC). Premature neonates with increased levels of TOS and OSI were associated with severity of NEC. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    SciTech Connect

    Mazière, Cécile; Salle, Valéry; Gomila, Cathy; Mazière, Jean-Claude

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  16. Increased oxidative stress in pemphigus vulgaris is related to disease activity and HLA-association.

    PubMed

    Shah, Amit Aakash; Dey-Rao, Rama; Seiffert-Sinha, Kristina; Sinha, Animesh A

    2016-06-01

    Pemphigus vulgaris (PV) is a rare blistering skin disorder characterized by the disadhesion of keratinocytes due to autoantibody attack against epidermal targets including desmoglein (Dsg) 3, Dsg 1 and possibly other adhesion and non-adhesion molecules. The mechanisms leading to immune-mediated pathology in PV are multifactorial and not fully understood. Recently, oxidative stress (antioxidant/oxidant disequilibrium) has been proposed as a contributory mechanism of autoimmune skin diseases, including PV. In this study, we directly assessed oxidative stress via measurement of total antioxidant capacity (TAC) using ELISA in 47 PV patients, 25 healthy controls and 18 bullous pemphigoid (BP) patients. We also performed microarray gene expression analysis on a separate set of 21 PV patients and 10 healthy controls to evaluate transcriptional dysregulation in oxidative stress-related pathways. Our data indicate that there is a significant reduction in TAC levels in PV patients compared with healthy controls, as well as BP patients. Furthermore, PV patients with active disease have significantly lower TAC levels than PV patients in remission. We also find that HLA allele status has a significant influence on oxidative stress. These findings are corroborated by microarray analysis showing differentially expressed genes involved in oxidative stress between the aforementioned groups. Collectively, our findings provide support for a role of oxidative stress in PV. Whether increased oxidative stress leads to disease manifestation and/or activity, or if disease activity leads to increased oxidative stress remains unknown. Future longitudinal studies may help to further elucidate the relationship between PV and oxidative stress.

  17. Financial strain is associated with increased oxidative stress levels: the Women's Health and Aging Studies.

    PubMed

    Palta, Priya; Szanton, Sarah L; Semba, Richard D; Thorpe, Roland J; Varadhan, Ravi; Fried, Linda P

    2015-01-01

    Elevated oxidative stress levels may be one mechanism contributing to poor health outcomes. Financial strain and oxidative stress are each predictors of morbidity and mortality, but little research has investigated their relationship. Community-dwelling older adults (n = 728) from the Women's Health and Aging Studies I and II were included in this cross-sectional analysis. Financial strain was ascertained as an ordinal response to: "At the end of the month, do you have more than enough money left over, just enough, or not enough?" Oxidative stress was measured using serum protein carbonyl concentrations. Linear regression was used to quantify the relationship between financial strain and oxidative stress. Participants who reported high financial strain exhibited 13.4% higher protein carbonyl concentrations compared to individuals who reported low financial strain (p = 0.002). High financial strain may be associated with increased oxidative stress, suggesting that oxidative stress could mediate associations between financial strain and poor health.

  18. Carvedilol inhibits pressure-induced increase in oxidative stress in coronary smooth muscle cells.

    PubMed

    Yasunari, Kenichi; Maeda, Kensaku; Nakamura, Munehiro; Yoshikawa, Junichi

    2002-05-01

    The cellular mechanisms by which hypertension enhances atherosclerosis are still not known in detail. Recently, evidence has been obtained that oxidative stress plays a role in the pathogenesis of pressure-induced atherosclerosis. We examined the effects of pressure on oxidative stress in cultured human coronary smooth muscle cells (SMCs). Application of increased pressure (+100 mmHg) with He gas for 48 h increased oxidative stress of measured by flow cytometry by 71% and F2-isopretane by 77%. Increased pressure also increased the activities of phospholipase D (PLD), and particulate protein kinase C (PKC). The PLD inhibitor suramin 100 micromol/l, 1-butanol 40 mmol/l, and the PKC inhibitors chelerythrine 1 micromol/l and calphostin C 100 nmol/l and completely blocked the increase in oxidative stress induced by pressure. Carvedilol 1 micromol/l but not propranolol 1 micromol/l blocked pressure-induced increases in oxidative stress in cultured SMCs. These findings suggest that pressure increases oxidative stress and that carvedilol significantly inhibits pressure-induced increase in oxidative stress in cultured human coronary smooth muscle cells.

  19. Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells.

    PubMed

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada; Quaroni, Andrea; Autore, Giuseppina; Severino, Lorella; Marzocco, Stefania

    2015-06-01

    Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Kidney hypoxia, attributable to increased oxygen consumption, induces nephropathy independently of hyperglycemia and oxidative stress.

    PubMed

    Friederich-Persson, Malou; Thörn, Erik; Hansell, Peter; Nangaku, Masaomi; Levin, Max; Palm, Fredrik

    2013-11-01

    Diabetic nephropathy is strongly associated with both increased oxidative stress and kidney tissue hypoxia. The increased oxidative stress causes increased kidney oxygen consumption resulting in kidney tissue hypoxia. To date, it has been difficult to determine the role of kidney hypoxia, per se, for the development of nephropathy. We tested the hypothesis that kidney hypoxia, without confounding factors such as hyperglycemia or elevated oxidative stress, results in nephropathy. To induce kidney hypoxia, dinitrophenol (30 mg per day per kg bodyweight by gavage), a mitochondrial uncoupler that increases oxygen consumption and causes kidney hypoxia, was administered for 30 consecutive days to rats. Thereafter, glomerular filtration rate, renal blood flow, kidney oxygen consumption, kidney oxygen tension, kidney concentrations of glucose and glycogen, markers of oxidative stress, urinary protein excretion, and histological findings were determined and compared with vehicle-treated controls. Dinitrophenol did not affect arterial blood pressure, renal blood flow, glomerular filtration rate, blood glucose, or markers of oxidative stress but increased kidney oxygen consumption, and reduced cortical and medullary concentrations of glucose and glycogen, and resulted in intrarenal tissue hypoxia. Furthermore, dinitrophenol treatment increased urinary protein excretion, kidney vimentin expression, and infiltration of inflammatory cells. In conclusion, increased mitochondrial oxygen consumption results in kidney hypoxia and subsequent nephropathy. Importantly, these results demonstrate that kidney tissue hypoxia, per se, without confounding hyperglycemia or oxidative stress, may be sufficient to initiate the development of nephropathy and therefore demonstrate a new interventional target for treating kidney disease.

  1. Does increased intake of salmon increase markers of oxidative stress in pregnant women? The salmon in pregnancy study.

    PubMed

    García-Rodríguez, Cruz E; Helmersson-Karlqvist, Johanna; Mesa, María Dolores; Miles, Elizabeth A; Noakes, Paul S; Vlachava, Maria; Kremmyda, Lefkothea-Stella; Diaper, Norma D; Godfrey, Keith M; Calder, Philip C; Gil, Angel; Basu, Samar

    2011-12-01

    The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Salmon is a rich source of marine n-3 fatty acids. Since marine n-3 fatty acids may increase oxidative stress, we investigated whether increased salmon consumption could affect markers of oxidative stress in mid and late pregnancy. Urinary 8-iso-prostaglandin F(2α), urinary 8-hydroxy-2'-deoxyguanosine, and plasma lipid peroxide concentrations did not change from week 20 to 38 of pregnancy and were not altered by increased consumption of salmon. Thus, increased intake of salmon during pregnancy does not increase oxidative stress, as judged by the markers of oxidative damage to lipids and DNA measured herein.

  2. Proline metabolism increases katG expression and oxidative stress resistance in Escherichia coli.

    PubMed

    Zhang, Lu; Alfano, James R; Becker, Donald F

    2015-02-01

    The oxidation of l-proline to glutamate in Gram-negative bacteria is catalyzed by the proline utilization A (PutA) flavoenzyme, which contains proline dehydrogenase (PRODH) and Δ(1)-pyrroline-5-carboxylate (P5C) dehydrogenase domains in a single polypeptide. Previous studies have suggested that aside from providing energy, proline metabolism influences oxidative stress resistance in different organisms. To explore this potential role and the mechanism, we characterized the oxidative stress resistance of wild-type and putA mutant strains of Escherichia coli. Initial stress assays revealed that the putA mutant strain was significantly more sensitive to oxidative stress than the parental wild-type strain. Expression of PutA in the putA mutant strain restored oxidative stress resistance, confirming that depletion of PutA was responsible for the oxidative stress phenotype. Treatment of wild-type cells with proline significantly increased hydroperoxidase I (encoded by katG) expression and activity. Furthermore, the ΔkatG strain failed to respond to proline, indicating a critical role for hydroperoxidase I in the mechanism of proline protection. The global regulator OxyR activates the expression of katG along with several other genes involved in oxidative stress defense. In addition to katG, proline increased the expression of grxA (glutaredoxin 1) and trxC (thioredoxin 2) of the OxyR regulon, implicating OxyR in proline protection. Proline oxidative metabolism was shown to generate hydrogen peroxide, indicating that proline increases oxidative stress tolerance in E. coli via a preadaptive effect involving endogenous hydrogen peroxide production and enhanced catalase-peroxidase activity.

  3. Increased Salivary Nitric Oxide and G6PD Activity in Refugees with Anxiety and Stress.

    PubMed

    Gammoh, Omar S; Al-Smadi, Ahmed; Al-Awaida, Wajdy; Badr, Mujtaba M; Qinna, Nidal A

    2016-10-01

    Anxiety and stress are related to physiological changes in humans. Accumulating evidence suggests a cross-talk between psychiatric disorders and oxidative stress. The objective of this study was to compare oxidative stress and defensive antioxidant biomarkers in a group of refugees with acute anxiety and stress with a group of local Jordanians. The Hamilton Anxiety Rating Scale (HAM-A) and the Perceived Stress Scale (PSS) Arabic version were used to assess anxiety and stress respectively. Salivary nitric oxide concentration, glucose-6-phosphate dehydrogenase (G6PD) activity and total salivary protein were compared. As expected, refugees showed higher anxiety and stress scores compared with Jordanians. Also, we report a significant increase in salivary nitric oxide and G6PD activity in the refugee group while total protein concentration did not vary between the two groups. This is the first study that demonstrates an increase in nitric oxide and G6PD activity in the saliva of refugees, thus highlighting their potential role as possible biomarkers in anxiety and stress disorders. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Calcium overload increases oxidative stress in old rat gastrocnemius muscle.

    PubMed

    Capel, F; Demaison, L; Maskouri, F; Diot, A; Buffiere, C; Patureau Mirand, P; Mosoni, L

    2005-09-01

    In order to challenge in vivo muscle Ca2+ homeostasis and analyze consequences on mitochondrial H2O2 release (MHR) and sarcopenia, we injected Ca2+ ionophore A23187 (200 microg/kg, ip) in adult and old rats and measured gastrocnemius mass and mitochondrial Ca2+ content (MCC) using radioactive Ca2+ 48 h after injection. In a second experiment performed in old rats, we measured isocitrate dehydrogenase (ICDH) activity as an index of MCC, MHR, mitochondrial respiration, citrate synthase, COX and antioxydant enzyme activities 24 h after a 150 microg/kg injection. In adult rats, muscle mass and MCC were unchanged by A23187. In old rats, MCC increased 24 h after injection as reflected by a significant increase in ICDH activity; measured MCC tended to increase at 48 h. MHR and Mn-SOD activity were significantly increased at 24 h, and GPX activity was reduced. Muscle mass was unchanged but was negatively correlated with MCC in control and treated old rats. In conclusion, in old rats, A23187 probably induced a mitochondrial Ca2+ overload responsible for the observed increase in MHR without leading to muscle atrophy on a short term basis.

  5. Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo

    PubMed Central

    He, Yuanmin; Li, Shuli; Zhang, Weigang; Dai, Wei; Cui, Tingting; Wang, Gang; Gao, Tianwen; Li, Chunying

    2017-01-01

    In vitiligo, melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis and to the genetic antioxidant defects. Autophagy is a controlled self-digestion process which can protect cells against oxidative damage. However, the exact role of autophagy in vitiligo melanocytes in response to oxidative stress and the mechanism involved are still not clear. To determine the implications of autophagy for melanocyte survival in response to oxidative stress, we first detected the autophagic flux in normal melanocytes exposure to H2O2, and found that autophagy was significantly enhanced in normal melanocytes, for protecting cells against H2O2-induced oxidative damage. Nevertheless, vitiligo melanocytes exhibited dysregulated autophagy and hypersensitivity to H2O2-induced oxidative injury. In addition, we confirmed that the impairment of Nrf2-p62 pathway is responsible for the defects of autophagy in vitiligo melanocytes. Noteworthily, upregulation of the Nrf2-p62 pathway or p62 reduced H2O2-induced oxidative damage of vitiligo melanocytes. Therefore, our data demonstrated that dysregulated autophagy owing to the impairment of Nrf2-p62 pathway increase the sensitivity of vitiligo melanocytes to oxidative stress, thus promote the development of vitiligo. Upregulation of p62-dependent autophagy may be applied to vitiligo treatment in the future. PMID:28186139

  6. Nanoparticle Inhalation Increases Microvascular Oxidative Stress and Compromises Nitric Oxide Bioavailability

    EPA Science Inventory

    We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs are unclear. The purpose of this study was to identify alterations in the production of oxidative stress an...

  7. Nanoparticle Inhalation Increases Microvascular Oxidative Stress and Compromises Nitric Oxide Bioavailability

    EPA Science Inventory

    We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs are unclear. The purpose of this study was to identify alterations in the production of oxidative stress an...

  8. Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle

    NASA Technical Reports Server (NTRS)

    Lawler, John M.; Song, Wook; Demaree, Scott R.; Bloomfield, S. A. (Principal Investigator)

    2003-01-01

    Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.

  9. Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle

    NASA Technical Reports Server (NTRS)

    Lawler, John M.; Song, Wook; Demaree, Scott R.; Bloomfield, S. A. (Principal Investigator)

    2003-01-01

    Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.

  10. Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

    PubMed Central

    Lan, Xiqian; Lederman, Rivka; Eng, Judith M.; Shoshtari, Seyedeh Shadafarin Marashi; Saleem, Moin A.; Malhotra, Ashwani; Singhal, Pravin C.

    2016-01-01

    Background Cigarette smoking plays an important role in the progression of chronic kidney disease (CKD). Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury. Methods To determine the expression of nicotinic acetylcholine receptors (nAChR subunits) in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining. We also studied the effect of nicotine on podocyte nephrin expression, reactive oxygen species (ROS) generation (via DCFDA loading followed by fluorometric analysis), proliferation, and apoptosis (morphologic assays). We evaluated the effect of nicotine on podocyte downstream signaling including phosphorylation of ERK1/2, JNK, and p38 and established causal relationships by using respective inhibitors. We used nAChR antagonists to confirm the role of nicotine on podocyte injury. Results Human podocytes displayed robust mRNA and protein expression of nAChR in vitro studies. In vivo studies, mice renal cortical sections revealed co-localization of nAChRs along with synaptopodin. In vitro studies, nephrin expression in podocyte was decreased by nicotine. Nicotine stimulated podocyte ROS generation; nonetheless, antioxidants such as N-acetyl cysteine (NAC) and TEMPOL (superoxide dismutase mimetic agent) inhibited this effect of nicotine. Nicotine did not modulate proliferation but promoted apoptosis in podocytes. Nicotine enhanced podocyte phosphorylation of ERK1/2, JNK, and p38, and their specific inhibitors attenuated nicotine-induced apoptosis. nAChR antagonists significantly suppressed the effects of nicotine on podocyte. Conclusions Nicotine induces podocyte apoptosis through ROS generation and associated downstream MAPKs signaling. The present study provides

  11. Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer.

    PubMed

    Matsuda, Morihiro; Shimomura, Iichiro

    2013-01-01

    Obesity, especially of the abdominal type, is a health problem that constitutes metabolic syndrome and increases the incidence of various diseases, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Various mechanisms linking obesity to these associated diseases have been postulated. One candidate is oxidative stress, which has been implicated in vascular complications of diabetes and in pancreatic -cell failure in diabetes. Notably, obese people without diabetes also display elevated levels of systemic oxidative stress. In addition, levels of oxidative stress are increased in the adipose tissue in obese mice. Treating obese mice with antioxidant agents attenuates the development of diabetes. In 3T3-L1 adipocytes, increases in reactive oxygen species (ROS) occur with lipid accumulation; the addition of free fatty acids elevates ROS generation further. Thus, adipose tissue represents an important source of ROS; ROS may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. Moreover, the levels of oxidative stress present in several other types of cells or tis-sues, including those in the brain, arterial walls, and tumors, have been implicated in the pathogenesis associated with hypertension, atherosclerosis, and cancer. The increased levels of systemic oxidative stress that occur in obesity may contribute to the obesity-associated development of these diseases. © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  12. Mitochondrial respiratory chain dysfunction variably increases oxidant stress in Caenorhabditis elegans.

    PubMed

    Dingley, Stephen; Polyak, Erzsebet; Lightfoot, Richard; Ostrovsky, Julian; Rao, Meera; Greco, Todd; Ischiropoulos, Harry; Falk, Marni J

    2010-03-01

    Mitochondrial dysfunction and associated oxidant stress have been linked with numerous complex diseases and aging largely by in vitro determination of mitochondria oxidant production and scavenging. We applied targeted in vivo fluorescence analyses of mitochondria-dense pharyngeal tissue in Caenorhabditis elegans to better understand relative mitochondrial effects, particularly on matrix oxidant burden, of respiratory chain complex, MnSOD, and insulin receptor mutants displaying variable longevity. The data demonstrate significantly elevated in vivo matrix oxidant burden in the short-lived complex I mutant, gas-1(fc21), which was associated with limited superoxide scavenging capacity despite robust MnSOD induction, as well as decreased mitochondria content and membrane potential. Significantly increased MnSOD activity was associated with in vivo matrix oxidant levels similar to wild-type in the long-lived respiratory chain complex III mutant, isp-1(qm150). Yet, despite greater superoxide scavenging capacity in the complex III mutant than in the significantly longer-lived insulin receptor mutant, daf-2(e1368), only the former showed modest oxidative stress sensitivity. Furthermore, increased longevity was seen in MnSOD knockout mutants (sod-2(ok1030) and sod-2(gk257)) that had decreased MnSOD scavenging capacity and increased in vivo matrix oxidant burden. Thus, factors beside oxidant stress must underlie RC mutant longevity in C. elegans. This work highlights the utility of the C. elegans model as a tractable means to non-invasively monitor multi-dimensional in vivo consequences of primary mitochondrial dysfunction.

  13. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

    2009-01-01

    Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

  14. Inhibition of Adenylyl Cyclase Type 5 Increases Longevity and Healthful Aging through Oxidative Stress Protection

    PubMed Central

    Vatner, Stephen F.; Pachon, Ronald E.; Vatner, Dorothy E.

    2015-01-01

    Mice with disruption of adenylyl cyclase type 5 (AC5 knockout, KO) live a third longer than littermates. The mechanism, in part, involves the MEK/ERK pathway, which in turn is related to protection against oxidative stress. The AC5 KO model also protects against diabetes, obesity, and the cardiomyopathy induced by aging, diabetes, and cardiac stress and also demonstrates improved exercise capacity. All of these salutary features are also mediated, in part, by oxidative stress protection. For example, chronic beta adrenergic receptor stimulation induced cardiomyopathy was rescued by AC5 KO. Conversely, in AC5 transgenic (Tg) mice, where AC5 is overexpressed in the heart, the cardiomyopathy was exacerbated and was rescued by enhancing oxidative stress resistance. Thus, the AC5 KO model, which resists oxidative stress, is uniquely designed for clinical translation, since it not only increases longevity and exercise, but also protects against diabetes, obesity, and cardiomyopathy. Importantly, inhibition of AC5's action to prolong longevity and enhance healthful aging, as well as its mechanism through resistance to oxidative stress, is unique among all of the nine AC isoforms. PMID:25945149

  15. Oxidative stress is a mediator for increased lipid accumulation in a newly isolated Dunaliella salina strain.

    PubMed

    Yilancioglu, Kaan; Cokol, Murat; Pastirmaci, Inanc; Erman, Batu; Cetiner, Selim

    2014-01-01

    Green algae offer sustainable, clean and eco-friendly energy resource. However, production efficiency needs to be improved. Increasing cellular lipid levels by nitrogen depletion is one of the most studied strategies. Despite this, the underlying physiological and biochemical mechanisms of this response have not been well defined. Algae species adapted to hypersaline conditions can be cultivated in salty waters which are not useful for agriculture or consumption. Due to their inherent extreme cultivation conditions, use of hypersaline algae species is better suited for avoiding culture contamination issues. In this study, we identified a new halophilic Dunaliella salina strain by using 18S ribosomal RNA gene sequencing. We found that growth and biomass productivities of this strain were directly related to nitrogen levels, as the highest biomass concentration under 0.05 mM or 5 mM nitrogen regimes were 495 mg/l and 1409 mg/l, respectively. We also confirmed that nitrogen limitation increased cellular lipid content up to 35% under 0.05 mM nitrogen concentration. In order to gain insight into the mechanisms of this phenomenon, we applied fluorometric, flow cytometric and spectrophotometric methods to measure oxidative stress and enzymatic defence mechanisms. Under nitrogen depleted cultivation conditions, we observed increased lipid peroxidation by measuring an important oxidative stress marker, malondialdehyde and enhanced activation of catalase, ascorbate peroxidase and superoxide dismutase antioxidant enzymes. These observations indicated that oxidative stress is accompanied by increased lipid content in the green alga. In addition, we also showed that at optimum cultivation conditions, inducing oxidative stress by application of exogenous H2O2 leads to increased cellular lipid content up to 44% when compared with non-treated control groups. Our results support that oxidative stress and lipid overproduction are linked. Importantly, these results also suggest that

  16. Accelerated tissue aging and increased oxidative stress in broiler chickens fed allopurinol.

    PubMed

    Klandorf, H; Rathore, D S; Iqbal, M; Shi, X; Van Dyke, K

    2001-06-01

    Uric acid has been hypothesized as being one of the more important antioxidants in limiting the accumulation of glycosylated endproducts in birds. Study 1 was designed to quantitatively manipulate the plasma concentrations of uric acid using hemin and allopurinol while study 2 determined their effects on skin pentosidine, the shear force value of Pectoralis major muscle, plasma glucose, body weight and chemiluminescence monitored oxidative stress in broiler chickens. Hemin was hypothesized to raise uric acid concentrations thereby lowering oxidative stress whereas allopurinol was hypothesized to lower uric acid concentrations and raise measures of oxidative stress. In study 1 feeding allopurinol (10 mg/kg body weight) to 8-week-old broiler chicks (n=50) for 10 days decreased plasma uric acid by 57%. However, hemin (10 mg/kg body weight) increased uric acid concentrations 20%. In study 2, 12-week-old broiler chicks (n=90) were randomly assigned to either an ad libitum (AL) diet or a diet restricted (DR) group. Each group was further divided into three treatments (control, allopurinol or hemin fed). Unexpectedly, hemin did not significantly effect uric acid concentrations but increased (P<0.05) measures of chemiluminescence dependent oxidative stress in both the DR and AL birds probably due to the ability of iron to generate oxygen radicals. Allopurinol lowered concentrations of uric acid and increased (P<0.05) the oxidative stress in the AL birds at week 22, reduced (P<0.05) body weight in both the AL and DR fed birds at 16 and 22 weeks of age, and markedly increased (P<0.001) shear force values of the pectoralis major muscle. Skin pentosidine levels increased (P<0.05) in AL birds fed allopurinol or hemin fed birds, but not in the diet restricted birds at 22 weeks. The significance of these studies is that concentrations of plasma uric acid can be related to measures of oxidative stress, which can be linked to tissue aging.

  17. Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake

    PubMed Central

    Dhanya, R.; Arun, K. B.; Nisha, V. M.; Syama, H. P.; Nisha, P.; Santhosh Kumar, T. R.; Jayamurthy, P.

    2015-01-01

    Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH) & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 μM) showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2 - NBDG) on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS) production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control. PMID:26147673

  18. Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake.

    PubMed

    Dhanya, R; Arun, K B; Nisha, V M; Syama, H P; Nisha, P; Santhosh Kumar, T R; Jayamurthy, P

    2015-01-01

    Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH) & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 μM) showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS) production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control.

  19. Increase in antioxidant gene transcripts, stress tolerance and biocontrol efficacy of Candida oleophila following sublethal oxidative stress exposure.

    PubMed

    Liu, Jia; Wisniewski, Michael; Droby, Samir; Norelli, John; Hershkovitz, Vera; Tian, Shiping; Farrell, Robert

    2012-06-01

    A pretreatment of the yeast, Candida oleophila, with 5 mM H(2)O(2) for 30 min (sublethal) increased yeast tolerance to subsequent lethal levels of oxidative stress (50 mM H(2)O(2)), high temperature (40 °C), and low pH (pH 4). Compared with non-stress-adapted yeast cells, stress-adapted cells exhibited better control of apple fruit infections by Penicillium expansum and Botrytis cinerea and had initially higher growth rates in apple wounds. Suppression subtractive hybridization analysis was used to identify genes expressed in yeast in response to sublethal oxidative stress. Transcript levels were confirmed using semiquantitative reverse transcription-PCR. Seven antioxidant genes were upregulated. The elevated expression of these genes was associated with less accumulation of reactive oxygen species and a lower level of protein and lipid oxidation under subsequent stresses. These data support the premise that induction of abiotic stress tolerance in biocontrol yeast can improve biocontrol efficacy by upregulation of genes involved in the amelioration of oxidative stress. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  20. Increased Oxidative Stress in Cultured 3T3-L1 Cells was Attenuated by Berberine Treatment.

    PubMed

    Dong, Shi-Fen; Yasui, Naomi; Negishb, Hiroko; Kishimoto, Aya; Sun, Jian-Ning; Ikeda, Katsumi

    2015-06-01

    The 3T3-L1 cell line is one of the most well-characterized and reliable models for studying adipocytes. Increased oxidative stress in accumulated fat was found in 3T3-L1 cells. Berberine, an isoquinoline alkaloid, could suppress fat deposition in 3T3-L1 cells; however, whether berberine suppresses increased oxidative stress is not well known. In this study, we observed the effect of berberine on increased oxidative stress in 3T3-L1 cells. 3T3-L1 cells were cultured and treated with berberine (5-20 μM) from day 3 to day 8. We confirmed that berberine markedly inhibited fat accumulation and lipid droplets in 3T3-L1 adipocytes and decreased triglyceride content. Berberine inhibited increased oxidative stress in 3T3-L1 cells by suppressing reactive oxygen species (ROS) production, and increased glutathione peroxidase (GPx) gene expression and GPx activity. Berberine also markedly reduced adipokines secreted by adipocytes, including leptin and resistin.

  1. Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress

    PubMed Central

    Naqvi, Saba; Samim, Mohammad; Abdin, MZ; Ahmed, Farhan Jalees; Maitra, AN; Prashant, CK; Dinda, Amit K

    2010-01-01

    Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774) cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15–30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in lower concentrations (25–200 μg/mL) and up to three hours of exposure, whereas at higher concentrations (300–500 μg/mL) and prolonged (six hours) exposure viability reduced to 55%–65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H2DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS) indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury induced by nanoparticles studied using the lactate dehydrogenase assay, showed both concentration- and time-dependent damage. Thus, this study concluded that use of a low optimum concentration of superparamagnetic iron oxide nanoparticles is important for avoidance of oxidative stress-induced cell injury and death. PMID:21187917

  2. Perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in non-human primates.

    PubMed

    Westbrook, David G; Anderson, Peter G; Pinkerton, Kent E; Ballinger, Scott W

    2010-09-01

    Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility. Similarly, molecular studies in mice have shown that in utero exposure to cardiovascular disease (CVD) risk factors such as environmental tobacco smoke (ETS) increased adult atherogenic susceptibility and mitochondrial damage; however, the molecular effects of similar exposures in primates are not yet known. To determine whether perinatal ETS exposure increased mitochondrial damage, dysfunction and oxidant stress in primates, archived tissues from the non-human primate model Macaca mulatta (M. mulatta) were utilized. M. mulatta were exposed to low levels of ETS (1 mg/m(3) total suspended particulates) from gestation (day 40) to early childhood (1 year), and aortic tissues were assessed for oxidized proteins (protein carbonyls), antioxidant activity (SOD), mitochondrial function (cytochrome oxidase), and mitochondrial damage (mitochondrial DNA damage). Results revealed that perinatal ETS exposure resulted in significantly increased oxidative stress, mitochondrial dysfunction and damage which were accompanied by significantly decreased mitochondrial antioxidant capacity and mitochondrial copy number in vascular tissue. Increased mitochondrial damage was also detected in buffy coat tissues in exposed M. mulatta. These studies suggest that perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in primates, potentially increasing adult disease susceptibility.

  3. Aluminium sulphate exposure increases oxidative stress and suppresses brain development in Ross broiler chicks

    PubMed Central

    Oğuz, Emin Oğuzhan; Enli, Yaşar; Şahin, Barbaros; Gönen, Cafer; Turgut, Günfer

    2012-01-01

    Summary Background Aluminium (Al) is known to have neurotoxic effects that can result in oxidative damage to a range of cellular biomolecules. These effects appear to be of significance in the developmental stages of the brain. We therefore investigated the oxidative and histopathological damage induced by Al during growth and development of the chick brain. Material/Methods We used a chick embryonic development model, with Al treatment of 500 μg Al sulphate in 0.1 ml saline injected into the egg air chambers at the beginning of their incubation period. The effects on chick-brain growth and development were then assessed at term (day 21). Determination of malondialdehyde and glutathione levels were used as relevant biological measures for increased oxidative stress in terms of lipid peroxidation and biochemical oxidative damage, respectively. Furthermore, we also monitored neuronal degeneration as estimated stereologically using the Cavalieri brain volume estimation tool. Results This Al treatment showed significantly increased MDA levels and decreased GSH levels, as indicators of increased biochemical oxidative damage. This was accompanied by significantly decreased brain volume, as a measure of neuronal degeneration during brain development in this chick embryonic development model. Conclusions Exposure to Al during chick embryonic development results in increased oxidative stress in the brain that is accompanied by neuronal degeneration. PMID:22367119

  4. Increasing Fatty Acid Oxidation Remodels the Hypothalamic Neurometabolome to Mitigate Stress and Inflammation

    PubMed Central

    McFadden, Joseph W.; Aja, Susan; Li, Qun; Bandaru, Veera V. R.; Kim, Eun-Kyoung; Haughey, Norman J.; Kuhajda, Francis P.; Ronnett, Gabriele V.

    2014-01-01

    Modification of hypothalamic fatty acid (FA) metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO) from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1) and fatty acid oxidation (FAOx), exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT) inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK) in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS), and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism. PMID:25541737

  5. Low ascorbic acid and increased oxidative stress in gulo−/− mice during development

    PubMed Central

    Harrison, Fiona E.; Meredith, M. Elizabeth; Dawes, Sean M.; Saskowski, Jeanette L.; May, James M.

    2010-01-01

    Vitamin C (ascorbic acid, AA) depletion during pre-natal and post-natal development can lead to oxidative stress in the developing brains and other organs. Such damage may lead to irreversible effects on later brain function. We studied the relationship between AA deficiency and oxidative stress during development in gulonolactone oxidase (gulo) knockout mice that are unable to synthesize their own ascorbic acid. Heterozygous gulo(+/−) mice can synthesize AA and typically have similar tissue levels to wild-type mice. Gulo(+/−) dams were mated with gulo(+/−) males to provide offspring of each possible genotype. Overall, embryonic day 20 (E20) and post-natal day 1 (P1) pups were protected against oxidative stress by sufficient AA transfer during pregnancy. On post-natal day 10 (P10) AA levels were dramatically lower in liver and cerebellum in gulo (−/−) mice and malondialdehyde (MDA) levels were significantly increased. In post-natal day 18 pups (P18) AA levels decreased further in gulo(−/−) mice and oxidative stress was observed in the accompanying elevations in MDA in liver, and F2-isoprostanes in cortex. Further, total glutathione levels were higher in gulo(−/−) mice in cortex, cerebellum and liver, indicating that a compensatory antioxidant system was activated. These data show a direct relationship between AA level and oxidative stress in the gulo(−/−) mice. They reinforce the critical role of ascorbic acid in preventing oxidative stress in the developing brain in animals that, like humans, cannot synthesize their own AA. PMID:20599829

  6. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

    PubMed

    Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

    2015-06-15

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

  7. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  8. Increased oxidative stress and apoptosis in peripheral blood mononuclear cells of fructose-fed rats.

    PubMed

    Porto, Marcella L; Lírio, Layla M; Dias, Ananda T; Batista, Alan T; Campagnaro, Bianca P; Mill, José G; Meyrelles, Silvana S; Baldo, Marcelo P

    2015-12-01

    Measuring of oxidative stress in peripheral blood mononuclear cells is a suitable model of dietary induced systemic oxidative stress. Thus, we aimed to evaluate whether a chronic high fructose intake could induce oxidative damage in peripheral blood and bone marrow mononuclear cells of rats. Animals were randomly assigned to the following groups: Control group (standard rat chow and tap water n=8), and Fructose group (standard rat chow and a 10% fructose solution in the drinking water n=8). Reactive oxygen species and cytokines were measure using flow cytometry in peripheral blood and bone-marrow mononuclear cells. Apoptotic cell death and the advanced oxidation protein products (AOPP) were also determined. We observed a significant increase in ROS production in peripheral blood mononuclear cells of fructose group as compared to control rats. Apoptosis and the AOPP were higher in those animals underwent high fructose intake. Serum levels of IL-6 and IL-12 were also increased after 12 weeks of high fructose intake. We concluded that fructose intake leads to systemic oxidative stress and pro-inflammatory condition which affect peripheral blood mononuclear cells and bone-marrow mononuclear cells viability. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Oxidative stress conditions increase the frequency of de novo formation of the yeast [PSI +] prion

    PubMed Central

    Doronina, Victoria A.; Staniforth, Gemma L.; Speldewinde, Shaun H.; Tuite, Mick F.

    2015-01-01

    Summary Prions are self‐perpetuating amyloid protein aggregates which underlie various neurodegenerative diseases in mammals and heritable traits in yeast. The molecular basis of how yeast and mammalian prions form spontaneously into infectious amyloid‐like structures is poorly understood. We have explored the hypothesis that oxidative stress is a general trigger for prion formation using the yeast [PSI +] prion, which is the altered conformation of the Sup35 translation termination factor. We show that the frequency of [PSI +] prion formation is elevated under conditions of oxidative stress and in mutants lacking key antioxidants. We detect increased oxidation of Sup35 methionine residues in antioxidant mutants and show that overexpression of methionine sulphoxide reductase abrogates both the oxidation of Sup35 and its conversion to the [PSI +] prion. [PSI +] prion formation is particularly elevated in a mutant lacking the Sod1 Cu,Zn‐superoxide dismutase. We have used fluorescence microscopy to show that the de novo appearance of [PSI +] is both rapid and increased in frequency in this mutant. Finally, electron microscopy analysis of native Sup35 reveals that similar fibrillar structures are formed in both the wild‐type and antioxidant mutants. Together, our data indicate that oxidative stress is a general trigger of [PSI +] formation, which can be alleviated by antioxidant defenses. PMID:25601439

  10. Acute exercise increases resistance to oxidative stress in young but not older adults.

    PubMed

    Nordin, Trevor C; Done, Aaron J; Traustadóttir, Tinna

    2014-01-01

    A single bout of acute exercise increases oxidative stress and stimulates a transient increase in antioxidant enzymes. We asked whether this response would induce protection from a subsequent oxidative challenge, different from that of exercise, and whether the effects were affected by aging. We compared young (20 ± 1 years, n = 8) and older (58 ± 6 years, n = 9) healthy men and women. Resistance to oxidative stress was measured by the F2-isoprostane response to forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial twice, in random order; once after performing 45 min of cycling on the preceding day (IRX) and a control trial without any physical activity (IRC). Baseline F2-isoprostane levels were significantly lower at IRX compared to IRC (P < 0.05) and not different between groups. F2-isoprostane response to IRX was significantly lower compared to IRC in young (P < 0.05) but not different in the older group. Superoxide dismutase activity in response to acute exercise was significantly higher in young compared to older adults (P < 0.05). These data suggest that signal transduction of acute exercise may be impaired with aging. Repeated bouts of transient reactive oxygen species production as seen with regular exercise may be needed to increase resistance to oxidative stress in older individuals.

  11. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

    USDA-ARS?s Scientific Manuscript database

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

  12. Moderate Weight Loss Decreases Oxidative Stress and Increases Antioxidant Status in Patients with Metabolic Syndrome

    PubMed Central

    Del Ben, Maria; Angelico, Francesco; Cangemi, Roberto; Loffredo, Lorenzo; Carnevale, Roberto; Augelletti, Teresa; Baratta, Francesco; Polimeni, Licia; Pignatelli, Pasquale; Violi, Francesco

    2012-01-01

    Background. Oxidative stress is enhanced in metabolic syndrome (MetS) and believed to contribute to accelerated atherosclerosis. Weight loss is associated with lowered oxidative stress. Methods. We performed a cross-sectional study in 92 consecutive patients with metabolic syndrome and 80 without. A dietary intervention with moderately low-calorie diet (600 calories/day negative energy balance) was carried out in 53 of metabolic syndrome patients. Oxidative stress, assessed by sNOX2-dp and urinary 8-iso-PGF2α, and antioxidant status, assessed by serum levels of vitamin E and adiponectin, were measured before and after 6 months. Results. Serum vitamin E/cholesterol ratio was significantly lower in metabolic syndrome compared to controls (P < 0.001) and decreased by increasing the number of metabolic syndrome components (P < 0.001). After six months, 23 and 30 patients showed >5% (group A) or <5% (group B) weight loss, respectively. Urinary 8-iso-PGF2α (−39.0%), serum sNOX2-dp (−22.2%), adiponectin (+125%), and vitamin E/cholesterol ratio (+129.8%) significantly changed only in A group. Changes in body weight and in serum adiponectin were independent predictors of vitamin E/cholesterol ratio variation. Conclusion. Our findings show that in metabolic syndrome moderate weight loss is associated with multiple health benefits including not only oxidative stress reduction but also enhancement of antioxidant status. PMID:24533215

  13. Increase in oxidative stress biomarkers in dogs with ascending-descending myelomalacia following spinal cord injury.

    PubMed

    Marquis, Andrew; Packer, Rebecca A; Borgens, Richard B; Duerstock, Bradley S

    2015-01-01

    Multiple biochemical and immunohistochemical tests were performed to elucidate the role of oxidative stress during ascending-descending (A-D) myelomalacia by comparing dogs with this progressive terminal condition to dogs with chronic, focal spinal cord injuries (SCIs) and controls without SCI. Dogs with A-D myelomalacia exhibited increased biochemical markers for oxidative stress, including 8-isoprostane F2α and acrolein, as well as decreased endogenous glutathione with greatest changes occurring at the lesion center. Inflammation, as evident by the concentration of CD18+ phagocytes and hemorrhagic necrosis, was also exacerbated in the lesion of A-D myelomalacic spinal cord compared to focal SCI. The greatest differences in oxidative stress occurred at the lesion center and diminished distally in both spinal cords with A-D myelomalacia and focal SCIs. The spatial progression and time course of A-D myelomalacia are consistent with the development of secondary injury post-SCI. Ascending-descending myelomalacia is proposed as a clinical model that may further the understanding of the role of oxidative stress during secondary injury. Our results indicate that the pathology of A-D myelomalacia is also similar to subacute progressive ascending myelopathy in humans, which is characterized by recurrent neurodegeneration of spinal cord post-injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Oxidative Stress in Hypertensive Patients Induces an Increased Contractility in Vein Grafts Independent of Endothelial Function

    PubMed Central

    Joo Turoni, Claudio; Marañón, Rodrigo; Karbiner, Maria; Muntaner, Juan; Proto, Víctor; Peral de Bruno, María

    2011-01-01

    Objective. To evaluate the impact of oxidative stress on vascular reactivity to vasoconstrictors and on nitric oxide (NO) bioavailability in saphenous vein (SV) graft with endothelial dysfunction from hypertensive patients (HT). Methods. Endothelial function, vascular reactivity, oxidative state, nitrites and NO release were studied in isolated SV rings from HT and normotensive patients (NT). Only rings with endothelial dysfunction were used. Results. HT rings presented a hyperreactivity to vasoconstrictors that was reverted by diphenylene iodonium (DPI). In NT, no effect of DPI was obtained, but Nω-nitro-L-arginine methyl ester (L-NAME) increased the contractile response. NO was present in SV rings without endothelial function. Nitrites were higher in NT than in HT (1066.1 ± 86.3 pmol/mg; n = 11 versus 487.8 ± 51.6; n = 23; P < 0.01) and inhibited by nNOS inhibitor. L-arginine reversed this effect. Antioxidant agents increased nitrites and NO contents only in HT. The anti-nNOS-stained area by immunohistochemistry was higher in NT than HT. HT showed an elevation of oxidative state. Conclusions. Extraendothelial NO counter-regulates contractility in SV. However, this action could be altered in hypertensive situations by an increased oxidative stress or a decreased ability of nNOS to produce NO. Further studies should be performed to evaluate the implication of these results in graft patency rates. PMID:22164326

  15. IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease.

    PubMed

    Sadagurski, Marianna; Cheng, Zhiyong; Rozzo, Aldo; Palazzolo, Isabella; Kelley, Gregory R; Dong, Xiaocheng; Krainc, Dimitri; White, Morris F

    2011-10-01

    Aging is a major risk factor for the progression of neurodegenerative diseases, including Huntington disease (HD). Reduced neuronal IGF1 or Irs2 signaling have been shown to extend life span in mice. To determine whether Irs2 signaling modulates neurodegeneration in HD, we genetically modulated Irs2 concentrations in the R6/2 mouse model of HD. Increasing Irs2 levels in the brains of R6/2 mice significantly reduced life span and increased neuronal oxidative stress and mitochondrial dysfunction. In contrast, reducing Irs2 levels throughout the body (except in β cells, where Irs2 expression is needed to prevent diabetes onset; R6/2•Irs2+/-•Irs2βtg mice) improved motor performance and extended life span. The slower progression of HD-like symptoms was associated with increased nuclear localization of the transcription factor FoxO1 and increased expression of FoxO1-dependent genes that promote autophagy, mitochondrial function, and resistance to oxidative stress. Mitochondrial function improved and the number of autophagosomes increased in R6/2•Irs2+/-•Irs2βtg mice, whereas aggregate formation and oxidative stress decreased. Thus, our study suggests that Irs2 signaling can modulate HD progression. Since we found the expression of Irs2 to be normal in grade II HD patients, our results suggest that decreasing IRS2 signaling could be part of a therapeutic approach to slow the progression of HD.

  16. Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation.

    PubMed

    Petrick, Lauren; Rosenblat, Mira; Paland, Nicole; Aviram, Michael

    2016-06-01

    Nanoparticle research has focused on their toxicity in general, while increasing evidence points to additional specific adverse effects on atherosclerosis development. Arterial macrophage cholesterol and triglyceride (TG) accumulation and foam cell formation are the hallmark of early atherogenesis, leading to cardiovascular events. To investigate the in vitro atherogenic effects of silicon dioxide (SiO2 ), J774.1 cultured macrophages (murine cell line) were incubated with SiO2 nanoparticle (SP, d = 12 nm, 0-20 µg/mL), followed by cellular cytotoxicity, oxidative stress, TG and cholesterol metabolism analyses. A significant dose-dependent increase in oxidative stress (up to 164%), in cytotoxicity (up to 390% measured by lactate dehydrogenase (LDH) release), and in TG content (up to 63%) was observed in SiO2 exposed macrophages compared with control cells. A smaller increase in macrophage cholesterol mass (up to 22%) was noted. TG accumulation in macrophages was not due to a decrease in TG cell secretion or to an increased TG biosynthesis rate, but was the result of attenuated TG hydrolysis secondary to decreased lipase activity and both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein expression (by 42 and 25%, respectively). Overall, SPs showed pro-atherogenic effects on macrophages as observed by cytotoxicity, increased oxidative stress and TG accumulation. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 713-723, 2016. © 2014 Wiley Periodicals, Inc.

  17. Increased oxidative stress and antioxidant expression in mouse keratinocytes following exposure to paraquat

    SciTech Connect

    Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.; Laskin, Debra L. Heck, Diane E.; Laskin, Jeffrey D.

    2008-09-15

    Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which was greater in differentiated cells. Paraquat treatment also resulted in increased expression of HO-1, Cu,Zn-SOD, catalase, GSTP1, GSTA3 and GSTA4. However, no major differences in expression of these enzymes were evident between undifferentiated and differentiated cells. In contrast, expression of GSTA1-2 was significantly greater in differentiated relative to undifferentiated cells after paraquat treatment. No changes in expression of MT-2, Mn-SOD, GPx-1, GSTM1 or the microsomal GST's mGST1, mGST2 and mGST3, were observed in response to paraquat. These data demonstrate that paraquat induces oxidative stress in keratinocytes leading to increased expression of antioxidant genes. These intracellular proteins may be important in protecting the skin from paraquat-mediated cytotoxicity.

  18. Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels

    SciTech Connect

    Dutta, Anindita; Ray, Manas Ranjan; Banerjee, Anirban

    2012-06-15

    The study was undertaken to investigate whether regular cooking with biomass aggravates systemic inflammation and oxidative stress that might result in increase in the risk of developing cardiovascular disease (CVD) in rural Indian women compared to cooking with a cleaner fuel like liquefied petroleum gas (LPG). A total of 635 women (median age 36 years) who cooked with biomass and 452 age-matched control women who cooked with LPG were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by ELISA. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. Tachycardia was determined as pulse rate > 100 beats per minute. Particulate matter of diameter less than 10 and 2.5 μm (PM{sub 10} and PM{sub 2.5}, respectively) in cooking areas was measured using real-time aerosol monitor. Compared with control, biomass users had more particulate pollution in indoor air, their serum contained significantly elevated levels of IL-6, IL-8, TNF-α and CRP, and ROS generation was increased by 37% while SOD was depleted by 41.5%, greater prevalence of hypertension and tachycardia compared to their LPG-using neighbors. PM{sub 10} and PM{sub 2.5} levels were positively associated with markers of inflammation, oxidative stress and hypertension. Inflammatory markers correlated with raised blood pressure. Cooking with biomass exacerbates systemic inflammation, oxidative stress, hypertension and tachycardia in poor women cooking with biomass fuel and hence, predisposes them to increased risk of CVD development compared to the controls. Systemic inflammation and oxidative stress may be the mechanistic factors involved in the development of CVD. -- Highlights: ► Effect of chronic biomass smoke exposure on

  19. Cardiogel supports adhesion, proliferation and differentiation of stem cells with increased oxidative stress protection.

    PubMed

    Sreejit, P; Verma, R S

    2011-01-25

    Cultured murine bone marrow derived mesenchymal stem cells (BMSC) when grown along with cardiogel derived from mouse cardiac fibroblast, exhibited increased cell proliferation and differentiation and enhanced survival under oxidative stress induced by the exposure of H2O2 in vitro (similar to in vivo ischemia like condition). Adhesion of BMSC to the cardiogel occurred at a faster rate when compared to the cells grown on normal surface. BMSC attached to cardiogel showed an increased resistance to proteolytic (enzymatic) disassociation. This is the first report on an attempt to use an in house biomaterial for the growth of BMSC that led to their heightened resistance towards oxidative stress. These studies support that cardiogel is an efficient biodegradable three-dimensional extracellular matrix which supports better growth of BMSC and can be used as a scaffold for stem cell delivery, with potential therapeutic applications in cardiac tissue regeneration.

  20. Different sub-anesthetic doses of ketamine increase oxidative stress in the brain of rats.

    PubMed

    de Oliveira, Larissa; Spiazzi, Cecília Marly dos S; Bortolin, Thaize; Canever, Leila; Petronilho, Fabricia; Mina, Franciele Gonçalves; Dal-Pizzol, Felipe; Quevedo, João; Zugno, Alexandra I

    2009-08-31

    Schizophrenia is a complex neuropsychiatric disorder in which symptoms can be classified as either positive, such as delusions and hallucinations, or negative, such as blunted affect and social withdrawal. However, the mechanisms underlying this disease are poorly understood. There is evidence that reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. Ketamine has been used to induce a schizophrenia-like condition as an animal model in which to study this condition. In the present study we tested the effects of sub-anesthetic doses of ketamine on various parameters of oxidative stress in the brain of rats. Our results indicate that lipid peroxidation and tissue protein oxidation were affected by varying sub-anesthetic doses of ketamine in multiple cerebral structures. Additionally, the activity of the antioxidant enzymes CAT and SOD was measured and was also found to be altered in most of the structures tested. In conclusion, we observe an increase in oxidative damage marked by an increase in lipid peroxidation, oxidative protein damage and a decrease in enzymatic defenses, in an animal model of schizophrenia. Given that oxidative stress could be related to schizophrenia, these findings may explain, at least in part, the mechanisms underlying in this disease.

  1. Ultraviolet radiation does not increase oxidative stress in the lizard Psammodromus algirus along an elevational gradient.

    PubMed

    Reguera, Senda; Zamora-Camacho, Francisco J; Melero, Elena; García-Mesa, Sergio; Trenzado, Cristina E; Cabrerizo, Marco J; Sanz, Ana; Moreno-Rueda, Gregorio

    2015-05-01

    Lizards, as ectotherms, spend much time basking for thermoregulating exposed to solar radiation. Consequently, they are subjected to ultraviolet radiation (UVR), which is the most harmful component of solar radiation spectrum. UVR can provoke damages, from the molecular to tissue level, even cause death. Photooxidation triggered by UVR produces reactive oxidative species (ROS). When antioxidant machinery cannot combat the ROS concentration, oxidative stress occurs in the organisms. Given that UVR increases with elevation, we hypothesised that lizards from high elevations should be better adapted against UVR than lizards from lower elevations. In this work, we test this hypothesis in Psammodromus algirus along an elevation gradient (three elevational belts, from 300 to 2500 m above sea level). We ran an experiment in which lizards from each elevation belt were exposed to 5-hour doses of UVR (UV-light bulb, experimental group) or photosynthetically active radiation (white-light bulb, control group) and, 24 h after the exposure, we took tissue samples from the tail. We measured oxidative damage (lipid and protein peroxidation) and antioxidant capacity as oxidative-stress biomarkers. We found no differences in oxidative stress between treatments. However, consistent with a previous work, less oxidative damage appeared in lizards from the highlands. We conclude that UVR is not a stressor agent for P. algirus; however, our findings suggest that the lowland environment is more oxidative for lizards. Therefore, P. algirus is well adapted to inhabit a large elevation range, and this would favour the lizard in case it ascends in response to global climate change. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress.

    PubMed

    Bonilha, Vera L; Bell, Brent A; Rayborn, Mary E; Samuels, Ivy S; King, Anna; Hollyfield, Joe G; Xie, Chengsong; Cai, Huaibin

    2017-03-01

    Oxidative stress alters physiological function in most biological tissues and can lead to cell death. In the retina, oxidative stress initiates a cascade of events leading to focal loss of RPE and photoreceptors, which is thought to be a major contributing factor to geographic atrophy. Despite these implications, the molecular regulation of RPE oxidative stress under normal and pathological conditions remains largely unknown. A better understanding of the mechanisms involved in regulating RPE and photoreceptors oxidative stress response is greatly needed. To this end we evaluated photoreceptor and RPE changes in mice deficient in DJ-1, a protein that is thought to be important in protecting cells from oxidative stress. Young (3 months) and aged (18 months) DJ-1 knockout (DJ-1 KO) and age-matched wild-type mice were examined. In both group of aged mice, scanning laser ophthalmoscopy (SLO) showed the presence of a few autofluorescent foci. The 18 month-old DJ-1 KO retinas were also characterized by a noticeable increase in RPE fluorescence to wild-type. Optical coherence tomography (OCT) imaging demonstrated that all retinal layers were present in the eyes of both DJ-1 KO groups. ERG comparisons showed that older DJ-1 KO mice had reduced sensitivity under dark- and light-adapted conditions compared to age-matched control. Histologically, the RPE contained prominent vacuoles in young DJ-1 KO group with the appearance of enlarged irregularly shaped RPE cells in the older group. These were also evident in OCT and in whole mount RPE/choroid preparations labeled with phalloidin. Photoreceptors in the older DJ-1 KO mice displayed decreased immunoreactivity to rhodopsin and localized reduction in cone markers compared to the wild-type control group. Lower levels of activated Nrf2 were evident in retina/RPE lysates in both young and old DJ-1 KO mouse groups compared to wild-type control levels. Conversely, higher levels of protein carbonyl derivatives and i

  3. Persistent oxidative stress following renal ischemia-reperfusion injury increases ANG II hemodynamic and fibrotic activity

    PubMed Central

    Leonard, Ellen C.; Beal, Alisa G.; Schleuter, Devin; Friedrich, Jessica

    2012-01-01

    ANG II is a potent renal vasoconstrictor and profibrotic factor and its activity is enhanced by oxidative stress. We sought to determine whether renal oxidative stress was persistent following recovery from acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) injury in rats and whether this resulted in increased ANG II sensitivity. Rats were allowed to recover from bilateral renal I/R injury for 5 wk and renal blood flow responses were measured. Post-AKI rats showed significantly enhanced renal vasoconstrictor responses to ANG II relative to sham-operated controls and treatment of AKI rats with apocynin (15 mM, in the drinking water) normalized these responses. Recovery from AKI for 5 wk resulted in sustained oxidant stress as indicated by increased dihydroethidium incorporation in renal tissue slices and was normalized in apocynin-treated rats. Surprisingly, the renal mRNA expression for common NADPH oxidase subunits was not altered in kidneys following recovery from AKI; however, mRNA screening using PCR arrays suggested that post-AKI rats had decreased renal Gpx3 mRNA and an increased expression other prooxidant genes such as lactoperoxidase, myeloperoxidase, and dual oxidase-1. When rats were infused for 7 days with ANG II (100 ng·kg−1·min−1), renal fibrosis was not apparent in sham-operated control rats, but it was enhanced in post-AKI rats. The profibrotic response was significantly attenuated in rats treated with apocynin. These data suggest that there is sustained renal oxidant stress following recovery from AKI that alters both renal hemodynamic and fibrotic responses to ANG II, and may contribute to the transition to chronic kidney disease following AKI. PMID:22442209

  4. Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels.

    PubMed

    Dutta, Anindita; Ray, Manas Ranjan; Banerjee, Anirban

    2012-06-15

    The study was undertaken to investigate whether regular cooking with biomass aggravates systemic inflammation and oxidative stress that might result in increase in the risk of developing cardiovascular disease (CVD) in rural Indian women compared to cooking with a cleaner fuel like liquefied petroleum gas (LPG). A total of 635 women (median age 36 years) who cooked with biomass and 452 age-matched control women who cooked with LPG were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by ELISA. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. Tachycardia was determined as pulse rate >100 beats per minute. Particulate matter of diameter less than 10 and 2.5 μm (PM₁₀ and PM₂.₅, respectively) in cooking areas was measured using real-time aerosol monitor. Compared with control, biomass users had more particulate pollution in indoor air, their serum contained significantly elevated levels of IL-6, IL-8, TNF-α and CRP, and ROS generation was increased by 37% while SOD was depleted by 41.5%, greater prevalence of hypertension and tachycardia compared to their LPG-using neighbors. PM₁₀ and PM₂.₅ levels were positively associated with markers of inflammation, oxidative stress and hypertension. Inflammatory markers correlated with raised blood pressure. Cooking with biomass exacerbates systemic inflammation, oxidative stress, hypertension and tachycardia in poor women cooking with biomass fuel and hence, predisposes them to increased risk of CVD development compared to the controls. Systemic inflammation and oxidative stress may be the mechanistic factors involved in the development of CVD.

  5. Increased salivary oxidative stress parameters in patients with type 2 diabetes: Relation with periodontal disease.

    PubMed

    Arana, Carlos; Moreno-Fernández, Ana María; Gómez-Moreno, Gerardo; Morales-Portillo, Cristóbal; Serrano-Olmedo, Isabel; de la Cuesta Mayor, M Carmen; Martín Hernández, Tomás

    2017-05-01

    The aim of this study was to determine whether there are differences in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2) and healthy non-diabetic patients, and whether this oxidative stress is associated with the presence of periodontal disease in diabetic patients. This observational study included 70 patients divided into three groups according to metabolic control levels: 19 non-diabetic patients (control group); 24 patients with good metabolic control (HbA1c<7%), and 27 patients DM2 with poor metabolic control (HbA1c>7%). The following oxidative stress parameters were measured in all subjects: glutathione peroxidase (GPx), glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione (GSSG). Periodontal health was determined by means of the community periodontal index (CPI) recommended by the WHO. The diabetic group with good metabolic control showed a significant increase in GPx and GRd activity in comparison with the control group (P<.001). The activity of the enzymes measured was significantly less in patients with poor metabolic control in comparison with the control group and well-controlled diabetic groups (P<.001). Both diabetic groups showed higher GSSG/GSH quotients and CPI in comparison with the control group, and both parameters were significantly higher in diabetic patients with poor metabolic control in comparison with well-controlled diabetic patients. Poor metabolic control in DM2 patients is associated with higher levels of salivary oxidative stress and worse periodontal health. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae.

    PubMed

    Bayliak, Maria; Burdyliuk, Nadia; Lushchak, Volodymyr

    2017-01-01

    Alpha-ketoglutarate (AKG) is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe(2+) and Cu(2+)) but not to ethanol and heat stress as compared with control ones. Deficiency in SODs or catalases abolished stress-protective effects of AKG. AKG-supplemented growth led to higher values of total metabolic activity, level of low-molecular mass thiols, and activities of catalase and glutathione reductase in wild-type cells compared with the control. The results suggest that exogenous AKG may enhance cell metabolism leading to induction of mild oxidative stress. It turn, it results in activation of antioxidant system that increases resistance of S. cerevisiae cells to H2O2 and other stresses. The presence of genes encoding SODs or catalases is required for the expression of protective effects of AKG.

  7. Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae

    PubMed Central

    Burdyliuk, Nadia; Lushchak, Volodymyr

    2017-01-01

    Alpha-ketoglutarate (AKG) is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe2+ and Cu2+) but not to ethanol and heat stress as compared with control ones. Deficiency in SODs or catalases abolished stress-protective effects of AKG. AKG-supplemented growth led to higher values of total metabolic activity, level of low-molecular mass thiols, and activities of catalase and glutathione reductase in wild-type cells compared with the control. The results suggest that exogenous AKG may enhance cell metabolism leading to induction of mild oxidative stress. It turn, it results in activation of antioxidant system that increases resistance of S. cerevisiae cells to H2O2 and other stresses. The presence of genes encoding SODs or catalases is required for the expression of protective effects of AKG. PMID:28154578

  8. Low Mercury Concentration Produces Vasoconstriction, Decreases Nitric Oxide Bioavailability and Increases Oxidative Stress in Rat Conductance Artery

    PubMed Central

    Ribeiro Junior, Rogério Faustino; Vassallo, Dalton Valentim; Padilha, Alessandra Simão; Stefanon, Ivanita

    2012-01-01

    Mercury is an environmental pollutant that reduces nitric oxide (NO) bioavailability and increases oxidative stress, having a close link with cardiovascular diseases, as carotid atherosclerosis, myocardial infarction, coronary heart disease and hypertension. One of the main sites affected by oxidative stress, which develops atherosclerosis, is the aorta. Under acute exposure to low mercury concentrations reactive oxygen species (ROS) production were only reported for resistance vessels but if low concentrations of mercury also affect conductance arteries it is still unclear. We investigated the acute effects of 6 nM HgCl2 on endothelial function of aortic rings measuring the reactivity to phenylephrine in rings incubated, or not, with HgCl2 for 45 min, the protein expression for cyclooxygenase 2 (COX-2) and the AT1 receptor. HgCl2 increased Rmax and pD2 to phenylephrine without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage abolished the increased reactivity to phenylephrine. The increase of Rmax and pD2 produced by L-NAME was smaller in the presence of HgCl2. Enalapril, losartan, indomethacin, furegrelate, the selective COX-2 inhibitor NS 398, superoxide dismutase and the NADPH oxidase inhibitor apocynin reverted HgCl2 effects on the reactivity to phenylephrine, COX-2 protein expression was increased, and AT1 expression reduced. At low concentration, below the reference values, HgCl2 increased vasoconstrictor activity by reducing NO bioavailability due to increased ROS production by NADPH oxidase activity. Results suggest that this is due to local release of angiotensin II and prostanoid vasoconstrictors. Results also suggest that acute low concentration mercury exposure, occurring time to time could induce vascular injury due to endothelial oxidative stress and contributing to increase peripheral resistance, being a high risk factor for public health. PMID:23145049

  9. Increased oxidative stress contributes to cardiomyocyte dysfunction and death in patients with Fabry disease cardiomyopathy.

    PubMed

    Chimenti, Cristina; Scopelliti, Fernanda; Vulpis, Elisabetta; Tafani, Marco; Villanova, Lidia; Verardo, Romina; De Paulis, Ruggero; Russo, Matteo A; Frustaci, Andrea

    2015-11-01

    Cardiac dysfunction of Fabry disease (FD) has been associated with myofilament damage and cell death as result of α-galactosidase A deficiency and globotriaosylceramide accumulation. We sought to evaluate the role of oxidative stress in FD cardiomyocyte dysfunction. Myocardial tissue from 18 patients with FD was investigated for the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine by immunohistochemistry. Western blot analysis for nitrotyrosine was also performed. Oxidative damage to DNA was investigated by immunostaining for 8-hydroxydeoxyguanosine (8-OHdG), whereas apoptosis was evaluated by in situ ligation with hairpin probes. iNOS and nitrotyrosine expression was increased in FD hearts compared with hypertrophic cardiomyopathy and normal controls. Remarkably, immunostaining was homogeneously expressed in FD male cardiomyocytes, whereas it was only detected in the affected cardiomyocytes of FD females. Western blot analysis confirmed an increase in FD cardiomyocyte protein nitration compared with controls. 8-OHdG was expressed in 25% of cardiomyocyte nuclei from FD patients, whereas it was absent in controls. The intensity of immunostaining for iNOS/nitrotyrosine correlated with 8-OHdG expression in cardiomyocyte nuclei. Apoptosis of FD cardiomyocytes was 187-fold higher than in controls, and apoptotic nuclei were positive for 8-OHdG. Cardiac dysfunction of FD reflects increased myocardial nitric oxide production with oxidative damage of cardiomyocyte myofilaments and DNA, causing cell dysfunction and death.

  10. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage.

    PubMed

    Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K; Tarpy, David R; Rueppell, Olav

    2016-10-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees.

  11. Increased oxidative stress in the placenta tissue and cell culture of tumour-bearing pregnant rats.

    PubMed

    Toledo, M T; Ventrucci, G; Gomes-Marcondes, M C C

    2011-11-01

    Placental dysfunction leads to foetal damage, which jeopardises the exchange between the maternal and foetal systems. We evaluated the effects of tumour growth on the activity of antioxidant enzymes and oxidative stress in placental tissue and cell culture from tumour-bearing pregnant rats compared to non-tumour-bearing pregnant rats that were ascitic fluid injected. Ascitic fluid is obtained from Walker tumour-bearing rats and contains a cytokine called Walker factor (WF), which is a molecule similar to proteolysis-inducing factor (PIF), and induces changes in protein metabolism and oxidative stress. Pregnant Wistar rats were distributed into control (C), tumour-bearing (W) and ascitic fluid injected (A) groups and were sacrificed on days 16, 19 and 21 of pregnancy to analyse the profile of enzyme activities (glutathione-S-transferase (GST), catalase (CAT), alkaline phosphatase (AP)) and malondialdehyde (MDA) content in placental tissue. Meanwhile, placenta samples from all groups were obtained on day 21, placed in primary culture and treated with WF for 72 h. The presence of tumour or ascitic fluid reduced the protein content of the placental tissue. On day 16 there was a significant reduction in AP activity in W rats, and on day 19, CAT activity and MDA content significantly increased. These results indicate that the presence of cancer decreased antioxidant enzyme capacity in the placenta, increasing the amount of oxidation in these cells, which may contribute to irreversible placental damage and compromisefoetal development. WF treatment induces similar changes in placental cells in primary culture, resulting in less cell viability and increased oxidative stress. These results indicate that WF, provided by the tumour or inoculation of ascitic fluid, has negative effects on placental homeostasis, which impairs foetal health.

  12. Dibutyltin promotes oxidative stress and increases inflammatory mediators in BV-2 microglia cells.

    PubMed

    Chantong, Boonrat; Kratschmar, Denise V; Lister, Adam; Odermatt, Alex

    2014-10-15

    The organotin dibutyltin (DBT) is used as biocide and as stabilizer in the manufacture of silicones, polyvinyl chloride plastics, polyurethanes and polyester systems. Although the immuno- and neurotoxicity of DBT has been recognized, the underlying mechanisms remained unclear and the impact of DBT on microglia cells has not yet been established. We now used cultured mouse BV-2 cells as a model of activated microglia to investigate the impact of DBT on oxidative stress and pro-inflammatory cytokines. DBT, at subcytotoxic concentrations, increased intracellular reactive oxygen species (ROS), mitochondrial mass, mitochondrial ROS, and the mRNA expression of inducible nitric oxide synthase (iNOS) and NADPH-dependent oxidase-2 (NOX-2). ATP levels were decreased by DBT, followed by activation of AMP-activated protein kinase (AMPK). Moreover, DBT potentiated the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Inhibition of NOX-2 diminished both ROS production and induction of IL-6 expression. The DBT-mediated increase in NF-κB activity and subsequent up regulation of IL-6 was abolished by co-treatment with a NF-κB inhibitor. Treatment of cells with pharmacological inhibitors indicated a role for mitogen-activated protein kinases (MAPKs), PI3K/Akt, protein kinase C (PKC) and phospholipase C (PLC) in the DBT-induced toxicity. Finally, the calcium chelator BAPTA-AM diminished oxidative stress and induction of IL-6 expression, indicating the involvement of increased intracellular calcium in the enhanced microglia activity upon exposure to DBT. Together, the results suggest that a potentiation of oxidative stress and pro-inflammatory cytokine expression in microglia cells contribute to the toxicity of DBT in the CNS.

  13. Iron chelators increase the resistance of Ataxia telangeictasia cells to oxidative stress.

    PubMed

    Shackelford, Rodney E; Manuszak, Ryan P; Johnson, Cybele D; Hellrung, Daniel J; Link, Charles J; Wang, Suming

    2004-10-05

    Ataxia telangeictasia (A-T) is an autosomal recessive disorder characterized by immune dysfunction, genomic instability, chronic oxidative damage, and increased cancer incidence. Previously, desferal was found to increase the resistance of A-T, but not normal cells to exogenous oxidative stress in the colony forming-efficiency assay, suggesting that iron metabolism is dysregulated in A-T. Since desferal both chelates iron and modulates gene expression, we tested the effects of apoferritin and the iron chelating flavonoid quercetin on A-T cell colony-forming ability. We demonstrate that apoferritin and quercetin increase the ability of A-T cells to form colonies. We also show that labile iron levels are significantly elevated in Atm-deficient mouse sera compared to syngeniec wild type mice. Our findings support a role for labile iron acting as a Fenton catalyst in A-T, contributing to the chronic oxidative stress seen in this disease. Our findings further suggest that iron chelators might promote the survival of A-T cells and hence, individuals with A-T.

  14. Increased resistance to oxidative stress in transgenic plants by targeting mannitol biosynthesis to chloroplasts

    SciTech Connect

    Shen, B.; Jensen, R.G.; Bohnert, H.J.

    1997-04-01

    To investigate the potential role of a polyol, mannitol, in oxidative stress protection, a bacterial mannitol-1-phosphate dehydrogenase gene was targeted to chloroplasts by the addition of an aminoterminal transit peptide. Transgenic tobacco (Nicotiana tabacum) lines accumulate mannitol at concentrations ranging from 2.5 to 7 {mu}mol/g fresh weight. Line BS1-31 accumulated approximately 100 mm mannitol in chloroplasts and was identical to the wild type in phenotype and photosynthetic performance. The presence of mannitol in chloroplasts resulted in an increased resistance to methyl viologen (MV)-induced oxidative stress, documented by the increased retention of chlorophyll in transgenic leaf tissue following MV treatment. In the presence of MV, isolated mesophyll cells of BS1-31 exhibited higher CO{sub 2} fixation than the wild type. When the hydroxyl radical probe dimethyl sulfoxide was introduced into cells, the initial formation rate of methane sulfinic acid was significantly lower in cells containing mannitol in the chloroplast compartment than in wild-type cells, indicating an increased hydroxyl radical-scavenging capacity in BS1-31 tobacco. We suggest that the chloroplast location of mannitol can supplement endogenous radical-scavenging mechanisms and reduce oxidative damage of cells by hydroxyl radicals. 43 refs., 5 figs., 1 tab.

  15. Deletion of afpab1 Causes Increased Sensitivity to Oxidative Stress and Hypovirulence in Aspergillus fumigatus

    PubMed Central

    Wang, Dongyang; Wang, Shunan; He, Dan; Gao, Song; Xue, Baiji; Wang, Li

    2016-01-01

    Aspergillus fumigatus AFPAB1 is the ortholog of the Aspergillus oryzae cytoplasmic messenger ribonucleoprotein granules AOPAB1 that function to depress the initiation of translation during stress. A. fumigatus can regulate its cellular physiology in response to environmental stresses, but there has been no research on Pab1 in A. fumigatus. The associated gene afpab1 was replaced with a hygromycin-selectable marker to generate the strain Δafpab1. Phenotypic analysis showed that the Δafpab1 grew more weakly than the wild-type strain. Also the germination rate of Δafpab1 was decreased when exposed to oxidative stress. The morphology of Δafpab1 spores also showed great changes. The killing rate of Δafpab1 by RAW264.7 murine macrophage cells was increased, and the reactive oxygen species (ROS) scavenging ability of Δafpab1 was decreased. Pathogenicity testing showed that the deletion strain had decreased virulence. Therefore, we conclude that afpab1 activity is correlated with susceptibility to oxidative stress, and deletion of afpab1 from A. fumigatus possibly leads to observed hypovirulence in an immunosuppressed mouse model. PMID:27801871

  16. Increased Reactive Oxygen Species Formation and Oxidative Stress in Rheumatoid Arthritis

    PubMed Central

    Mateen, Somaiya; Moin, Shagufta; Khan, Abdul Qayyum; Zafar, Atif; Fatima, Naureen

    2016-01-01

    Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder. Highly reactive oxygen free radicals are believed to be involved in the pathogenesis of the disease. In this study, RA patients were sub-grouped depending upon the presence or absence of rheumatoid factor, disease activity score and disease duration. RA Patients (120) and healthy controls (53) were evaluated for the oxidant—antioxidant status by monitoring ROS production, biomarkers of lipid peroxidation, protein oxidation and DNA damage. The level of various enzymatic and non-enzymatic antioxidants was also monitored. Correlation analysis was also performed for analysing the association between ROS and various other parameters. Methods Intracellular ROS formation, lipid peroxidation (MDA level), protein oxidation (carbonyl level and thiol level) and DNA damage were detected in the blood of RA patients. Antioxidant status was evaluated by FRAP assay, DPPH reduction assay and enzymatic (SOD, catalase, GST, GR) and non-enzymatic (vitamin C and GSH) antioxidants. Results RA patients showed a higher ROS production, increased lipid peroxidation, protein oxidation and DNA damage. A significant decline in the ferric reducing ability, DPPH radical quenching ability and the levels of antioxidants has also been observed. Significant correlation has been found between ROS and various other parameters studied. Conclusion RA patients showed a marked increase in ROS formation, lipid peroxidation, protein oxidation, DNA damage and decrease in the activity of antioxidant defence system leading to oxidative stress which may contribute to tissue damage and hence to the chronicity of the disease. PMID:27043143

  17. Consumption of Oxidized Soybean Oil Increased Intestinal Oxidative Stress and Affected Intestinal Immune Variables in Yellow-feathered Broilers.

    PubMed

    Liang, Fangfang; Jiang, Shouqun; Mo, Yi; Zhou, Guilian; Yang, Lin

    2015-08-01

    This study investigated the effect of oxidized soybean oil in the diet of young chickens on growth performance and intestinal oxidative stress, and indices of intestinal immune function. Corn-soybean-based diets containing 2% mixtures of fresh and oxidized soybean oil provided 6 levels (0.15, 1.01, 3.14, 4.95, 7.05, and 8.97 meqO2/kg) of peroxide value (POV) in the diets. Each dietary treatment, fed for 22 d, had 6 replicates, each containing 30 birds (n = 1,080). Increasing POV levels reduced average daily feed intake (ADFI) of the broilers during d 1 to 10, body weight and average daily gain at d 22 but did not affect overall ADFI. Concentrations of malondialdehyde (MDA) increased in plasma and jejunum as POV increased but total antioxidative capacity (T-AOC) declined in plasma and jejunum. Catalase (CAT) activity declined in plasma and jejunum as did plasma glutathione S-transferase (GST). Effects were apparent at POV exceeding 3.14 meqO2/kg for early ADFI and MDA in jejunum, and POV exceeding 1.01 meqO2/kg for CAT in plasma and jejunum, GST in plasma and T-AOC in jejunum. Relative jejunal abundance of nuclear factor kappa B (NF-κB) P50 and NF-κB P65 increased as dietary POV increased. Increasing POV levels reduced the jejunal concentrations of secretory immunoglobulin A and cluster of differentiation (CD) 4 and CD8 molecules with differences from controls apparent at dietary POV of 3.14 to 4.95 meqO2/kg. These findings indicated that growth performance, feed intake, and the local immune system of the small intestine were compromised by oxidative stress when young broilers were fed moderately oxidized soybean oil.

  18. High-fat feeding, but not strenuous exercise, increases blood oxidative stress in trained men.

    PubMed

    McCarthy, Cameron G; Farney, Tyler M; Canale, Robert E; Dessoulavy, Michael E; Bloomer, Richard J

    2013-01-01

    Two prevalent origins of oxidative stress in Western society are the ingestion of high-fat meals and the performance of strenuous exercise. The purpose of this investigation was to compare the magnitude of increase in blood oxidative stress following acute feeding and acute exercise. Twelve exercise-trained men consumed a high-fat meal or performed 1 of 3 exercise bouts (steady-state aerobic; high-intensity, moderate-duration interval sprints; maximal intensity, short-duration interval sprints) in a random order, crossover design. Blood was collected before and at times following feeding and exercise. Samples were analyzed for trigylcerides, malondialdehyde (MDA), hydrogen peroxide (H(2)O(2)), advanced oxidation protein products (AOPP), nitrate/nitrite (NOx), trolox-equivalent antioxidant capacity (TEAC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). A significant condition effect was noted for MDA (p = 0.01), H(2)O(2) (p < 0.0001), and AOPP (p = 0.0006), with values highest for the meal condition. An increase of 88%, 247%, and 96% was noted from pre- to post-feeding for MDA, H(2)O(2), and AOPP, respectively. A condition effect was also noted for TEAC (p = 0.04) and CAT (p = 0.05), with values lowest for the meal condition (TEAC) and the meal and aerobic exercise condition (CAT). NOx, SOD, and GPx were relatively unaffected by feeding and exercise, while MDA, H(2)O(2), and AOPP experienced little change from pre- to postexercise (p > 0.05). These results illustrate that the magnitude of blood oxidative stress following a high-fat meal is significantly greater than that elicited by either aerobic or anaerobic exercise in a sample of exercise-trained men.

  19. Calcium imaging in gentamicin ototoxicity: increased intracellular calcium relates to oxidative stress and late apoptosis.

    PubMed

    Chang, Jiwon; Yang, Ji Yun; Choi, June; Jung, Hak Hyun; Im, Gi Jung

    2011-12-01

    To estimate intracellular calcium changes in gentamicin (GM) ototoxicity using calcium imaging. To investigate GM-induced physiologic changes in auditory cells including cell viability, apoptosis, and oxidative stress. Varying concentrations of GM were applied to the HEI-OC1 cochlear cell line. Calcium imaging tracked changes in intracellular calcium concentration during GM cytotoxicity. Cell viability and intracellular reactive oxygen species (ROS) levels also were measured. Little change in calcium levels occurred in HEI-OC1 cells exposed to less than 35 mM GM. However, calcium rose continuously in cells exposed to more than 60 mM GM. With administration of intermediate concentrations of 40 or 50 mM GM, calcium increased variably in different cells, returning to baseline in some cases, or rising continuously in others. Upon increase of GM concentration, intracellular calcium concentration and ROS were increased, and cell viability was decreased due to late apoptosis. This study shows that GM increased intracellular calcium, ROS, and late apoptosis of HEI-OC1 cells derived from cochlear tissue. Increase of intracellular calcium is related to GM-induced apoptosis and oxidative stress. Calcium imaging can be used to determine change of intracellular calcium concentrations and apoptosis in GM ototoxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis

    PubMed Central

    Wu, Yanqing; Reece, E. Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R.; Yang, Peixin

    2017-01-01

    BACKGROUND Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus–induced congenital heart defects remain largely unknown. OBJECTIVE We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus–induced congenital heart defects. STUDY DESIGN A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. RESULTS Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin

  1. Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.

    PubMed

    Wu, Yanqing; Reece, E Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R; Yang, Peixin

    2016-09-01

    Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown. We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects. A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene

  2. Aldosterone Increases Oxidant Stress to Impair Guanylyl Cyclase Activity by Cysteinyl Thiol Oxidation in Vascular Smooth Muscle Cells*S⃞

    PubMed Central

    Maron, Bradley A.; Zhang, Ying-Yi; Handy, Diane E.; Beuve, Annie; Tang, Shiow-Shih; Loscalzo, Joseph; Leopold, Jane A.

    2009-01-01

    Hyperaldosteronism is associated with impaired endothelium-dependent vascular reactivity owing to increased reactive oxygen species and decreased bioavailable nitric oxide (NO·); however, the effects of aldosterone on vasodilatory signaling pathways in vascular smooth muscle cells (VSMC) remain unknown. Soluble guanylyl cyclase (GC) is a heterodimer that is activated by NO· to convert cytosolic GTP to cGMP, a second messenger required for normal VSMC relaxation. Here, we show that aldosterone (10-9-10-7 mol/liter) diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase reactive oxygen species levels and induce oxidative posttranslational modification(s) of Cys-122, a β1-subunit cysteinyl residue demonstrated previously to modulate NO· sensing by GC. In VSMC treated with aldosterone, Western immunoblotting detected evidence of GC β1-subunit disulfide bonding, whereas mass spectrometry analysis of a homologous peptide containing the Cys-122-bearing sequence exposed to conditions of increased oxidant stress confirmed cysteinyl sulfinic acid (m/z 435), sulfonic acid (m/z 443), and disulfide (m/z 836) bond formation. The functional effect of these modifications was examined by transfecting COS-7 cells with wild-type GC or mutant GC containing an alanine substitution at Cys-122 (C122A). Exposure to aldosterone or hydrogen peroxide (H2O2) significantly decreased cGMP levels in cells expressing wild-type GC. In contrast, aldosterone or H2O2 did not influence cGMP levels in cells expressing the mutant C122A GC, confirming that oxidative modification of Cys-122 specifically impairs GC activity. These findings demonstrate that pathophysiologically relevant concentrations of aldosterone increase oxidant stress to convert GC to an NO·-insensitive state, resulting in disruption of normal vasodilatory signaling pathways in VSMC. PMID:19141618

  3. Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased oxidative stress in mice

    PubMed Central

    Bonilha, Vera L.; Bell, Brent A.; Rayborn, Mary E.; Yang, Xiaoping; Kaul, Charlie; Grossman, Gregory H.; Samuels, Ivy S.; Hollyfield, Joe G.; Xie, Chengsong; Cai, Huaibin; Shadrach, Karen G.

    2015-01-01

    DJ-1/PARK7 mutations or deletions cause autosomal recessive early onset Parkinson’s disease (PD). Thus, DJ-1 protein has been extensively studied in brain and neurons. PD patients display visual symptoms; however, the visual symptoms specifically attributed to PD patients carrying DJ-1/PARK7 mutations are not known. In this study, we analyzed the structure and physiology of retinas of 3- and 6-month-old DJ-1 knockout (KO) mice to determine how loss of function of DJ-1 specifically contributes to the phenotypes observed in PD patients. As compared to controls, the DJ-1 KO mice displayed an increase in the amplitude of the scotopic ERG b-wave and cone ERG, while the amplitude of a subset of the dc-ERG components were decreased. The main structural changes in the DJ-1 KO retinas were found in the outer plexiform layer (OPL), photoreceptors and retinal pigment epithelium (RPE), which were observed at 3 months and progressively increased at 6 months. RPE thinning and structural changes within the OPL were observed in the retinas in DJ-1 KO mice. DJ-1 KO retinas also exhibited disorganized outer segments, central decrease in red/green cone opsin staining, decreased labeling of ezrin, broader distribution of ribeye labeling, decreased tyrosine hydroxylase in dopaminergic neurons, and increased 7,8- dihydro-8-oxoguanine-labeled DNA oxidation. Accelerated outer retinal atrophy was observed in DJ-1 KO mice after selective oxidative damage induced by a single tail vein injection of NaIO3, exposing increased susceptibility to oxidative stress. Our data indicate that DJ-1-deficient retinas exhibit signs of morphological abnormalities and physiological dysfunction in association with increased oxidative stress. Degeneration of RPE cells in association with oxidative stress is a key hallmark of age-related macular degeneration (AMD). Therefore, in addition to detailing the visual defects that occur as a result of the absence of DJ-1, our data is also relevant to AMD

  4. Impaired genomic stability and increased oxidative stress exacerbate different features of Ataxia-telangiectasia.

    PubMed

    Ziv, Shelly; Brenner, Ori; Amariglio, Ninette; Smorodinsky, Nechama I; Galron, Ronit; Carrion, Danaise V; Zhang, Weijia; Sharma, Girdhar G; Pandita, Raj K; Agarwal, Manjula; Elkon, Ran; Katzin, Nirit; Bar-Am, Irit; Pandita, Tej K; Kucherlapati, Raju; Rechavi, Gideon; Shiloh, Yosef; Barzilai, Ari

    2005-10-01

    Ataxia-telangiectasia (A-T) is a multisystem, cancer-predisposing genetic disorder caused by deficiency of the ATM protein. To dissect the A-T phenotype, we augmented specific features of the human disease by generating mouse strains that combine Atm deficiency with dysfunction of other proteins. Increasing oxidative stress by combining deficiencies in Atm and superoxide dismutase 1 (Sod1) exacerbated growth retardation and markedly reduced the mean survival time following ionizing radiation. In contrast, increasing genomic instability by combining deficiencies of Atm and the mismatch repair protein Mlh1 caused a moderate increase in radiation sensitivity and dramatic increase in aggressive lymphomas, compared with thes Atm-/- single knockout. Remarkably, Atm, Mlh1 or Mlh1/Atm single or double heterozygosity did not significantly affect the life span of the various genotypes. Mlh1/Atm double null tumors were polyclonal, whereas the tumors in other genotypes were mono- or oligoclonal, demonstrating the high predisposition of thymocytes with this genotype to become malignant. Chromosomal aberrations in the tumors were localized mainly in chromosomes 12 and 15. The genomic region on chromosome 15, which contains the gene for the c-Myc oncoprotein, was commonly amplified, and elevated levels of the c-Myc protein were subsequently observed in the tumors. Our data suggest that impaired genomic instability is an important contributing factor to cancer predisposition in A-T, whereas oxidative stress is more important in the radiation sensitivity and growth retardation facets of this disease.

  5. Increased Mutability of Staphylococci in Biofilms as a Consequence of Oxidative Stress

    PubMed Central

    Ryder, Victoria J.; Chopra, Ian; O’Neill, Alex J.

    2012-01-01

    Objectives To investigate the development of mutational resistance to antibiotics in staphylococcal biofilms. Methods Mutation frequencies to resistance against mupirocin and rifampicin were determined for planktonic cultures and for biofilms generated using either a novel static biofilm model or by continuous flow. DNA microarray analysis was performed to detect differences in transcriptional profiles between planktonic and biofilm cultures. Results The mutability of biofilm cultures increased up to 60-fold and 4-fold for S. aureus and S. epidermidis, respectively, compared with planktonic cultures. Incorporation of antioxidants into S. aureus biofilms reduced mutation frequencies, indicating that increased oxidative stress underlies the heightened mutability. Transcriptional profiling of early biofilm cultures revealed up-regulation of the superoxide dismutase gene, sodA, also suggestive of enhanced oxidative stress in these cultures. The addition of catalase to biofilms of S. aureus SH1000 reduced mutation frequencies, a finding which implicated hydrogen peroxide in increased biofilm mutability. However, catalase had no effect on biofilm mutability in S. aureus UAMS-1, suggesting that there is more than one mechanism by which the mutability of staphylococci may increase during the biofilm mode of growth. Conclusion Our findings suggest that biofilms represent an enriched source of mutational resistance to antibiotics in the staphylococci. PMID:23110091

  6. Hepatic Mitochondrial Alterations and Increased Oxidative Stress in Nutritional Diabetes-Prone Psammomys obesus Model

    PubMed Central

    Bouderba, Saida; Sanz, M. Nieves; Sánchez-Martín, Carlos; El-Mir, M. Yehia; Villanueva, Gloria R.; Detaille, Dominique; Koceïr, E. Ahmed

    2012-01-01

    Mitochondrial dysfunction is considered to be a pivotal component of insulin resistance and associated metabolic diseases. Psammomys obesus is a relevant model of nutritional diabetes since these adult animals exhibit a state of insulin resistance when fed a standard laboratory chow, hypercaloric for them as compared to their natural food. In this context, alterations in bioenergetics were studied. Using liver mitochondria isolated from these rats fed such a diet for 18 weeks, oxygen consumption rates, activities of respiratory complexes, and content in cytochromes were examined. Levels of malondialdehyde (MDA) and gluthatione (GSH) were measured in tissue homogenates. Diabetic Psammomys showed a serious liver deterioration (hepatic mass accretion, lipids accumulation), accompanied by an enhanced oxidative stress (MDA increased, GSH depleted). On the other hand, both ADP-dependent and uncoupled respirations greatly diminished below control values, and the respiratory flux to cytochrome oxydase was mildly lowered. Furthermore, an inhibition of complexes I and III together with an activation of complex II were found. With emergence of oxidative stress, possibly related to a defect in oxidative phosphorylation, some molecular adjustments could contribute to alleviate, at least in part, the deleterious outcomes of insulin resistance in this gerbil species. PMID:22675340

  7. Increased oxidative stress in subjects exposed to carbon disulfide (CS2)--an occupational coronary risk factor.

    PubMed

    Wronska-Nofer, Teresa; Chojnowska-Jezierska, Julita; Nofer, Jerzy-Roch; Halatek, Tadeusz; Wisniewska-Knypl, Justyna

    2002-04-01

    There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) develop premature atherosclerosis leading to increased rates of coronary heart disease (CHD), but mechanisms underlying this association remain obscure. The present study documents that occupational exposure to CS2 modifies the oxidative status of plasma, which is a major determinant of the susceptibility to atherosclerosis. Concentrations of thiobarbituric reactive substances (TBARS), which reflect lipid peroxidation processes in plasma, were determined in 29 men who were exposed to CS2 for more than 20 years, in 24 patients with peripheral atherosclerosis, and in 30 unexposed, healthy control subjects. TBARS concentrations were significantly increased both in CS2-exposed subjects and in patients with peripheral atherosclerosis. Subjects in both groups presented also with decreased levels of plasma alpha-tocopherol, a major plasma antioxidant. In addition, decreased activities of two enzymatic antioxidants, glutathion peroxidase and catalase, were noted both in CS2-exposed subjects and patients with peripheral atherosclerosis. Finally, LDL isolated from both groups showed increased susceptibility to transition metal-induced oxidation in vitro. It is concluded, that occupational exposure to CS2 produces oxidative stress in plasma. This may favor the development of atherosclerosis and increase the incidence of CHD in workers exposed to CS2.

  8. Increasing the Oxidative Stress Response Allows Escherichia coli To Overcome Inhibitory Effects of Condensed Tannins

    PubMed Central

    Smith, Alexandra H.; Imlay, James A.; Mackie, Roderick I.

    2003-01-01

    Tannins are plant-derived polyphenols with antimicrobial effects. The mechanism of tannin toxicity towards Escherichia coli was determined by using an extract from Acacia mearnsii (Black wattle) as a source of condensed tannins (proanthocyanidins). E. coli growth was inhibited by tannins only when tannins were exposed to oxygen. Tannins auto-oxidize, and substantial hydrogen peroxide was generated when they were added to aerobic media. The addition of exogenous catalase permitted growth in tannin medium. E. coli mutants that lacked HPI, the major catalase, were especially sensitive to tannins, while oxyR mutants that constitutively overexpress antioxidant enzymes were resistant. A tannin-resistant mutant was isolated in which a promoter-region point mutation increased the level of HPI by 10-fold. Our results indicate that wattle condensed tannins are toxic to E. coli in aerobic medium primarily because they generate H2O2. The oxidative stress response helps E. coli strains to overcome their inhibitory effect. PMID:12788743

  9. Elimination of damaged mitochondria through mitophagy reduces mitochondrial oxidative stress and increases tolerance to trichothecenes.

    PubMed

    Bin-Umer, Mohamed Anwar; McLaughlin, John E; Butterly, Matthew S; McCormick, Susan; Tumer, Nilgun E

    2014-08-12

    Trichothecene mycotoxins are natural contaminants of small grain cereals and are encountered in the environment, posing a worldwide threat to human and animal health. Their mechanism of toxicity is poorly understood, and little is known about cellular protection mechanisms against trichothecenes. We previously identified inhibition of mitochondrial protein synthesis as a novel mechanism for trichothecene-induced cell death. To identify cellular functions involved in trichothecene resistance, we screened the Saccharomyces cerevisiae deletion library for increased sensitivity to nonlethal concentrations of trichothecin (Tcin) and identified 121 strains exhibiting higher sensitivity than the parental strain. The largest group of sensitive strains had significantly higher reactive oxygen species (ROS) levels relative to the parental strain. A dose-dependent increase in ROS levels was observed in the parental strain treated with different trichothecenes, but not in a petite version of the parental strain or in the presence of a mitochondrial membrane uncoupler, indicating that mitochondria are the main site of ROS production due to toxin exposure. Cytotoxicity of trichothecenes was alleviated after treatment of the parental strain and highly sensitive mutants with antioxidants, suggesting that oxidative stress contributes to trichothecene sensitivity. Cotreatment with rapamycin and trichothecenes reduced ROS levels and cytotoxicity in the parental strain relative to the trichothecene treatment alone, but not in mitophagy deficient mutants, suggesting that elimination of trichothecene-damaged mitochondria by mitophagy improves cell survival. These results reveal that increased mitophagy is a cellular protection mechanism against trichothecene-induced mitochondrial oxidative stress and a potential target for trichothecene resistance.

  10. Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

    PubMed

    Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

    2016-01-01

    Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

  11. Tetrahydrobiopterin, L-arginine and vitamin C act synergistically to decrease oxidant stress and increase nitric oxide that increases blood flow recovery after hindlimb ischemia in the rat.

    PubMed

    Yan, Jinglian; Tie, Guodong; Messina, Louis M

    2012-10-24

    Nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is a potent vasodilator and signaling molecule that plays essential roles in neovascularization. During limb ischemia, decreased NO bioavailability occurs secondary to increased oxidant stress, decreased L-arginine and tetrahydrobiopterin. This study tested the hypothesis that dietary cosupplementation with tetrahydrobiopterin (BH4), L-arginine and vitamin C acts synergistically to decrease oxidant stress, increase NO and thereby increase blood flow recovery after hindlimb ischemia. Rats were fed normal chow, chow supplemented with BH4 or L-arginine (alone or in combination) or chow supplemented with BH4 + L-arginine + vitamin C for 1 wk before induction of hindlimb ischemia. In the is-chemic hindlimb, cosupplementation with BH4 + L-arginine resulted in greater eNOS and phospho-eNOS (P-eNOS) expression, Ca(2+)-dependent NOS activity and NO concentration in the ischemic calf region (gastrocnemius), as well as greater NO concentration in the region of collateral arteries (gracilis). Rats receiving cosupplementation of BH4 + L-arginine led to greater recovery of foot perfusion and greater collateral enlargement than did rats receiving either agent separately. The addition of vitamin C to the BH4 + L-arginine regimen further increased these dependent variables. In addition, rats given all three supplements showed significantly less Ca(2+)-independent activity, less nitrotyrosine accumulation, greater glutathione (GSH)-to-glutathione disulfide (GSSG) ratio and less gastrocnemius muscle necrosis, on both macroscopic and microscopic levels. In conclusion, co-supplementation with BH4 + L-arginine + vitamin C significantly increased blood flow recovery after hindlimb ischemia by reducing oxidant stress, increasing NO bioavailability, enlarging collateral arteries and reducing muscle necrosis. Oral cosupplementation of BH4, L-arginine and vitamin C holds promise as a biological therapy to induce

  12. Increase in oxidative stress and mitochondrial impairment in hypothalamus of streptozotocin treated diabetic rat: Antioxidative effect of Withania somnifera.

    PubMed

    Parihar, P; Shetty, R; Ghafourifar, P; Parihar, M S

    2016-01-22

    Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat.

  13. Increased levels of oxidative stress biomarkers in metal oxides nanomaterial-handling workers.

    PubMed

    Liou, Saou-Hsing; Chen, Yu-Cheng; Liao, Hui-Yi; Wang, Chien-Jen; Chen, Jhih-Sheng; Lee, Hui-Ling

    2016-11-01

    This study assessed oxidatively damaged DNA and antioxidant enzyme activity in workers occupational exposure to metal oxides nanomaterials. Exposure to TiO2, SiO2, and ITO resulted in significant lower antioxidant enzymes (glutathione peroxidase and superoxide dismutase) and higher oxidative biomarkers 8-hydroxydeoxyguanosine (8-oxodG) than comparison workers. Statistically significant correlations were noted between plasma and urine 8-oxodG, between white blood cells (WBC) and urine 8-oxodG, and between WBC and plasma 8-oxodG. In addition, there were significant negative correlations between WBC 8-oxodG and SOD and between urinary 8-oxodG and GPx levels. The results showed that urinary 8-oxodG may be considered to be better biomarker.

  14. Cutaneous interstitial nitric oxide concentration does not increase during heat stress in humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; MacLean, D. A.

    2001-01-01

    Inhibition of cutaneous nitric oxide (NO) synthase reduces the magnitude of cutaneous vasodilation during whole body heating in humans. However, this observation is insufficient to conclude that NO concentration increases in the skin during a heat stress. This study was designed to test the hypothesis that whole body heating increases cutaneous interstitial NO concentration. This was accomplished by placing 2 microdialysis membranes in the forearm dermal space of 12 subjects. Both membranes were perfused with lactated Ringer solutions at a rate of 2 microl/min. In both normothermia and during whole body heating via a water perfused suit, dialysate from these membranes were obtained and analyzed for NO using the chemiluminescence technique. In six of these subjects, after the heat stress, the membranes were perfused with a 1 M solution of acetylcholine to stimulate NO release. Dialysate from these trials was also assayed to quantify cutaneous interstitial NO concentration. Whole body heating increased skin temperature from 34.6 +/- 0.2 to 38.8 +/- 0.2 degrees C (P < 0.05), which increased sublingual temperature (36.4 +/- 0.1 to 37.6 +/- 0.1 degrees C; P < 0.05), heart rate (63 +/- 5 to 93 +/- 5 beats/min; P < 0.05), and skin blood flow over the membranes (21 +/- 4 to 88 +/- 10 perfusion units; P < 0.05). NO concentration in the dialysate did not increase significantly during of the heat stress (7.6 +/- 0.7 to 8.6 +/- 0.8 microM; P > 0.05). After the heat stress, administration of acetylcholine in the perfusate significantly increased skin blood flow (128 +/- 6 perfusion units) relative to both normothermic and heat stress values and significantly increased NO concentration in the dialysate (15.8 +/- 2.4 microM). These data suggest that whole body heating does not increase cutaneous interstitial NO concentration in forearm skin. Rather, NO may serve in a permissive role in facilitating the effects of an unknown neurotransmitter, leading to cutaneous vasodilation

  15. Cutaneous interstitial nitric oxide concentration does not increase during heat stress in humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; MacLean, D. A.

    2001-01-01

    Inhibition of cutaneous nitric oxide (NO) synthase reduces the magnitude of cutaneous vasodilation during whole body heating in humans. However, this observation is insufficient to conclude that NO concentration increases in the skin during a heat stress. This study was designed to test the hypothesis that whole body heating increases cutaneous interstitial NO concentration. This was accomplished by placing 2 microdialysis membranes in the forearm dermal space of 12 subjects. Both membranes were perfused with lactated Ringer solutions at a rate of 2 microl/min. In both normothermia and during whole body heating via a water perfused suit, dialysate from these membranes were obtained and analyzed for NO using the chemiluminescence technique. In six of these subjects, after the heat stress, the membranes were perfused with a 1 M solution of acetylcholine to stimulate NO release. Dialysate from these trials was also assayed to quantify cutaneous interstitial NO concentration. Whole body heating increased skin temperature from 34.6 +/- 0.2 to 38.8 +/- 0.2 degrees C (P < 0.05), which increased sublingual temperature (36.4 +/- 0.1 to 37.6 +/- 0.1 degrees C; P < 0.05), heart rate (63 +/- 5 to 93 +/- 5 beats/min; P < 0.05), and skin blood flow over the membranes (21 +/- 4 to 88 +/- 10 perfusion units; P < 0.05). NO concentration in the dialysate did not increase significantly during of the heat stress (7.6 +/- 0.7 to 8.6 +/- 0.8 microM; P > 0.05). After the heat stress, administration of acetylcholine in the perfusate significantly increased skin blood flow (128 +/- 6 perfusion units) relative to both normothermic and heat stress values and significantly increased NO concentration in the dialysate (15.8 +/- 2.4 microM). These data suggest that whole body heating does not increase cutaneous interstitial NO concentration in forearm skin. Rather, NO may serve in a permissive role in facilitating the effects of an unknown neurotransmitter, leading to cutaneous vasodilation

  16. Is the titer of adipokinetic peptides in Leptinotarsa decemlineata fed on genetically modified potatoes increased by oxidative stress?

    PubMed

    Kodrík, Dalibor; Krishnan, Natraj; Habustová, Oxana

    2007-05-01

    The level of adipokinetic hormones (AKHs) (Peram-CAH-I and II) in the corpora cardiaca and the hemolymph of Leptinotarsa decemlineata enormously increases in the adults fed on genetically modified potatoes containing either GNA lectin or Cry 3Aa toxin concomitant with increased oxidative stress in gut tissues. A similar enhancement of the AKH titer is achieved when the adults are injected with paraquat that evokes oxidative stress. On the other hand, an injection of exogenous AKH reduces oxidative stress biomarkers in the hemolymph by reducing protein carbonyls and enhancing reduced glutathione levels. These facts indicate that there is a feedback regulation between an oxidative stressor action and the level of AKH in the insect body, and that AKHs might be involved in the activation of an antioxidant protection mechanism. These results are to our knowledge, the first evidence for the involvement of AKHs in oxidative stress mitigation, in addition to a plethora of other roles.

  17. Increase in Levels of BDNF is Associated with Inflammation and Oxidative Stress during Cardiopulmonary Bypass

    PubMed Central

    Amoureux, Sébastien; Sicard, Pierre; Korandji, Claudia; Borey, Angélique; Benkhadra, Salima; Sequeira-Le Grand, Anabelle; Vergely, Catherine; Girard, Claude; Rochette, Luc

    2008-01-01

    Cardiopulmonary Bypass (CPB) is thought to generate reactive oxygen species associated with a systemic inflammation and neurotrophins seem to be involved in cardiovascular inflammatory reactions. The aim of this study was to determine the impact of CPB on plasma neurotrophins levels and to appreciate the links existing between inflammation, oxidative stress and neurotrophins. Blood samples were taken from 27 patients undergoing cardiac surgery: before CPB, during ischemia and at reperfusion under CPB. Oxidative stress was evaluated using an Electron Spin Resonance technique by superoxide detection, and antioxidant defences by measurement of Endogenous Peroxidase Activity (EPA). The evolution of two neurotrophins: Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) was assessed with an ELISA method. An inflammatory index was determined by a multiplex flow cytometry method. The inflammatory index showed that MCP-1, P-selectin, t-PA and interleukins 6, 8 and 10 levels increased during CPB (p<0.05). Superoxide production and EPA were higher during ischemia and reperfusion than before CPB (p<0.05). BDNF plasma levels were higher at reperfusion (p<0.05). NGF levels did not change. Our study shows an increase of BDNF levels, associated with an inflammatory phenomenon and a redox modification, in the plasma of patients undergoing cardiac surgery under CPB. The role played by this neurotrophin in this complex situation still needs to be elucidated, in particular its cellular origin. It is also necessary to understand whether BDNF has a beneficial or deleterious effect during CPB. PMID:23675091

  18. Ischaemic Priapism and Glucose-6-Phosphate Dehydrogenase Deficiency: A Mechanism of Increased Oxidative Stress?

    PubMed

    Morrison, B F; Thompson, E B; Shah, S D; Wharfe, G H

    2014-07-03

    Ischaemic priapism is a devastating urological condition that has the potential to cause permanent erectile dysfunction. The disorder has been associated with numerous medical conditions and the use of pharmacotherapeutic agents. The aetiology is idiopathic in a number of cases. There are two prior case reports of the association of ischaemic priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report on a third case of priapism associated with G6PD deficiency and review recently described molecular mechanisms of increased oxidative stress in the pathophysiology of ischaemic priapism. The case report of a 32-year old Afro-Caribbean male with his first episode of major ischaemic priapism is described. Screening for common causes of ischaemic priapism, including sickle cell disease was negative. Glucose-6-phosphate dehydrogenase deficiency was discovered on evaluation for priapism. Penile aspiration was performed and erectile function was good post treatment.Glucose-6-phosphate dehydrogenase deficiency is a cause for ischaemic priapism and should be a part of the screening process in idiopathic causes of the disorder. Increased oxidative stress occurs in G6PD deficiency and may lead to priapism.

  19. Washing increases the susceptibility to exogenous oxidative stress in red deer spermatozoa.

    PubMed

    Domínguez-Rebolledo, A E; Fernández-Santos, M R; García-Alvarez, O; Maroto-Morales, A; Garde, J J; Martínez-Pastor, F

    2009-11-01

    The effects of routine sperm work are often overlooked. We assessed the effect of washing cryopreserved epididymal spermatozoa from red deer (Cervus elaphus hispanicus, Helzheimer 1909). After thawing, epididymal samples (four stags) were diluted in TALP-HEPES. A split was left untouched, another was centrifuged (300 x g, 5 min) and resuspended, and a third was centrifuged and the supernatant substituted by fresh TALP-HEPES (washing). Each split was supplemented either with nothing, 1mM of the antioxidant Trolox, 100 microM of the oxidant Fe (with ascorbate), or both. The 3x4 treatments were incubated at 37 degrees C and assessed each hour up to 3h for motility (computer-aided sperm assessment) and viability/apoptosis plus mitochondrial status (YO-PRO-1, propidium iodide, Mitotracker Deep Red; flow cytometry). DNA damage at 4h was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Centrifugation alone affected neither sperm quality nor DNA, and the oxidant had no effect in control or centrifuged samples. Washed samples were not different than control, but oxidant decreased motility, mitochondrial status and viability, and altered the motility subpopulation pattern, being partially suppressed by Trolox. Spermatozoa with damaged DNA dramatically increased in the washed-oxidized sample (from 22.30+/-3.52% to 67.94+/-5.07%), but not when antioxidant was present. Although samples from different males behaved similarly, male-to-male variability was detected regarding susceptibility to oxidative damage after washing. We concluded that, although red deer thawed spermatozoa seemed resilient to centrifugation, the vulnerability to oxidative stress after washing makes it advisable to supplement manipulation media with antioxidants, especially taking into account male-to-male variability.

  20. Honey Bee (Apis mellifera) Drones Survive Oxidative Stress due to Increased Tolerance instead of Avoidance or Repair of Oxidative Damage

    PubMed Central

    Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K.; Tarpy, David R.; Rueppell, Olav

    2016-01-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. PMID:27422326

  1. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.

    PubMed

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-03-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.

  2. 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

  3. Oxidative stress is increased in C. elegans models of Huntington's disease but does not contribute to polyglutamine toxicity phenotypes.

    PubMed

    Machiela, Emily; Dues, Dylan J; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-12-01

    Huntington's disease (HD) is an adult onset neurodegenerative disorder for which there is currently no cure. While HD patients and animal models of the disease exhibit increased oxidative damage, it is currently uncertain to what extent oxidative stress contributes to disease pathogenesis. In this work, we use a genetic approach to define the role of oxidative stress in HD. We find that a C. elegans model of HD expressing a disease-length polyglutamine tract in the body wall muscle is hypersensitive to oxidative stress and shows an upregulation of antioxidant defense genes, indicating that the HD worm model has increased levels of oxidative stress. To determine whether this increase in oxidative stress contributes to the development of polyglutamine-toxicity phenotypes in this HD model, we examined the effect of deleting individual superoxide dismutase (sod) genes in the HD worm model. As predicted, we found that deletion of sod genes in the HD worm model resulted in a clear increase in sensitivity to oxidative stress. However, we found that increasing oxidative stress in the HD worm model did not exacerbate deficits caused by polyglutamine toxicity. We confirmed these observations in two worm models expressing disease-length polyglutamine tracts in neurons. Furthermore, we found that treatment with antioxidants failed to rescue movement deficits or decrease aggregation in HD worm models. Combined, this suggests that the increase in oxidative stress in worm models of HD does not contribute to the phenotypic deficits observed in these worms, and provides a possible explanation for the failure of antioxidants in HD clinical trials.

  4. Pressure promotes angiotensin II--mediated migration of human coronary smooth muscle cells through increase in oxidative stress.

    PubMed

    Yasunari, Kenichi; Maeda, Kensaku; Nakamura, Munehiro; Yoshikawa, Junichi

    2002-02-01

    Angiotensin II--mediated oxidative stress may play a role in the pathogenesis of coronary atherosclerosis. We examined the effects of pressure on the angiotensin II--mediated increase in oxidative stress and migration of cultured human coronary smooth muscle cells (SMCs). Increased pressure (100 mm Hg) by helium gas for 48 hours increased angiotensin II--mediated oxidative stress as evaluated by flow cytometry and SMC migration (from 15.9 +/- 2.2 to 32.0 +/- 2.4 cells per 4 high-power fields, P<0.05; n=8). The pressure-induced increases in oxidative stress observed appear to involve phospholipase D (PLD) and protein kinase C (PKC), inasmuch as the indirect PLD inhibitor suramin, at 100 micromol/L, and the PKC inhibitor chelerythrine, at 1 micromol/L, completely blocked the increase in angiotensin II--mediated oxidative stress induced by pressure. Pressure-induced increase in angiotensin II--mediated oxidative stress was inhibited by diphenylene iodonium chloride, an NADPH oxidase inhibitor, by 79% (P<0.05, n=8). Losartan (1 micromol/L), its active metabolite E3174 (1 micromol/L), and the antioxidant N-acetylcysteine (100 mmol/L) but not PD123319 (1 micromol/L) also blocked pressure-induced increases in angiotensin II--mediated oxidative stress and SMC migration (P<0.05, n=8). These findings suggest a novel cellular mechanism whereby pressure regulates the angiotensin II--mediated migration of SMCs, possibly via angiotensin II type 1 receptors, and which involves PLD-mediated, PKC-mediated, and NADPH oxidase--mediated increases in oxidative stress.

  5. Local Oxidative and Nitrosative Stress Increases in the Microcirculation during Leukocytes-Endothelial Cell Interactions

    PubMed Central

    Kar, Saptarshi; Kavdia, Mahendra

    2012-01-01

    Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O2•−) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O2•− and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O2•− and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O2•− and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ∼0.6 fold, O2•− increased ∼27 fold and peroxynitrite increased ∼30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase

  6. Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

    PubMed

    Emelyanova, Larisa; Ashary, Zain; Cosic, Milanka; Negmadjanov, Ulugbek; Ross, Gracious; Rizvi, Farhan; Olet, Susan; Kress, David; Sra, Jasbir; Tajik, A Jamil; Holmuhamedov, Ekhson L; Shi, Yang; Jahangir, Arshad

    2016-07-01

    Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF. Copyright © 2016 the American Physiological Society.

  7. Increased oxidative stress in exudative pleural effusions: a new marker for the differentiation between exudates and transudates?

    PubMed

    Papageorgiou, Evangelia; Kostikas, Konstantinos; Kiropoulos, Theodoros; Karetsi, Eleni; Mpatavanis, Georgios; Gourgoulianis, Konstantinos I

    2005-11-01

    Oxidative stress has been associated with various respiratory disorders. We tested the hypothesis that exudates would present higher levels of oxidative stress compared to transudates, expressing the increased local oxidative burst in the former. Prospective, cross-sectional study. One hundred six consecutive patients who had undergone thoracentesis were studied. Ninety patients with a final diagnosis of pleural effusion were further analyzed. The respiratory department and a clinical laboratory of a tertiary hospital. Subjects underwent diagnostic thoracentesis, and standard biochemical parameters (ie, total protein, lactate dehydrogenase, and albumin levels) were measured in pleural fluid and serum. Oxidative stress levels were assessed with a commercially available method (d-ROMs test; Diacron; Grosseto, Italy) that uses conventional Carratelli units (UCarr). In 14 patients, duplicate measurements of oxidative stress and a second thoracentesis were performed on the following day for the assessment of the repeatability of measurements. Receiver operating characteristic (ROC) analysis was performed in order to determine the optimal cutoff level for the differentiation between exudates and transudates. Oxidative stress levels were higher in exudates compared to transudates (mean [+/- SD] stress level, 274 +/- 72 vs 126 +/- 34 UCarr, respectively; p < 0.0001). No significant differences were found among the levels of oxidative stress in exudative effusions of different etiologies. The area under the ROC curve was 0.992 (95% confidence interval, 0.945 to 0.997), and the method provided high sensitivity (96.8%), high specificity (96.3%), and high accuracy (96.7%) for the diagnosis of exudates at a cutoff level for oxidative stress of 186 UCarr. Consecutive measurements of oxidative stress in the same samples and on fluid from two different thoracenteses performed on 2 consecutive days presented excellent repeatability. Oxidative stress levels are higher in exudative

  8. Altered detoxification status and increased resistance to oxidative stress by K-ras transformation.

    PubMed

    Recktenwald, Christian V; Kellner, Roland; Lichtenfels, Rudolf; Seliger, Barbara

    2008-12-15

    Mutated K-ras is frequently found in human malignancies and plays a key role in many signal transduction processes resulting in an altered gene and/or protein expression pattern. Proteins controlled by a constitutive activated mitogen-activated protein kinase pathway are primarily related to alterations in the mitochondrial and nuclear compartments. Therefore, different K-Ras mutants and respective control cells were subjected to two-dimensional gel electrophoresis using basic pH gradients. This approach led to the identification of differentially expressed proteins, such as members of the heterogeneous ribonucleoprotein family, and enzymes involved in cellular detoxification as well as in oxidative stress. Increased expression of these enzymes was paralleled by an elevated tolerance of K-ras mutants against the cytotoxic potential of hydrogen peroxide and formaldehyde as well as an altered redox status based on enhanced intracellular glutathione (GSH) levels indicating an improved detoxification potential of defined K-ras transfectants, whereas down-regulation by RNA interference of candidate proteins reversed the tolerance against these compounds. This hypothesis is supported by an up-regulated expression of a key enzyme of the pentose phosphate pathway resulting in an increased production of NADPH required for anabolic processes as well as the rebuilding of oxidized GSH. Both the enhanced resistance against xenobiotic compounds as well as an altered oxidative pathway might confer growth advantages for tumor cells carrying dominant-positive K-ras mutations such as in lung or pancreatic adenocarcinoma.

  9. Increased oxidative stress and plasma Hsp70 levels among gasoline filling station attendants.

    PubMed

    Xia, Bing; Chen, Kangcheng; Lv, Yingnan; Huang, Damin; Liu, Jing; Liang, Guiqiang; Zhang, Li'e; Wang, Fenfen; Su, Cheng; Zou, Yunfeng; Yang, Xiaobo

    2017-02-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic derivative of manganese (Mn) and is used as an antiknock agent and octane enhancer in gasoline. In this article, we tested the oxidative stress and heat stress protein (Hsp) 70 levels of gasoline station attendants to explore potential plasma biomarkers. Furthermore, the dose-response relationship was also identified. A total of 144 workers, including 96 petrol fillers and 48 cashiers, participated in the study. Ambient concentrations of benzene, toluene, ethylbenzene, and xylene (BTEX) and Mn were monitored at nine filling stations. During the measuring process, the individual cumulative exposure index was calculated. Plasma oxidative stress and Hsp70 levels were also analysed using enzyme-linked immunosorbent assay. The BTEX time-weighted average in office areas was significantly lower than in refuelling areas ( p < 0.05). In refuelling areas, the content of Mn ranged from 6.44 μg/m(3) to 127.34 μg/m(3), which was much higher than that in office areas (3.16-7.22 μg/m(3); p < 0.05). Exposed workers had significantly different plasma oxidative stress indicators compared with the control group, respectively: superoxide dismutase (SOD), 39.18 ± 6.05 U/mL versus 52.84 ± 3.87 U/mL; glutathione peroxidase (GSH-Px), 186.07 ± 15.63 U versus 194.38 ± 10.42 U; and malondialdehyde (MDA), 1.68 ± 0.52 nmol/L versus 1.43 ± 0.64 nmol/L (in all comparisons, p < 0.05). Plasma Hsp70 level in the exposed group (2.77 ± 0.64 ng/mL) was significantly higher than in the control group (2.32 ± 0.87 ng/mL; p < 0.05). Furthermore, Hsp70 levels were inversely correlated with the activities of SOD ( r = -0.305) and GSH-Px ( r = -0.302) in the exposed group ( p < 0.05). Moreover, a positive correlation ( r = 0.653) was found between plasma Hsp70 levels and plasma MDA levels ( p < 0.05). Exposure to MMT-containing gasoline may result in increasing reactive oxygen stress among filling station attendants. Plasma Hsp70

  10. Increased oxidative stress from early pregnancy in women who develop preeclampsia.

    PubMed

    D'Souza, Vandita; Rani, Alka; Patil, Vidya; Pisal, Hemlata; Randhir, Karuna; Mehendale, Savita; Wagh, Girija; Gupte, Sanjay; Joshi, Sadhana

    2016-01-01

    Preeclampsia (PE) is a pregnancy-specific disorder, defined as new onset of maternal hypertension and proteinuria after 20 weeks of gestation. Our earlier study has shown increased maternal oxidative stress at delivery to be associated with poor birth outcome in PE. However, these results were observed when the pathology had progressed and may have been secondary to the effects of the disorder. To understand the role of antioxidant defense mechanisms in PE right from early pregnancy, in this prospective study, we measured malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) concentrations in maternal blood at 3 time-points of gestation [16-20 weeks (T1), 26-30 weeks (T2), at delivery (T3)] and in cord blood. Gene expression of SOD and GPx and protein levels of endothelial nitric oxide synthase (eNOS) enzyme were also analyzed in the placenta. MDA levels were higher at T1 (p < 0.01) and T2 (p < 0.01) in women with PE as compared with control. GPx levels were higher at T3 (p < 0.05) while SOD levels were lower at T2 (p < 0.05), T3 (p < 0.01) and in cord (p < 0.01) in PE. GSH levels at T1 (p < 0.05) and expression of GPx in the placenta were lower in PE as compared with control. In conclusion, this study demonstrates that women who develop PE exhibit increased oxidative stress right from 16 to 20 weeks of gestation. This may alter placental development and lead to fetal programming of adult non-communicable disease in the offspring.

  11. BUBR1 Insufficiency in Mice Increases their Sensitivity to Oxidative Stress.

    PubMed

    Matsuda, Daisuke; Matsumoto, Takuya; Honma, Kenichi; Ikawa-Yoshida, Ayae; Onimaru, Mitsuho; Furuyama, Tadashi; Nakatsu, Yoshimichi; Tsuzuki, Teruhisa; Maehara, Yoshihiko

    Budding uninhibited by benzimidazole-related 1 (BUBR1) plays an important role in the spindle assembly checkpoint to prevent chromosome missegregation and aneuploidy during mitosis. We previously generated mutant mice that express BUBR1 at only 20% of the normal level (BubR1(L/L) mice). Here, we examined the effect of low BUBR1 expression on oxidative stress-induced carcinogenesis in mice. We orally administered either a potassium bromate (KBrO3) solution (2 g/l) or tap water to BubR1(L/L) and wild-type (BubR1(+/+))mice for 16 weeks and examined the subsequent incidence of tumours. KBrO3-treated BubR1(L/L) mice showed significantly higher mortality than the KBrO3-treated BubR1(+/+) and control tap water-treated mice (p=0.0082). Histopathological and immunohistochemical analyses revealed that the spleens of surviving BubR1L/L mice were occupied by non-B-, non-T-cells with high proliferative potential. Our results indicate that low BUBR1 expression increases oxidative stress-induced mortality in mice, possibly caused by splenic neoplasms. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Dramatic increase in oxidative stress in carbon-irradiated normal human skin fibroblasts.

    PubMed

    Laurent, Carine; Leduc, Alexandre; Pottier, Ivannah; Prévost, Virginie; Sichel, François; Lefaix, Jean-Louis

    2013-01-01

    Skin complications were recently reported after carbon-ion (C-ion) radiation therapy. Oxidative stress is considered an important pathway in the appearance of late skin reactions. We evaluated oxidative stress in normal human skin fibroblasts after carbon-ion vs. X-ray irradiation. Survival curves and radiobiological parameters were calculated. DNA damage was quantified, as were lipid peroxidation (LPO), protein carbonylation and antioxidant enzyme activities. Reduced and oxidized glutathione ratios (GSH/GSSG) were determined. Proinflammatory cytokine secretion in culture supernatants was evaluated. The relative biological effectiveness (RBE) of C-ions vs. X-rays was 4.8 at D₀ (irradiation dose corresponding to a surviving fraction of 37%). Surviving fraction at 2 Gy (SF2) was 71.8% and 7.6% for X-rays and C-ions, respectively. Compared with X-rays, immediate DNA damage was increased less after C-ions, but a late increase was observed at D(10%) (irradiation dose corresponding to a surviving fraction of 10%). LPO products and protein carbonyls were only increased 24 hours after C-ions. After X-rays, superoxide dismutase (SOD) activity was strongly increased immediately and on day 14 at D(0%) (irradiation dose corresponding to a surviving fraction of around 0%), catalase activity was unchanged and glutathione peroxidase (GPx) activity was increased only on day 14. These activities were decreased after C-ions compared with X-rays. GSH/GSSG was unchanged after X-rays but was decreased immediately after C-ion irradiation before an increase from day 7. Secretion of IL-6 was increased at late times after X-ray irradiation. After C-ion irradiation, IL-6 concentration was increased on day 7 but was lower compared with X-rays at later times. C-ion effects on normal human skin fibroblasts seemed to be harmful in comparison with X-rays as they produce late DNA damage, LPO products and protein carbonyls, and as they decrease antioxidant defences. Mechanisms leading to this

  13. Dramatic Increase in Oxidative Stress in Carbon-Irradiated Normal Human Skin Fibroblasts

    PubMed Central

    Laurent, Carine; Leduc, Alexandre; Pottier, Ivannah; Prévost, Virginie; Sichel, François; Lefaix, Jean-Louis

    2013-01-01

    Skin complications were recently reported after carbon-ion (C-ion) radiation therapy. Oxidative stress is considered an important pathway in the appearance of late skin reactions. We evaluated oxidative stress in normal human skin fibroblasts after carbon-ion vs. X-ray irradiation. Survival curves and radiobiological parameters were calculated. DNA damage was quantified, as were lipid peroxidation (LPO), protein carbonylation and antioxidant enzyme activities. Reduced and oxidized glutathione ratios (GSH/GSSG) were determined. Proinflammatory cytokine secretion in culture supernatants was evaluated. The relative biological effectiveness (RBE) of C-ions vs. X-rays was 4.8 at D0 (irradiation dose corresponding to a surviving fraction of 37%). Surviving fraction at 2 Gy (SF2) was 71.8% and 7.6% for X-rays and C-ions, respectively. Compared with X-rays, immediate DNA damage was increased less after C-ions, but a late increase was observed at D10% (irradiation dose corresponding to a surviving fraction of 10%). LPO products and protein carbonyls were only increased 24 hours after C-ions. After X-rays, superoxide dismutase (SOD) activity was strongly increased immediately and on day 14 at D0% (irradiation dose corresponding to a surviving fraction of around 0%), catalase activity was unchanged and glutathione peroxidase (GPx) activity was increased only on day 14. These activities were decreased after C-ions compared with X-rays. GSH/GSSG was unchanged after X-rays but was decreased immediately after C-ion irradiation before an increase from day 7. Secretion of IL-6 was increased at late times after X-ray irradiation. After C-ion irradiation, IL-6 concentration was increased on day 7 but was lower compared with X-rays at later times. C-ion effects on normal human skin fibroblasts seemed to be harmful in comparison with X-rays as they produce late DNA damage, LPO products and protein carbonyls, and as they decrease antioxidant defences. Mechanisms leading to this

  14. Serelaxin Treatment Reduces Oxidative Stress and Increases Aldehyde Dehydrogenase-2 to Attenuate Nitrate Tolerance

    PubMed Central

    Leo, Chen Huei; Fernando, Dhanushke T.; Tran, Lillie; Ng, Hooi Hooi; Marshall, Sarah A.; Parry, Laura J.

    2017-01-01

    Background: Glyceryl trinitrate (GTN) is a commonly prescribed treatment for acute heart failure patients. However, prolonged GTN treatment induces tolerance, largely due to increased oxidative stress and reduced aldehyde dehydrogenase-2 (ALDH-2) expression. Serelaxin has several vasoprotective properties, which include reducing oxidative stress and augmenting endothelial function. We therefore tested the hypothesis in rodents that serelaxin treatment could attenuate low-dose GTN-induced tolerance. Methods and Results: Co-incubation of mouse aortic rings ex vivo with GTN (10 μM) and serelaxin (10 nM) for 1 h, restored GTN responses, suggesting that serelaxin prevented the development of GTN tolerance. Male Wistar rats were subcutaneously infused with ethanol (control), low-dose GTN+placebo or low-dose GTN+serelaxin via osmotic minipumps for 3 days. Aortic vascular function and superoxide levels were assessed using wire myography and lucigenin-enhanced chemiluminescence assay respectively. Changes in aortic ALDH-2 expression were measured by qPCR and Western blot respectively. GTN+placebo infusion significantly increased superoxide levels, decreased ALDH-2 and attenuated GTN-mediated vascular relaxation. Serelaxin co-treatment with GTN significantly enhanced GTN-mediated vascular relaxation, reduced superoxide levels and increased ALDH-2 expression compared to GTN+placebo-treated rats. Conclusion: Our data demonstrate that a combination of serelaxin treatment with low dose GTN attenuates the development of GTN-induced tolerance by reducing superoxide production and increasing ALDH-2 expression in the rat aorta. We suggest that serelaxin may improve nitrate efficacy in a clinical setting. PMID:28377719

  15. Long-term alcohol consumption increases pro-matrix metalloproteinase-9 levels via oxidative stress.

    PubMed

    Koken, Tulay; Gursoy, Fatih; Kahraman, Ahmet

    2010-06-01

    Matrix metalloproteinases (MMPs) play an important role in alcoholic liver disease. In this study, we evaluated the relationship between pro MMP-9 (pMMP-9) and oxidative stress in plasma of rat exposed to chronic alcohol consumption. Twenty four rats were divided into four groups. Rats in the control group (n = 6) were subjected to physiologic saline by intragastric (i.g.) route. Group Ethanol (n = 6) was given 1 ml of 80% ethanol (v/v) in distilled water through i.g. route. Group Vitamin E (Vit E), (n = 6) was given vitamin E (100 mg kg⁻¹ day⁻¹) by intra peritonealy. Group Vitamin E + Ethanol (n = 6) was given vitamin E 2 h before the administration of ethanol. At the end of 4 weeks, blood samples were taken and plasma malondialdehyde (MDA), protein carbonyls (PCs), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and pMMP-9 levels were measured. Chronic ethanol administration increased the AST, MDA, PCs, TNF-α and pMMP-9 levels when compared to those in control group (p < 0.05, p < 0.01, p < 0.01, p < 0.05, p < 0.05, respectively). Vitamin E treatment was found to decrease lipid peroxidation and protein oxidation (p < 0.01, p < 0.01, respectively). Also TNF-α and pMMP-9 levels returned to normal by vitamin E treatment. Within all subjects, there was positive correlation between pMMP-9 levels and MDA, PCs levels (p = 0.045, r = 0.454; p = 0.004, r = 0.574, respectively). We conclude that since antioxidant supplementation decreases the alcohol-induced pMMP-9 levels, oxidative stress could be one of the mediators of the generation of MMP-9.

  16. UCP2 inhibition sensitizes breast cancer cells to therapeutic agents by increasing oxidative stress.

    PubMed

    Pons, Daniel Gabriel; Nadal-Serrano, Mercedes; Torrens-Mas, Margalida; Valle, Adamo; Oliver, Jordi; Roca, Pilar

    2015-09-01

    Modulation of oxidative stress in cancer cells plays an important role in the study of the resistance to anticancer therapies. Uncoupling protein 2 (UCP2) may play a dual role in cancer, acting as a protective mechanism in normal cells, while its overexpression in cancer cells could confer resistance to chemotherapy and a higher survival through downregulation of ROS production. Thus, our aim was to check whether the inhibition of UCP2 expression and function increases oxidative stress and could render breast cancer cells more sensitive to cisplatin (CDDP) or tamoxifen (TAM). For this purpose, we studied clonogenicity, mitochondrial membrane potential (ΔΨm), cell viability, ROS production, apoptosis, and autophagy in MCF-7 and T47D (only the last four determinations) breast cancer cells treated with CDDP or TAM, in combination or without a UCP2 knockdown (siRNA or genipin). Furthermore, survival curves were performed in order to check the impact of UCP2 expression in breast cancer patients. UCP2 inhibition and cytotoxic treatments produced a decrease in cell viability and clonogenicity, in addition to an increase in ΔΨm, ROS production, apoptosis, and autophagy. It is important to note that CDDP decreased UCP2 protein levels, so that the greatest effects produced by the UCP2 inhibition in combination with a cytotoxic treatment, with regard to treatment alone, were observed in TAM+UCP2siRNA-treated cells. Moreover, this UCP2 inhibition caused autophagic cell death, since apoptosis parameters barely increased after UCP2 knockdown. Finally, survival curves revealed that higher UCP2 expression corresponded with a poorer prognosis. In conclusion, UCP2 could be a therapeutic target in breast cancer, especially in those patients treated with tamoxifen. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats

    PubMed Central

    2012-01-01

    Background Higher aluminum (Al) content in infant formula and its effects on neonatal brain development are a cause for concern. This study aimed to evaluate the distribution and concentration of Al in neonatal rat brain following Al treatment, and oxidative stress in brain tissues induced by Al overload. Methods Postnatal day 3 (PND 3) rat pups (n =46) received intraperitoneal injection of aluminum chloride (AlCl3), at dosages of 0, 7, and 35 mg/kg body wt (control, low Al (LA), and high Al (HA), respectively), over 14 d. Results Aluminum concentrations were significantly higher in the hippocampus (751.0 ± 225.8 ng/g v.s. 294.9 ± 180.8 ng/g; p < 0.05), diencephalon (79.6 ± 20.7 ng/g v.s. 20.4 ± 9.6 ng/g; p < 0.05), and cerebellum (144.8 ± 36.2 ng/g v.s. 83.1 ± 15.2 ng/g; p < 0.05) in the HA group compared to the control. The hippocampus, diencephalon, cerebellum, and brain stem of HA animals displayed significantly higher levels of lipid peroxidative products (TBARS) than the same regions in the controls. However, the average superoxide dismutase (SOD) activities in the cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA group compared to the control. The HA animals demonstrated increased catalase activity in the diencephalon, and increased glutathione peroxidase (GPx) activity in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to controls. Conclusion Aluminum overload increases oxidative stress (H2O2) in the hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats. PMID:22613782

  18. The red-vine-leaf extract AS195 increases nitric oxide synthase-dependent nitric oxide generation and decreases oxidative stress in endothelial and red blood cells.

    PubMed

    Grau, Marijke; Bölck, Birgit; Bizjak, Daniel Alexander; Stabenow, Christina Julia Annika; Bloch, Wilhelm

    2016-02-01

    The red-vine-leaf extract AS195 improves cutaneous oxygen supply and the microcirculation in patients suffering from chronic venous insufficiency. Regulation of blood flow was associated to nitric oxide synthase (NOS)-dependent NO (nitric oxide) production, and endothelial and red blood cells (RBC) have been shown to possess respective NOS isoforms. It was hypothesized that AS195 positively affects NOS activation in human umbilical vein endothelial cells (HUVECs) and RBC. Because patients with microvascular disorders show increased oxidative stress which limits NO bioavailability, it was further hypothesized that AS195 increases NO bioavailability by decreasing the content of reactive oxygen species (ROS) and increasing antioxidant capacity. Cultured HUVECs and RBCs from healthy volunteers were incubated with AS195 (100 μmol/L), tert-butylhydroperoxide (TBHP, 1 mmol/L) to induce oxidative stress and with both AS195 and TBHP. Endothelial and red blood cell-nitric oxide synthase (RBC-NOS) activation significantly increased after AS195 incubation. Nitrite concentration, a marker for NO production, increased in HUVEC but decreased in RBC after AS195 application possibly due to nitrite scavenging potential of flavonoids. S-nitrosylation of RBC cytoskeletal spectrins and RBC deformability were increased after AS195 incubation. TBHP-induced ROS were decreased by AS195, and antioxidative capacity was significantly increased in AS195-treated cells. TBHP also reduced RBC deformability, but reduction was attenuated by parallel incubation with AS195. Adhesion of HUVEC was also reduced after AS195 treatment. Red-vine-leaf extract AS195 increases NOS activation and decreases oxidative stress. Both mechanisms increase NO bioavailability, improve cell function, and may thus account for enhanced microcirculation in both health and disease.

  19. Pomegranate juice intake attenuates the increase in oxidative stress induced by intravenous iron during hemodialysis.

    PubMed

    Shema-Didi, Lilach; Kristal, Batya; Ore, Liora; Shapiro, Galina; Geron, Ronit; Sela, Shifra

    2013-06-01

    The hemodialysis (HD) procedure induces oxidative stress (OS), which is further aggravated by intravenous (IV) iron administration, aimed at correcting anemia of patients with HD. We have recently shown that 1 year of pomegranate juice (PJ) intake attenuated OS and inflammation in patients with HD. In the current study, we hypothesized that a single dose of PJ can attenuate the enhanced OS and inflammation induced by both the dialysis procedure and IV iron administration during HD session. Twenty-seven patients with HD were randomized to receive PJ or placebo during 1 dialysis session with IV iron. Blood samples were drawn before and after the session to asses OS biomarkers such as advanced oxidation protein products and myeloperoxidase (MPO), whereas polymorphonuclear leukocyte (PMNL) counts served as an indirect measure of inflammation. At the end of the dialysis session, an increase in advanced oxidation protein products and MPO levels as well as a decrease in PMNLs counts were observed in the placebo group, whereas no significant changes occurred in the PJ group. The postdialysis increase in MPO levels in the placebo group is a direct result of PMNL degranulation, associated with postdialysis decrease in PMNL counts. Degranulation of PMNLs leads to the release of other cell moieties, such as inflammatory mediators and proteases that enhance inflammation. We conclude that PJ intake attenuated the increase in systemic OS and inflammation induced by IV iron administration during the dialysis session. These beneficial effects illuminate the previously observed attenuation in OS and inflammation in patients with HD on prolonged PJ intake.

  20. Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing

    PubMed Central

    Shoghi, Kooresh I.; Silva, Matthew J.

    2013-01-01

    Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), 15O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas 18F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), 15O water and 18F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected. PMID:24356518

  1. Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing.

    PubMed

    Tomlinson, Ryan E; Shoghi, Kooresh I; Silva, Matthew J

    2014-02-15

    Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), (15)O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas (18)F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), (15)O water and (18)F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected.

  2. Colonic motor dysfunction in human diabetes is associated with enteric neuronal loss and increased oxidative stress

    PubMed Central

    Chandrasekharan, Bindu; Anitha, Mallappa; Blatt, Richard; Shahnavaz, Nikrad; Kooby, David; Staley, Charles; Mwangi, Simon; Jones, Dean P; Sitaraman, Shanthi V.; Srinivasan, Shanthi

    2010-01-01

    Background Gastrointestinal dysfunction is very common in diabetic patients. We assessed the changes in the colonic enteric nervous system using colectomy specimens and intestinal biopsies from diabetic subjects and age-matched controls. Methods In control and diabetic colons, we determined the total ganglion area (hematoxylin-eosin staining), changes in neuronal markers-PGP 9.5, peripherin, nNOS, NPY, ChAT and VIP (by immunostaining), apoptosis (cleaved caspase-3 staining) and reduced glutathione levels (HPLC). Superoxide dismutase (SOD) mRNA was determined in enteric ganglia isolated by laser capture micro dissection. Isometric muscle recording was used to assess contraction and relaxation responses of colonic circular muscle strips. Apoptosis in enteric neurons under hyperglycemia in vitro was determined by cleaved caspase-3 Western blotting and protective effects of lipoic acid were evaluated. Key Results Diabetic subjects had higher incidence of lower gastrointestinal symptoms like constipation and diarrhea at baseline prior to surgery. Diabetic ganglia displayed significant decrease in ganglion size due to enhanced apoptosis and loss of peripherin, nNOS, NPY and ChAT neurons. Reduced glutathione levels in the diabetic colon (HbA1C>7%) were significantly less than the control, indicating increased oxidative stress. Colonic circular muscle strips from diabetic subjects showed impaired contraction and relaxation responses compared to the healthy controls. Hyperglycemia-induced cleaved caspase-3 in enteric neurons was reversed by lipoic acid. Conclusions Our data demonstrate loss of enteric neurons in the colon due to increased oxidative stress and apoptosis which may cause the motility disturbances seen in human diabetes. Antioxidants may be of therapeutic value for preventing motility disorders in diabetes. PMID:20939847

  3. Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress.

    PubMed

    Rippe, Catarina; Lesniewski, Lisa; Connell, Melanie; LaRocca, Thomas; Donato, Anthony; Seals, Douglas

    2010-06-01

    To determine if short-term calorie restriction reverses vascular endothelial dysfunction in old mice, old (O, n = 30) and young (Y, n = 10) male B6D2F1 mice were fed ad libitum (AL) or calorie restricted (CR, approximately 30%) for 8 weeks. Ex vivo carotid artery endothelium-dependent dilation (EDD) was impaired in old ad libitum (OAL) vs. young ad libitum (YAL) (74 +/- 5 vs. 95 +/- 2% of maximum dilation, P < 0.05), whereas old calorie-restricted (OCR) and YCR did not differ (96 +/- 1 vs. 94 +/- 3%). Impaired EDD in OAL was mediated by reduced nitric oxide (NO) bioavailability associated with decreased endothelial NO synthase expression (aorta) (P < 0.05), both of which were restored in OCR. Nitrotyrosine, a cellular marker of oxidant modification, was markedly elevated in OAL (P < 0.05), whereas OCR was similar to Y. Aortic superoxide production was 150% greater in OAL vs. YAL (P < 0.05), but normalized in OCR, and TEMPOL, a superoxide dismutase (SOD) mimetic that restored EDD in OAL (to 97 +/- 2%), had no effect in Y or OCR. OAL had increased expression and activity of the oxidant enzyme, NADPH oxidase, and its inhibition (apocynin) improved EDD, whereas NADPH oxidase in OCR was similar to Y. Manganese SOD activity and sirtuin1 expression were reduced in OAL (P < 0.05), but restored to Y in OCR. Inflammatory cytokines were greater in OAL vs. YAL (P < 0.05), but unaffected by CR. Carotid artery endothelium-independent dilation did not differ among groups. Short-term CR initiated in old age reverses age-associated vascular endothelial dysfunction by restoring NO bioavailability, reducing oxidative stress (via reduced NADPH oxidase-mediated superoxide production and stimulation of anti-oxidant enzyme activity), and upregulation of sirtuin-1.

  4. Short-term Calorie Restriction Reverses Vascular Endothelial Dysfunction in Old Mice by Increasing Nitric Oxide and Reducing Oxidative Stress

    PubMed Central

    Rippe, Catarina; Lesniewski, Lisa; Connell, Melanie; LaRocca, Thomas; Donato, Anthony; Seals, Douglas

    2010-01-01

    Summary To determine if short-term calorie restriction reverses vascular endothelial dysfunction in old mice, old (O, n=30) and young (Y, n=10) male B6D2F1 mice were fed ad libitum (AL) or calorie restricted (CR, ∼30%) for 8 weeks. Ex vivo carotid artery endothelium-dependent dilation (EDD) was impaired in OAL vs. YAL (74±5 vs. 95±2% of maximum dilation, P<0.05), whereas OCR and YCR did not differ (96±1 vs. 94±3%). Impaired EDD in OAL was mediated by reduced nitric oxide (NO) bioavailability associated with decreased endothelial NO synthase expression (aorta) (P<0.05), both of which were restored in OCR. Nitrotyrosine, a cellular marker of oxidant modification, was markedly elevated in OAL (P<0.05), whereas OCR was similar to Y. Aortic superoxide production was 150% greater in OAL vs. YAL (P<0.05), but normalized in OCR, and TEMPOL, a superoxide dismutase (SOD) mimetic that restored EDD in OAL (to 97±2%), had no effect in Y or OCR. OAL had increased expression and activity of the oxidant enzyme, NADPH oxidase, and its inhibition (apocynin) improved EDD, whereas NADPH oxidase in OCR was similar to Y. Manganese SOD activity and sirtuin1 expression were reduced in OAL (P<0.05), but restored to Y in OCR. Inflammatory cytokines were greater in OAL vs. YAL (P<0.05), but unaffected by CR. Carotid artery endothelium-independent dilation did not differ among groups. Short-term CR initiated in old age reverses age-associated vascular endothelial dysfunction by restoring NO bioavailability and reducing oxidation stress via reduced NADPH oxidase-mediated superoxide production and stimulation of anti-oxidant enzyme activity, and upregulates sirtuin1. PMID:20121721

  5. Chronic immobilization in the malpar1 knockout mice increases oxidative stress in the hippocampus.

    PubMed

    García-Fernández, María; Castilla-Ortega, Estela; Pedraza, Carmen; Blanco, Eduardo; Hurtado-Guerrero, Isaac; Barbancho, Miguel Angel; Chun, Jerold; Rodríguez-de-Fonseca, Fernando; Estivill-Torrús, Guillermo; Santín Núñez, Luis Javier

    2012-10-01

    The lysophosphatidic acid LPA₁ receptor has recently been involved in the adaptation of the hippocampus to chronic stress. The absence of LPA₁ receptor aggravates the chronic stress-induced impairment of both hippocampal neurogenesis and apoptosis that were accompanied with hippocampus-dependent memory deficits. Apoptotic death and neurogenesis in the hippocampus are regulated by oxidative stress. In the present work, we studied the involvement of LPA₁ receptor signaling pathway in the regulation of the hippocampal redox after chronic stress. To this end, we used malpar1 knockout (KO) and wild-type mice assigned to either chronic stress (21 days of restraint, 3 h/day) or control conditions. Lipid peroxidation, the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX), as well as mitochondrial function stimulation, monitored through the activity of cytochrome c oxidase (COX), were studied in the hippocampus. Our results showed that chronic immobilization stress enhanced lipid peroxidation as well as the activity of the antioxidant enzymes studied (CAT, SOD, and GPX). This effect was only observed in absence of LPA₁ receptor. Furthermore, only malpar1 KO mice submitted to chronic stress exhibited a severe downregulation of the COX activity, suggesting the presence of mitochondrial damage. Altogether, these results suggest that malpar1 KO mice display enhanced oxidative stress in the hippocampus after chronic stress. This may be involved in the hippocampal abnormalities observed in this genotype after chronic immobilization, including memory, neurogenesis, and apoptosis.

  6. Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.

    PubMed

    Correia-Costa, Liane; Sousa, Teresa; Morato, Manuela; Cosme, Dina; Afonso, Joana; Areias, José C; Schaefer, Franz; Guerra, António; Afonso, Alberto C; Azevedo, Ana; Albino-Teixeira, António

    2016-09-01

    Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.

  7. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes

    PubMed Central

    Kwak, Hyo-Bum; Thalacker-Mercer, Anna; Anderson, Ethan J.; Lin, Chien-Te; Kane, Daniel A.; Lee, Nam-Sihk; Cortright, Ronald N.; Bamman, Marcas M.; Neufer, P. Darrell

    2012-01-01

    Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e. myotubes). Simvastatin induced a dose dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose-dependent effect was noted in differentiated myoblasts and myotubes. Additionally, there were decreases in myotube number and size following 48 h of simvastatin treatment (5 µM). In permeabilized myotubes, maximal ADP-stimulated oxygen consumption, supported by palmitoyl-carnitine + malate (PCM, complex I and II substrates) and glutamate + malate (GM, complex I substrates), was 32–37% lower (P<0.05) in simvastatin treated (5 µM) vs. control myotubes, providing evidence of impaired respiration at complex I. Mitochondrial superoxide and hydrogen peroxide generation were significantly greater in the simvastatin treated human skeletal myotube cultures compared to control. In addition, simvastatin markedly increased protein levels of Bax (pro-apoptotic, +53%) and Bcl-2 (anti-apoptotic, +100%, P<0.05), mitochondrial PTP opening (+44%, P<0.05), and TUNEL-positive nuclei in human skeletal myotubes, demonstrating up-regulation of mitochondrial-mediated myonuclear apoptotic mechanisms. These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis in primary human skeletal myotubes, suggesting mitochondrial dysfunction may underlie human statin-induced myopathy. PMID:22080086

  8. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes.

    PubMed

    Kwak, Hyo-Bum; Thalacker-Mercer, Anna; Anderson, Ethan J; Lin, Chien-Te; Kane, Daniel A; Lee, Nam-Sihk; Cortright, Ronald N; Bamman, Marcas M; Neufer, P Darrell

    2012-01-01

    Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e., myotubes). Simvastatin induced a dose-dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose-dependent effect was noted in differentiated myoblasts and myotubes. Additionally, there were decreases in myotube number and size following 48 h of simvastatin treatment (5 μM). In permeabilized myotubes, maximal ADP-stimulated oxygen consumption, supported by palmitoylcarnitine+malate (PCM, complex I and II substrates) and glutamate+malate (GM, complex I substrates), was 32-37% lower (P<0.05) in simvastatin-treated (5 μM) vs control myotubes, providing evidence of impaired respiration at complex I. Mitochondrial superoxide and hydrogen peroxide generation were significantly greater in the simvastatin-treated human skeletal myotube cultures compared to control. In addition, simvastatin markedly increased protein levels of Bax (proapoptotic, +53%) and Bcl-2 (antiapoptotic, +100%, P<0.05), mitochondrial PTP opening (+44%, P<0.05), and TUNEL-positive nuclei in human skeletal myotubes, demonstrating up-regulation of mitochondrial-mediated myonuclear apoptotic mechanisms. These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis in primary human skeletal myotubes, suggesting that mitochondrial dysfunction may underlie human statin-induced myopathy.

  9. Dietary n-3 polyunsaturated fatty acids increase oxidative stress in rats with intracerebral hemorrhagic stroke.

    PubMed

    Park, Yongsoon; Nam, Somyoung; Yi, Hyeong-Joong; Hong, Hyun-Jong; Lee, Myoungsook

    2009-11-01

    Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition-93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA-fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid-reactive substance content was significantly (P < .05) higher in 1% EPA + DHA-fed rats than in 0% and 0.5% EPA + DHA-fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.

  10. Green Tea Increases Insulin Sensitivity and Decreases Brain Oxidative Stress in Fructose Fed Rats

    USDA-ARS?s Scientific Manuscript database

    Hyperglycemia and insulin resistance are leading causes of early brain alterations. Our objective was to investigate the in vivo effects of green tea extract on insulin sensitivity, insulin signaling, and brain oxidative stress using an experimental rodent model of diet-induced insulin resistance, t...

  11. Increased Oxidative Stress Impairs Adipose Tissue Function in Sphingomyelin Synthase 1 Null Mice

    PubMed Central

    Nishimura, Naotaka; Gotoh, Tomomi; Watanabe, Ken; Ikeda, Kazutaka; Garan, Yohei; Taguchi, Ryo; Node, Koichi; Okazaki, Toshiro; Oike, Yuichi

    2013-01-01

    Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we found that SMS1 null mice showed lipodystrophic phenotype. Mutant mice showed up-regulation of plasma triglyceride concentrations accompanied by reduction of white adipose tissue (WAT) as they aged. Lipoprotein lipase (LPL) activity was severely reduced in mutant mice. In vivo analysis indicated that fatty acid uptake in WAT but not in liver decreased in SMS1 null compared to wild-type mice. In vitro analysis using cultured cell revealed that SMS1 depletion reduced fatty acid uptake. Proteins extracted from WAT of mutant mice were severely modified by oxidative stress, and up-regulation of mRNAs related to apoptosis, redox adjustment, mitochondrial stress response and mitochondrial biogenesis was observed. ATP content of WAT was reduced in SMS1 null mice. Blue native gel analysis indicated that accumulation of mitochondrial respiratory chain complexes was reduced. These results suggest that WAT of SMS1 null mice is severely damaged by oxidative stress and barely functional. Indeed, mutant mice treated with the anti-oxidant N-acetyl cysteine (NAC) showed partial recovery of lipodystrophic phenotypes together with normalized plasma triglyceride concentrations. Altogether, our data suggest that SMS1 is crucial to control oxidative stress in order to maintain WAT function. PMID:23593476

  12. A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress.

    PubMed

    Arkblad, Eva L; Tuck, Simon; Pestov, Nikolay B; Dmitriev, Ruslan I; Kostina, Maria B; Stenvall, Jörgen; Tranberg, Mattias; Rydström, Jan

    2005-06-01

    Proton-translocating mitochondrial nicotinamide nucleotide transhydrogenase (NNT) was investigated regarding its physiological role in Caenorhabditis elegans. NNT catalyzes the reduction of NADP(+) by NADH driven by the electrochemical proton gradient, Deltap, and is thus a potentially important source of mitochondrial NADPH. Mitochondrial detoxification of reactive oxygen species (ROS) by glutathione-dependent peroxidases depends on NADPH for regeneration of reduced glutathione. Transhydrogenase may therefore be directly involved in the defense against oxidative stress. nnt-1 deletion mutants of C. elegans, nnt-1(sv34), were isolated and shown to grow essentially as wild type under normal laboratory conditions, but with a strongly lowered GSH/GSSG ratio. Under conditions of oxidative stress, caused by the superoxide-generating agent methyl viologen, growth of worms lacking nnt-1 activity was severely impaired. A similar result was obtained by using RNAi. Reintroducing nnt-1 in the nnt-1(sv34) knockout mutant led to a partial rescue of growth under oxidative stress conditions. These results provide evidence for the first time that nnt-1 is important in the defense against mitochondrial oxidative stress.

  13. Taurine increases testicular function in aged rats by inhibiting oxidative stress and apoptosis.

    PubMed

    Yang, Jiancheng; Zong, Xiaomeng; Wu, Gaofeng; Lin, Shumei; Feng, Ying; Hu, Jianmin

    2015-08-01

    In males, the decline of androgen synthesis, spermatogenesis and sexual function are the main phenotypes of aging, which may be attributed to testicular dysfunction. Taurine can act as an antioxidant, a testosterone secretion stimulator, a sperm membrane stabilizer and motility factor, and an anti-apoptotic agent. Recent observational studies suggested that taurine may play an important role in spermatogenesis, but to date whether taurine has anti-aging effects on testes remains unknown. We found that in aged rats testicular SDH and G6PDH activities, marker enzymes of testes, serum testosterone, testicular 3β-HSD and 17β-HSD mRNA expression levels were significantly increased by taurine treatment. Taurine administration also markedly raised the sperm count, viability and motility, decreased the sperm abnormality. Our data suggested that taurine can postpone testicular function deterioration in aged rats. Importantly, we observed obvious elevation of testicular antioxidant enzymes (SOD, GSH, GSH-Px) activities, and remarkable reduction of ROS and MDA by taurine administration, indicating taurine can decrease testicular oxidative stress and lipid peroxidation in aged rats. Finally, we found taurine effectively reduced testicular DNA fragmentation, increased testicular Bcl-2 protein expression, and decreased cytochrome c, Bax, Fas, FasL and caspase-3 expression, suggesting taurine can prohibit aged testicular apoptosis by mitochondrial dependent and independent signal pathway. In summary, our results indicated that taurine can suppress testicular function deterioration by increasing antioxidant ability and inhibiting apoptosis.

  14. Exercise Increases Cystathionine-γ-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats.

    PubMed

    Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Lu, Jianqiang

    2016-01-01

    Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling.

  15. Penicillamine Increases Free Copper and Enhances Oxidative Stress in the Brain of Toxic Milk Mice

    PubMed Central

    Lin, Xiao-Pu; Zhang, Wei; Li, Fu-Rong; Liang, Xiu-Ling; Li, Xun-Hua

    2012-01-01

    Wilson disease (WD) is characterized by the accumulation of copper arising from a mutation in the ATP7B gene. Penicillamine (PA) makes 10–50% of the patients with neurologic symptoms neurologically worse at the early stage of administration. The aim of this study was to determine how the copper metabolism changes and whether the change impairs the brain of toxic milk (tx) mice, an animal model of WD, during the PA administration. The free copper and protein-bound copper concentrations in the serum, cortex and basal ganglia of tx mice with PA administration for 3 days, 10 days and 14 days, respectively, were investigated. The expression of copper transporters, ATP7A and CTR1,was analyzed by real-time quantitative PCR, immunofluorescence and Western blot. Then SOD, MDA and GSH/GSSG were detected to determine whether the oxidative stress changed correspondingly. The results revealed the elevated free copper concentrations in the serum and brain, and declined protein-bound copper concentrations in the brain of tx mice during PA administration. Meanwhile, transiently increased expression of ATP7A and CTR1 was observed generally in the brain parenchyma by immunofluorescence, real-time quantitative PCR and Western blot. Additionally, ATP7A and CTR1 were observed to locate mainly at Golgi apparatus and cellular membrane respectively. Intense staining of ATP7A in the choroid plexus was found in tx mice on the 3rd and 10th day of PA treatment, but rare staining of ATP7A and CTR1 in the blood-brain barrier (BBB). Decreased GSH/GSSG and increased MDA concentrations were also viewed in the cortex and basal ganglia. Our results suggested the elevated free copper concentrations in the brain might lead to the enhanced oxidative stress during PA administration. The increased free copper in the brain might come from the copper mobilized from brain parenchyma cells but not from the serum according to the ATP7A and CTR1 expression analysis. PMID:22629446

  16. Nanomolar concentrations of zinc pyrithione increase cell susceptibility to oxidative stress induced by hydrogen peroxide in rat thymocytes.

    PubMed

    Oyama, Tomohiro M; Saito, Minoru; Yonezawa, Takayasu; Okano, Yoshiro; Oyama, Yasuo

    2012-06-01

    Zinc pyrithione is used as an antifouling agent. However, the environmental impacts of zinc pyrithione have recently been of concern. Zinc induces diverse actions during oxidative stress; therefore, we examined the effect of zinc pyrithione on rat thymocytes suffering from oxidative stress using appropriate fluorescent probes. The cytotoxicity of zinc pyrithione was not observed when the cells were incubated with 3 μM zinc pyrithione for 3 h. However, zinc pyrithione at nanomolar concentrations (10 nM or more) significantly increased the lethality of cells suffering from oxidative stress induced by 3 mM H(2)O(2). The application of zinc pyrithione alone at nanomolar concentrations increased intracellular Zn(2+) level and the cellular content of superoxide anions, and decreased the cellular content of nonprotein thiols. The simultaneous application of nanomolar zinc pyrithione and micromolar H(2)O(2) synergistically increased the intracellular Zn(2+) level. Therefore, zinc pyrithione at nanomolar concentrations may exert severe cytotoxic action on cells simultaneously exposed to chemicals that induce oxidative stress. If so, zinc pyrithione leaked from antifouling materials into surrounding environments would be a risk factor for aquatic ecosystems. Alternatively, zinc pyrithione under conditions of oxidative stress may become more potent antifouling ingredient.

  17. Possible role of increased oxidative stress in pulmonary hypertension in experimental diaphragmatic hernia.

    PubMed

    Aras-López, R; Tovar, J A; Martínez, L

    2016-02-01

    Congenital diaphragmatic hernia (CDH) is one of the causes of respiratory failure in newborns due to lung hypoplasia and pulmonary abnormalities leading to pulmonary hypertension (PH). NAD(P)H oxidase (Nox) is a family of isoenzymes that generate reactive oxygen species (ROS) which can contribute to PH-induced vascular dysfunction. On the other hand, superoxide dismutase (SOD) 1-2 and catalase are the antioxidant enzymes that eliminate the excess of ROS in pulmonary vascular cells. Our aim is to examine whether PH-associated with CDH is due to a dysregulation of ROS production in lungs from CDH fetuses. Pregnant rats received either 100 mg nitrofen or vehicle on E9.5. Fetuses were recovered on E21. (1) Nox activity, (2) H2O2 production and (3) mRNA levels of Nox1, Nox2, Nox4, SOD1, SOD2 and catalase were analyzed in fetal lungs. Nox activity and Nox1 and Nox2 mRNA levels were increased in the lungs of fetuses with CDH. However, there were no changes in H2O2 production and Nox4 mRNA levels. SOD1, SOD2 and catalase were decreased. The raised oxidative stress due to increase in ROS generation by Nox isoenzymes and dysfunction of antioxidant enzymes seems to be a potential mechanism responsible on PH-associated with CDH.

  18. Higher serum iron is associated with increased oxidant stress in HIV-infected men

    PubMed Central

    Crist, Matthew B.; Melekhin, Vlada V.; Bian, Aihua; Shintani, Ayumi; Milne, Ginger L.; Kallianpur, Asha R.; Dageforde, Leigh Anne; Haas, David W.; Hulgan, Todd

    2013-01-01

    Background F2-isoprostanes (F2-IsoP) are oxidant stress biomarkers that are higher in HIV-infected women than men. We explored whether the effect of hemoglobin (Hgb), serum iron, or anemia on F2-IsoP is different between HIV-infected women and men. Methods Plasma F2-IsoP were quantified by gas chromatography/mass spectrometry; clinical and laboratory data were collected at enrollment or from the medical record. Multivariable linear regression was used to assess associations between F2-IsoP and Hgb, anemia as a dichotomous variable, and serum iron with adjustment for age, sex, race, body-mass index, CD4+ lymphocyte count, self-reported current smoking status, and antiretroviral therapy. Results Compared to men, women had lower Hgb (median [IQR] 12.7 [11.8-13.9] vs. 14.9 [13.7-15.8] g/dL, P<0.001), lower iron levels (75 [47-97] vs. 90 [69-121] μg/dL, P=0.004), more anemia (29% vs. 10%, P<0.001), and higher levels of F2-IsoP (42 [32-62] vs. 36 [25-46] pg/mL, P<0.001). The relationship between iron and F2-IsoP differed significantly between men and women (interaction P=0.02). Men had a 21% (95% CI: 8%-36%) increase in F2-IsoP per interquartile increase in iron (P=0.001); while no relationship was seen among women (-4% [-17%-13%], P=0.65). Conclusions Although women have overall higher F2-IsoP than men, a relationship between circulating F2-IsoP and iron levels was observed in men but not in women with HIV infection. The association between female sex and higher F2-IsoP is not explained by iron or Hgb levels as the association persists when controlling for these factors. The role of iron in oxidant stress and sex-specific differences among HIV-infected individuals require further study. PMID:24169121

  19. Pretreatment of the yeast antagonist, Candida oleophila, with glycine betaine increases oxidative stress tolerance in the microenvironment of apple wounds.

    PubMed

    Sui, Yuan; Liu, Jia; Wisniewski, Michael; Droby, Samir; Norelli, John; Hershkovitz, Vera

    2012-06-15

    In response to wounding, harvested fruit tissues of apple and citrus exhibit the production of reactive oxygen species (ROS). ROS production is greater when yeast antagonists used as biocontrol agents are applied in the wounds. These phenomena result in an oxidative stress environment for the yeast antagonists. It has been demonstrated that pre-exposure of some of these yeast antagonists to sublethal abiotic stress (heat or hydrogen peroxide), or stress-ameliorating compounds such as glycine betaine (GB) can induce subsequent oxidative stress tolerance in the antagonistic yeast. The increased level of oxidative stress tolerance has been demonstrated in vitro and is characterized by higher levels of antioxidant gene expression, increased production of trehalose, and lower levels of ROS when yeast are exposed to a subsequent oxidative stress. The current study determined whether or not the effects of GB on yeast antagonists determined in vitro persist and are present in planta when yeast are applied to wounded apples. The effect of exogenous GB on the production of ROS in the yeast antagonist, Candida oleophila, was determined after the yeast was placed in apple wounds. Oxidative damage to yeast cells recovered from apple wounds was also monitored. Results indicated that GB treatment improved the adaptation of C. oleophila to apple fruit wounds. Compared to untreated control yeast cells, GB-treated cells recovered from the oxidative stress environment of apple wounds exhibited less accumulation of ROS and lower levels of oxidative damage to cellular proteins and lipids. Additionally, GB-treated yeast exhibited greater biocontrol activity against Penicillium expansum and Botrytis cinerea, and faster growth in wounds of apple fruits compared to untreated yeast. The expression of major antioxidant genes, including peroxisomal catalase, peroxiredoxin TSA1, and glutathione peroxidase was elevated in the yeast by GB treatment. This study supports the premise that

  20. Mitochondrial Dysfunction Increases Oxidative Stress and Decreases Chronological Life Span in Fission Yeast

    PubMed Central

    García-Santamarina, Sarela; Hoe, Kwang-Lae; Kim, Dong Uk; Park, Han-Oh; Hayles, Jacqueline; Ayté, José; Hidalgo, Elena

    2008-01-01

    Background Oxidative stress is a probable cause of aging and associated diseases. Reactive oxygen species (ROS) originate mainly from endogenous sources, namely the mitochondria. Methodology/Principal Findings We analyzed the effect of aerobic metabolism on oxidative damage in Schizosaccharomyces pombe by global mapping of those genes that are required for growth on both respiratory-proficient media and hydrogen-peroxide-containing fermentable media. Out of a collection of approximately 2700 haploid yeast deletion mutants, 51 were sensitive to both conditions and 19 of these were related to mitochondrial function. Twelve deletion mutants lacked components of the electron transport chain. The growth defects of these mutants can be alleviated by the addition of antioxidants, which points to intrinsic oxidative stress as the origin of the phenotypes observed. These respiration-deficient mutants display elevated steady-state levels of ROS, probably due to enhanced electron leakage from their defective transport chains, which compromises the viability of chronologically-aged cells. Conclusion/Significance Individual mitochondrial dysfunctions have often been described as the cause of diseases or aging, and our global characterization emphasizes the primacy of oxidative stress in the etiology of such processes. PMID:18665268

  1. Increased Electron Paramagnetic Resonance Signal Correlates with Mitochondrial Dysfunction and Oxidative Stress in an Alzheimer’s Disease Mouse Brain

    PubMed Central

    Fang, Du; Zhang, Zhihua; Li, Hang; Yu, Qing; Douglas, Justin T.; Bratasz, Anna; Kuppusamy, Periannan; Yan, Shirley ShiDu

    2016-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized clinically by cognitive decline and memory loss. The pathological features are amyloid-β peptide (Aβ) plaques and intracellular neurofibrillary tangles. Many studies have suggested that oxidative damage induced by reactive oxygen species (ROS) is an important mechanism for AD progression. Our recent study demonstrated that oxidative stress could further impair mitochondrial function. In the present study, we adopted a transgenic mouse model of AD (mAPP, overexpressing AβPP/Aβ in neurons) and performed redox measurements using in vivo electron paramagnetic resonance (EPR) imaging with methoxycarbamyl-proxyl (MCP) as a redox-sensitive probe for studying oxidative stress in an early stage of pathology in a transgenic AD mouse model. Through assessing oxidative stress, mitochondrial function and cognitive behaviors of mAPP mice at the age of 8–9 months, we found that oxidative stress and mitochondrial dysfunction appeared in the early onset of AD. Increased ROS levels were associated with defects of mitochondrial and cognitive dysfunction. Notably, the in vivo EPR method offers a unique way of assessing tissue oxidative stress in living animals under noninvasive conditions, and thus holds a potential for early diagnosis and monitoring the progression of AD. PMID:26890765

  2. Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers

    DTIC Science & Technology

    2014-08-01

    permeability and integrity of the brain endothelium using in vitro and in vivo models. 3) Determine the protective effects of PARP inhibitors and/or selenium ...in preventing BBB-induced damage by oxidative stress, and in inhibiting breast cancer metastasis to the brain. Further, since selenium has anti...inhibitor and ROS inhibitor of BMEC-TJs HBMEC cocultures were preincubated with PARP inhibitor (30mM) or with ROS inhibitor (10mM selenium ) for 6

  3. Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes

    PubMed Central

    Noh, Y H; Kim, K-Y; Shim, M S; Choi, S-H; Choi, S; Ellisman, M H; Weinreb, R N; Perkins, G A; Ju, W-K

    2013-01-01

    Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells against oxidative stress in many neurodegenerative diseases. Here, we tested whether hydrogen peroxide (100 μM H2O2)-induced oxidative stress alters the mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression and bioenergetics, as well as whether CoQ10 can ameliorate oxidative stress-mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative stress triggered the activation of ONH astrocytes and the upregulation of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in the ONH astrocytes. In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress. Further, CoQ10 prevented a significant loss of mitochondrial mass by increasing mitochondrial number and volume density and by preserving mitochondrial cristae structure, as well as promoted mitofilin and peroxisome-proliferator-activated receptor-γ coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes. However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes. On the basis of these observations, we suggest that oxidative stress-mediated mitochondrial dysfunction or alteration may be an important

  4. Prolonged exposure to insulin induces mitochondrion-derived oxidative stress through increasing mitochondrial cholesterol content in hepatocytes.

    PubMed

    Mei, Shuang; Gu, Haihua; Yang, Xuefeng; Guo, Huailan; Liu, Zhenqi; Cao, Wenhong

    2012-05-01

    We addressed the link between excessive exposure to insulin and mitochondrion-derived oxidative stress in this study and found that prolonged exposure to insulin increased mitochondrial cholesterol in cultured hepatocytes and in mice and stimulated production of reactive oxygen species (ROS) and decreased the reduced glutathione to glutathione disulfide ratio in cultured hepatocytes. Exposure of isolated hepatic mitochondria to cholesterol alone promoted ROS emission. The oxidative stress induced by the prolonged exposure to insulin was prevented by inhibition of cholesterol synthesis with simvastatin. We further found that prolonged exposure to insulin decreased mitochondrial membrane potential and the increased ROS production came from mitochondrial respiration complex I. Finally, we observed that prolonged exposure to insulin decreased mitochondrial membrane fluidity in a cholesterol synthesis-dependent manner. Together our results demonstrate that excess exposure to insulin causes mitochondrion-derived oxidative stress through cholesterol synthesis in hepatocytes.

  5. Aerobic condition increases carotenoid production associated with oxidative stress tolerance in Enterococcus gilvus.

    PubMed

    Hagi, Tatsuro; Kobayashi, Miho; Nomura, Masaru

    2014-01-01

    Although it is known that a part of lactic acid bacteria can produce carotenoid, little is known about the regulation of carotenoid production. The objective of this study was to determine whether aerobic growth condition influences carotenoid production in carotenoid-producing Enterococcus gilvus. Enterococcus gilvus was grown under aerobic and anaerobic conditions. Its growth was slower under aerobic than under anaerobic conditions. The decrease in pH levels and production of lactic acid were also lower under aerobic than under anaerobic conditions. In contrast, the amount of carotenoid pigments produced by E. gilvus was significantly higher under aerobic than under anaerobic conditions. Further, real-time quantitative reverse transcription PCR revealed that the expression level of carotenoid biosynthesis genes crtN and crtM when E. gilvus was grown under aerobic conditions was 2.55-5.86-fold higher than when it was grown under anaerobic conditions. Moreover, after exposure to 16- and 32-mM H2O2, the survival rate of E. gilvus grown under aerobic conditions was 61.5- and 72.5-fold higher, respectively, than when it was grown under anaerobic conditions. Aerobic growth conditions significantly induced carotenoid production and the expression of carotenoid biosynthesis genes in E. gilvus, resulting in increased oxidative stress tolerance.

  6. Maternal obesity and overnutrition increase oxidative stress in male rat offspring reproductive system and decrease fertility.

    PubMed

    Rodríguez-González, G L; Vega, C C; Boeck, L; Vázquez, M; Bautista, C J; Reyes-Castro, L A; Saldaña, O; Lovera, D; Nathanielsz, P W; Zambrano, E

    2015-04-01

    Increasing evidence exists that maternal obesity (MO) and overnutrition during pregnancy and lactation have long-lasting consequences for progeny metabolism, cardiovascular and endocrine function. Data on effects of MO on offspring reproduction are limited. We hypothesized that MO during pregnancy and lactation in founder F(0) rat mothers would increase testicular and sperm oxidative stress (OS) and adversely impact male fertility in their F(1) offspring. We induced pre-pregnancy MO by feeding F(0) females a high-fat diet from weaning through pregnancy and lactation. After weaning, all F(1) rats ate control (C) diet. We determined serum testosterone, malondialdehyde (MDA), reactive oxygen species (ROS) and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in F(1) testes and sperm at postnatal days (PNDs) 110, 450 and 650. At PNDs 450 and 650, MO offspring had lower luteinizing hormone while testosterone levels were lower at all ages. Testicular MDA and ROS concentrations and SOD and GPx activity were higher in MO F(1) at all ages. Nitrotyrosine immunostaining was higher at all ages in MO F(1) testes than C F(1). At PNDs 450 and 650, MO F(1) spermatozoa showed higher MDA concentrations and lower SOD and GPx activity with reduced sperm concentration, viability and motility, and more sperm abnormalities. Fertility rate was not affected at PND 110 but was lower in MO F(1) at PNDs 450 and 650. We conclude that MO during pregnancy and lactation increases F(1) testicular and sperm OS leading to premature aging of reproductive capacity.

  7. Experimental Priapism is Associated with Increased Oxidative Stress and Activation of Protein Degradation Pathways in Corporal Tissue

    PubMed Central

    Kanika, Nirmala D.; Melman, Arnold; Davies, Kelvin P.

    2010-01-01

    Priapism is a debilitating disease for which there is at present no clinically accepted pharmacologic intervention. It has been estimated that priapism lasting more than 24 hours in patients is associated with a 44–90% rate of erectile dysfunction (ED). In this investigation we determined in two animal models of priapism (opiorpin-induced priapism in the rat and priapism in a mouse model of sickle cell disease) if there is evidence for an increase in markers of oxidative stress in corporal tissue. In both animal models we demonstrate that priapism results in increased levels of lipid peroxidation, glutathione S-transferase activity, and oxidatively damaged proteins in corporal tissue. Using Western blot analysis we demonstrated there is up regulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysososomal autophage protein, LC3. The anti-apoptotic protein, Bcl-2, was also up regulated. Overall, we demonstrate that priapism is associated with increased oxidative stress in corporal tissue and the activation of protein degradation pathways. Since oxidative stress is known to mediate the development of ED resulting from several etiologies (for example ED resulting from diabetes and aging) we suggest that damage to erectile tissue resulting from priapism might be prevented by treatments targeting oxidative stress. PMID:21085184

  8. Experimental priapism is associated with increased oxidative stress and activation of protein degradation pathways in corporal tissue.

    PubMed

    Kanika, N D; Melman, A; Davies, K P

    2010-01-01

    Priapism is a debilitating disease for which there is at present no clinically accepted pharmacological intervention. It has been estimated that priapism lasting more than 24 h in patients is associated with a 44-90% rate of ED. In this investigation, we determined in two animal models of priapism (opiorphin-induced priapism in the rat and priapism in a mouse model of sickle cell disease) if there is evidence for an increase in markers of oxidative stress in corporal tissue. In both animal models, we demonstrate that priapism results in increased levels of lipid peroxidation, glutathione S-transferase activity and oxidatively damaged proteins in corporal tissue. Using western blot analysis, we demonstrated there is upregulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysosomal autophage protein, LC3. The antiapoptotic protein, Bcl-2, was also upregulated. Overall, we demonstrate that priapism is associated with increased oxidative stress in corporal tissue and the activation of protein degradation pathways. As oxidative stress is known to mediate the development of ED resulting from several etiologies (for example, ED resulting from diabetes and aging), we suggest that damage to erectile tissue resulting from priapism might be prevented by treatments targeting oxidative stress.

  9. C-Terminus of Heat Shock Cognate 70 Interacting Protein Increases Following Stroke and Impairs Survival Against Acute Oxidative Stress

    PubMed Central

    Stankowski, Jeannette N.; Zeiger, Stephanie L.H.; Cohen, Evan L.; DeFranco, Donald B.; Cai, Jiyang

    2011-01-01

    Abstract The decision to remove or refold oxidized, denatured, or misfolded proteins by heat shock protein 70 and its binding partners is critical to determine cell fate under pathophysiological conditions. Overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other ubiquitin ligases and enhance protein turnover and survival under chronic neurological stress. The ability of CHIP to alter cell fate after acute neurological injury has not been assessed. Using postmortem human tissue samples, we provide the first evidence that cortical CHIP expression is increased after ischemic stroke. Oxygen glucose deprivation in vitro led to rapid protein oxidation, antioxidant depletion, proteasome dysfunction, and a significant increase in CHIP expression. To determine if CHIP upregulation enhances neural survival, we overexpressed CHIP in vitro and evaluated cell fate 24 h after acute oxidative stress. Surprisingly, CHIP overexpressing cells fared worse against oxidative injury, accumulated more ubiquitinated and oxidized proteins, and experienced decreased proteasome activity. Conversely, using small interfering RNA to decrease CHIP expression in primary neuronal cultures improved survival after oxidative stress, suggesting that increases in CHIP observed after stroke like injuries are likely correlated with diminished survival and may negatively impact the neuroprotective potential of heat shock protein 70. Antioxid. Redox Signal. 14, 1787–1801. PMID:20677910

  10. Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

    PubMed Central

    Ceretta, Luciane B.; Réus, Gislaine Z.; Abelaira, Helena M.; Ribeiro, Karine F.; Zappellini, Giovanni; Felisbino, Francine F.; Steckert, Amanda V.; Dal-Pizzol, Felipe; Quevedo, João

    2012-01-01

    Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (SNC) as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg), and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS) production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals' recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes. PMID:22645603

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

    SciTech Connect

    Kippler, Maria; Bakhtiar Hossain, Mohammad; Lindh, Christian; Moore, Sophie E.; Kabir, Iqbal; Vahter, Marie; Broberg, Karin

    2012-01-15

    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-oxodG 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.

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

    PubMed

    Kippler, Maria; Hossain, Mohammad Bakhtiar; Lindh, Christian; Moore, Sophie E; Kabir, Iqbal; Vahter, Marie; Broberg, Karin

    2012-01-01

    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'-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-oxodG was 3.9 nmol/L, urinary Cd 0.30 μg/L, and breast-milk Cd 0.13 μg/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. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Effect of increasing body condition on oxidative stress and mitochondrial biogenesis in subcutaneous adipose tissue depot of nonlactating dairy cows.

    PubMed

    Laubenthal, L; Ruda, L; Sultana, N; Winkler, J; Rehage, J; Meyer, U; Dänicke, S; Sauerwein, H; Häussler, S

    2017-06-01

    With the onset of lactation, dairy cows with a body condition score >3.5 are sensitive to oxidative stress and metabolic disorders. Adipose tissue (AT) can adapt to varying metabolic demands and energy requirements by the plasticity of its size during lactation. In AT, angiogenesis is necessary to guarantee sufficient oxygen and nutrient supply for adipocytes. Cellular energy metabolism is reflected mainly by mitochondria, which can be quantified by the mitochondrial DNA copy number per cell. In the present study, we aimed to investigate the effect of overconditioning on angiogenesis and mitochondrial biogenesis in AT of nonlactating cows, irrespective of the physiological influences of lactation and pregnancy. Eight nonpregnant, nonlactating cows received a ration of increasing energy density for 15 wk, during which body weight and body condition increased substantially. Subcutaneous AT was biopsied every 8 wk, and blood was sampled monthly. The blood concentrations of indicators of oxidative stress increased continuously throughout the experimental period, possibly damaging mitochondrial DNA. Concomitantly, HIF-1α, a major marker for hypoxia, increased until wk 8, indicating insufficient angiogenesis in the rapidly expanding AT. Based on the observation that the number of apoptotic cells decreased with increasing hypoxia, the increasing mitochondrial DNA copy numbers might compensate for the hypoxia, reinforcing the production of oxidative stressors. Key transcription factors of mitochondrial biogenesis were largely unaffected. Thus, increased oxidative stress does not impair mitochondrial DNA. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Increased expression of endothelial and neuronal nitric oxide synthase in dura and pia mater after air stress.

    PubMed

    Zinck, T; Illum, R; Jansen-Olesen, I

    2006-01-01

    Stress is the leading precipitating factor for migraine attacks but the underlying mechanism is currently unknown. Nitric oxide (NO) has been implicated in migraine pathogenesis based on the ability of NO donors to induce migraine attacks. In the present study, we investigated in Wistar rats the effect of air stress on nitric oxide synthase (NOS) mRNA and protein expression in dura and pia mater using real-time polymerase chain reaction and Western blotting, respectively. Endothelial (e)NOS protein expression was significantly increased in dura and pia mater after air stress. Significantly augmented neuronal (n)NOS protein expression was detected in pia mater after air stress but not in dura mater. Inducible NOS mRNA and protein expression levels in dura and pia mater were unaffected by stress. The increased expression of eNOS in dura mater and eNOS and nNOS in pia mater seen after stress could not be antagonized by treatment with the migraine drug sumatriptan. These findings point towards the involvement of increased NO concentrations in dura and pia mater in response to air stress. However, the role of these findings in relation to migraine pathophysiology remains unclear.

  15. Environmental Stresses Increase Photosynthetic Disruption by Metal Oxide Nanomaterials in a Soil-Grown Plant.

    PubMed

    Conway, Jon R; Beaulieu, Arielle L; Beaulieu, Nicole L; Mazer, Susan J; Keller, Arturo A

    2015-12-22

    Despite an increasing number of studies over the past decade examining the interactions between plants and engineered nanomaterials (ENMs), very few have investigated the influence of environmental conditions on ENM uptake and toxicity, particularly throughout the entire plant life cycle. In this study, soil-grown herbaceous annual plants (Clarkia unguiculata) were exposed to TiO2, CeO2, or Cu(OH)2 ENMs at different concentrations under distinct light and nutrient levels for 8 weeks. Biweekly fluorescence and gas exchange measurements were recorded, and tissue samples from mature plants were analyzed for metal content. During peak growth, exposure to TiO2 and CeO2 decreased photosynthetic rate and CO2 assimilation efficiency of plants grown under high light and nutrient conditions, possibly by disrupting energy transfer from photosystem II (PSII) to the Calvin cycle. Exposure Cu(OH)2 particles also disrupted photosynthesis but only in plants grown under the most stressful conditions (high light, limited nutrient) likely by preventing the oxidation of a primary PSII reaction center. TiO2 and CeO2 followed similar uptake and distribution patterns with concentrations being highest in roots followed by leaves then stems, while Cu(OH)2 was present at highest concentrations in leaves, likely as ionic Cu. ENM accumulation was highly dependent on both light and nutrient levels and a predictive regression model was developed from these data. These results show that abiotic conditions play an important role in mediating the uptake and physiological impacts of ENMs in terrestrial plants.

  16. Mitochondrial oxidative stress-induced hepatocyte apoptosis reflects increased molybdenum intake in caprine.

    PubMed

    Zhuang, Yu; Liu, Ping; Wang, Liqi; Luo, Junrong; Zhang, Caiying; Guo, Xiaoquan; Hu, Guoliang; Cao, Huabin

    2016-03-01

    Molybdenum (Mo) is an essential trace element for animals and humans. However, the high dietary intake of Mo leads to disease conditions in heavy metal pollution areas. To the best of our knowledge, the effect of high levels of Mo on the apoptosis of hepatocyte in goats has not been investigated. Therefore, the aim of the present in vivo study was to investigate the impact of Mo on mitochondrial oxidative stress and apoptosis genes in the liver using real-time quantitative polymerase chain reaction (RT-qPCR) and transmission electron microscopy, respectively. Thirty-six healthy goats were randomly divided into three groups: two groups treated with ammonium molybdate [(NH4)6·Mo7O24·H2O] at 15 and 45 mg Mo kg(-1) BW, respectively, and a control group without treatment. Liver samples were collected from individual goats at different time intervals. The levels of oxidative stress in the mitochondrial membrane and expression of liver-related apoptosis genes, including Bcl-2, Cyt c, caspase-3, and Smac, were examined. The results demonstrated that the levels of superoxide dismutase (SOD) and catalase (CAT) expression were significantly down-regulated in liver cells, whereas malondialdehyde (MDA), nitric oxide (NO), and total nitric oxide synthase (T-NOS) expression was up-regulated (P < 0.01). The expression of Smac, Cyt c, and caspase-3 was significantly up-regulated, whereas Bcl-2 expression was down-regulated in liver cells (P < 0.01). In addition, histopathological examination revealed varying degrees of vacuolization, irregularity, nuclear fission, and mitochondrial swelling and high-density electrons in the cytoplasm of hepatocytes in groups treated with 15 and 45 mg Mo kg(-1) BW. Thus, these results suggested that high molybdenum induced hepatocyte apoptosis and might involve a mitochondrial pathway.

  17. Increased renal oxidative stress in salt-sensitive human GRK4γ486V transgenic mice.

    PubMed

    Diao, Zhenyu; Asico, Laureano D; Villar, Van Anthony M; Zheng, Xiaoxu; Cuevas, Santiago; Armando, Ines; Jose, Pedro A; Wang, Xiaoyan

    2017-05-01

    We tested the hypothesis that salt-sensitive hypertension is caused by renal oxidative stress by measuring the blood pressure and reactive oxygen species-related proteins in the kidneys of human G protein-coupled receptor kinase 4γ (hGRK4γ) 486V transgenic mice and non-transgenic (Non-T) littermates on normal and high salt diets. High salt diet increased the blood pressure, associated with impaired sodium excretion, in hGRK4γ486V mice. Renal expressions of NOX isoforms were similar in both strains on normal salt diet but NOX2 was decreased by high salt diet to a greater extent in Non-T than hGRK4γ486V mice. Renal HO-2, but not HO-1, protein was greater in hGRK4γ486V than Non-T mice on normal salt diet and normalized by high salt diet. On normal salt diet, renal CuZnSOD and ECSOD proteins were similar but renal MnSOD was lower in hGRK4γ486V than Non-T mice and remained low on high salt diet. High salt diet decreased renal CuZnSOD in hGRK4γ486V but not Non-T mice and decreased renal ECSOD to a greater extent in hGRK4γ486V than Non-T mice. Renal SOD activity, superoxide production, and NOS3 protein were similar in two strains on normal salt diet. However, high salt diet decreased SOD activity and NOS3 protein and increased superoxide production in hGRK4γ486V mice but not in Non-T mice. High salt diet also increased urinary 8-isoprostane and 8-hydroxydeoxyguanosine to a greater extent in hGRK4γ486V than Non-T mice. hGRK4γwild-type mice were normotensive and hGRK4γ142V mice were hypertensive but both were salt-resistant and in normal redox balance. Chronic tempol treatment partially prevented the salt-sensitivity of hGRK4γ486V mice. Thus, hGRK4γ486V causes salt-sensitive hypertension due, in part, to defective renal antioxidant mechanisms.

  18. Overexpressing the Sedum alfredii Cu/Zn Superoxide Dismutase Increased Resistance to Oxidative Stress in Transgenic Arabidopsis

    PubMed Central

    Li, Zhen; Han, Xiaojiao; Song, Xixi; Zhang, Yunxing; Jiang, Jing; Han, Qiang; Liu, Mingying; Qiao, Guirong; Zhuo, Renying

    2017-01-01

    Superoxide dismutase (SOD) is a very important reactive oxygen species (ROS)-scavenging enzyme. In this study, the functions of a Cu/Zn SOD gene (SaCu/Zn SOD), from Sedum alfredii, a cadmium (Cd)/zinc/lead co-hyperaccumulator of the Crassulaceae, was characterized. The expression of SaCu/Zn SOD was induced by Cd stress. Compared with wild-type (WT) plants, overexpression of SaCu/Zn SOD gene in transgenic Arabidopsis plants enhanced the antioxidative defense capacity, including SOD and peroxidase activities. Additionally, it reduced the damage associated with the overproduction of hydrogen peroxide (H2O2) and superoxide radicals (O2•-). The influence of Cd stress on ion flux across the root surface showed that overexpressing SaCu/Zn SOD in transgenic Arabidopsis plants has greater Cd uptake capacity existed in roots. A co-expression network based on microarray data showed possible oxidative regulation in Arabidopsis after Cd-induced oxidative stress, suggesting that SaCu/Zn SOD may participate in this network and enhance ROS-scavenging capability under Cd stress. Taken together, these results suggest that overexpressing SaCu/Zn SOD increased oxidative stress resistance in transgenic Arabidopsis and provide useful information for understanding the role of SaCu/Zn SOD in response to abiotic stress. PMID:28659953

  19. Oxidative stress response to acute hypobaric hypoxia and its association with indirect measurement of increased intracranial pressure: a field study

    PubMed Central

    Strapazzon, Giacomo; Malacrida, Sandro; Vezzoli, Alessandra; Dal Cappello, Tomas; Falla, Marika; Lochner, Piergiorgio; Moretti, Sarah; Procter, Emily; Brugger, Hermann; Mrakic-Sposta, Simona

    2016-01-01

    High altitude is the most intriguing natural laboratory to study human physiological response to hypoxic conditions. In this study, we investigated changes in reactive oxygen species (ROS) and oxidative stress biomarkers during exposure to hypobaric hypoxia in 16 lowlanders. Moreover, we looked at the potential relationship between ROS related cellular damage and optic nerve sheath diameter (ONSD) as an indirect measurement of intracranial pressure. Baseline measurement of clinical signs and symptoms, biological samples and ultrasonography were assessed at 262 m and after passive ascent to 3830 m (9, 24 and 72 h). After 24 h the imbalance between ROS production (+141%) and scavenging (−41%) reflected an increase in oxidative stress related damage of 50–85%. ONSD concurrently increased, but regression analysis did not infer a causal relationship between oxidative stress biomarkers and changes in ONSD. These results provide new insight regarding ROS homeostasis and potential pathophysiological mechanisms of acute exposure to hypobaric hypoxia, plus other disease states associated with oxidative-stress damage as a result of tissue hypoxia. PMID:27579527

  20. Long-Term Exposure to AZT, but not d4T, Increases Endothelial Cell Oxidative Stress and Mitochondrial Dysfunction

    PubMed Central

    Kline, Erik R.; Bassit, Leda; Hernandez-Santiago, Brenda I.; Detorio, Mervi A.; Liang, Bill; Kleinhenz, Dean J.; Walp, Erik R.; Dikalov, Sergey; Jones, Dean P.; Schinazi, Raymond F.

    2009-01-01

    Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (AZT) and stavudine (d4T), cause toxicities to numerous tissues, including the liver and vasculature. While much is known about hepatic NRTI toxicity, the mechanism of toxicity in endothelial cells is incompletely understood. Human aortic endothelial and HepG2 liver cells were exposed to 1 μM AZT or d4T for up to 5 weeks. Markers of oxidative stress, mitochondrial function, NRTI phosphorylation, mitochondrial DNA (mtDNA) levels, and cytotoxicity were monitored over time. In endothelial cells, AZT significantly oxidized glutathione redox potential, increased total cellular and mitochondrial-specific superoxide, decreased mitochondrial membrane potential, increased lactate release, and caused cell death from weeks 3 through 5. Toxicity occurred in the absence of di- and tri-phosphorylated AZT and mtDNA depletion. These data show that oxidative stress and mitochondrial dysfunction in endothelial cells occur with a physiologically relevant concentration of AZT, and require long-term exposure to develop. In contrast, d4T did not induce endothelial oxidative stress, mitochondrial dysfunction, or cytotoxicity despite the presence of d4T-triphosphate. Both drugs depleted mtDNA in HepG2 cells without causing cell death. Endothelial cells are more susceptible to AZT-induced toxicity than HepG2 cells, and AZT caused greater endothelial dysfunction than d4T because of its pro-oxidative effects. PMID:19067249

  1. Oxidative Stress Is Associated with an Increased Antioxidant Defense in Elderly Subjects: A Multilevel Approach

    PubMed Central

    Flores-Mateo, Gemma; Elosua, Roberto; Rodriguez-Blanco, Teresa; Basora-Gallisà, Josep; Bulló, Mònica; Salas-Salvadó, Jordi; Martínez-González, Miguel Ángel; Estruch, Ramon; Corella, Dolores; Fitó, Montserrat; Fiol, Miquel; Arós, Fernando; Gómez-Gracia, Enrique; Subirana, Isaac; Lapetra, José; Ruiz-Gutiérrez, Valentina; Sáez, Guillermo T.; Covas, Maria-Isabel

    2014-01-01

    Background Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. Methods We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selected from 8 primary health care centers (PHCCs). We assessed classical CVD risk factors, plasma oxidized low-density lipoproteins (ox-LDL), and glutathione peroxidase (GSH-Px) using multilevel statistical procedures. Results Mean GSH-Px value was 612 U/L (SE: 12 U/L), with variation between PHCCs ranging from 549 to 674 U/L (Variance = 1013.5; P<0.001). Between-participants variability within a PHCC accounted for 89% of the total variation. Both glucose and oxidized LDL were positively associated with GSH-Px activity after adjustment for possible confounder variables (P = 0.03 and P = 0.01, respectively). Conclusion In a population at high cardiovascular risk, a positive linear association was observed between plasma GSH-Px activity and both glucose and ox-LDL levels. The high GSH-Px activity observed when an oxidative stress situation occurred, such as hyperglycemia and lipid oxidative damage, could be interpreted as a healthy defensive response against oxidative injury in our cardiovascular risk population. PMID:25269026

  2. Oxidative stress is associated with an increased antioxidant defense in elderly subjects: a multilevel approach.

    PubMed

    Flores-Mateo, Gemma; Elosua, Roberto; Rodriguez-Blanco, Teresa; Basora-Gallisà, Josep; Bulló, Mònica; Salas-Salvadó, Jordi; Martínez-González, Miguel Ángel; Estruch, Ramon; Corella, Dolores; Fitó, Montserrat; Fiol, Miquel; Arós, Fernando; Gómez-Gracia, Enrique; Subirana, Isaac; Lapetra, José; Ruiz-Gutiérrez, Valentina; Sáez, Guillermo T; Covas, Maria-Isabel

    2014-01-01

    Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selected from 8 primary health care centers (PHCCs). We assessed classical CVD risk factors, plasma oxidized low-density lipoproteins (ox-LDL), and glutathione peroxidase (GSH-Px) using multilevel statistical procedures. Mean GSH-Px value was 612 U/L (SE: 12 U/L), with variation between PHCCs ranging from 549 to 674 U/L (Variance =  013.5; P<0.001). Between-participants variability within a PHCC accounted for 89% of the total variation. Both glucose and oxidized LDL were positively associated with GSH-Px activity after adjustment for possible confounder variables (P = 0.03 and P = 0.01, respectively). In a population at high cardiovascular risk, a positive linear association was observed between plasma GSH-Px activity and both glucose and ox-LDL levels. The high GSH-Px activity observed when an oxidative stress situation occurred, such as hyperglycemia and lipid oxidative damage, could be interpreted as a healthy defensive response against oxidative injury in our cardiovascular risk population.

  3. Increased levels of oxidative stress markers in the peritoneal fluid of women with endometriosis.

    PubMed

    Polak, Grzegorz; Wertel, Iwona; Barczyński, Bartłomiej; Kwaśniewski, Wojciech; Bednarek, Wiesława; Kotarski, Jan

    2013-06-01

    To evaluate 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane levels in the peritoneal fluid (PF) of women with endometriosis. One hundred and ten women with laparoscopically and histopathologically confirmed endometriosis and, as reference groups, 119 patients with simple serous (n=78) and dermoid (n=41) ovarian cysts were studied. Peritoneal fluid 8-OHdG and 8-isoprostane concentrations were evaluated by enzyme-linked immunosorbent assays. 8-OHdG and 8-isoprostane levels in peritoneal fluid were significantly higher in patients with endometriosis compared with the reference groups. Higher PF 8-OHdG and 8-isoprostane concentrations were observed in patients with advanced stages of endometriosis. A statistically significant positive correlation was found between 8-OHdG and 8-isoprostane levels in peritoneal fluid. Endometriosis induces greater oxidative stress and frequent DNA mutations in peritoneal fluid than nonendometriotic ovarian cysts. The most severe oxidative stress occurs in the peritoneal cavity of women with more advanced stages of the disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Functional cobalamin (vitamin B12) deficiency: role of advanced age and disorders associated with increased oxidative stress.

    PubMed

    Solomon, L R

    2015-06-01

    Functional cobalamin (Cbl; vitamin B12) deficiency (that is, high levels of the Cbl-dependent metabolites, methylmalonic acid (MMA) and homocysteine (HCys), despite normal serum Cbl values) is common in the elderly and is associated with neurocognitive abnormalities, but its cause is unknown. As only reduced Cbls are metabolically active, the possibility that functional Cbl deficiency is associated with disorders having biomarkers indicative of increased oxidative stress (oxidant risks) was considered. A retrospective record review of community-dwelling adults evaluated over a 12-year period for Cbl deficiency in a primary care setting who had serum Cbl values ⩾400 pg/ml (n=170). When no oxidant risks were present, older subjects (⩾70 years) had higher metabolite values than younger individuals (<70 years). MMA values were even higher in the elderly when one oxidant risk was present and in younger subjects when two or more oxidant risks were present. Even at Cbl levels ⩾800 pg/ml, MMA values were increased in 73% of elderly subjects with at least one oxidant risk. HCys values were also higher in both age groups when at least two oxidant risks were present. Cyanocobalamin therapy decreased MMA and HCys values in 86 and 76% of subjects, respectively, with nonresponders more likely to have two or more oxidant risks. Functional Cbl deficiency is associated with disorders marked by increased oxidative stress particularly in the elderly; it occurs even when Cbl levels are high and is not consistently corrected with high-dose cyanocobalamin therapy. Thus, current approaches to recognizing and managing this disorder may be inadequate.

  5. Metabolic syndrome increases oxidative stress but does not influence disability and short-time outcome in acute ischemic stroke patients.

    PubMed

    Simão, Andrea Name Colado; Lehmann, Marcio Francisco; Alfieri, Daniela Frizon; Meloni, Milena Zardetto; Flauzino, Tamires; Scavuzzi, Bruna Miglioranza; de Oliveira, Sayonara Rangel; Lozovoy, Marcell Alysson Batisti; Dichi, Isaias; Reiche, Edna Maria Vissoci

    2015-12-01

    Oxidative stress has been implicated in the pathophysiology of cardiovascular disease and MetS and it may be one of molecular mechanisms involved in stroke. The aims of the present study were to verify differences in oxidative stress markers in acute ischemic stroke patients with and without MetS and to verify whether MetS influences disability and short time outcome of the patients. 148 patients with acute ischemic stroke were divided in two groups: with MetS (n = 92) and without MetS (n = 56). The modified Rankin Scale (mRS) was used for measuring the functional disability after 3-month follow-up. The study assessed the metabolic profile and oxidative stress markers. Stroke patients with MetS had higher levels of lipid hydroperoxides (p < 0.0001) and advanced oxidation protein products (AOPP, p = 0.0302) than those without MetS. Hydroperoxides were directly and independently associated with MetS (OR: 1.000, 95 % IC = 1.000-1.000, p = 0.005). Linear regression demonstrated that AOPP levels (R(2) = 0.281, p < 0.0001) and oxidative stress index (OSI, R(2) = 0.223, p < 0.0001) were directly associated with triglycerides levels and hydroperoxides levels was also directly associated with glucose levels (R(2) = 0.080, p = 0.013. The mRS and short-come outcome did not differ after 3 months in both groups. In conclusion, an increase in oxidative stress markers was shown in acute ischemic stroke patients with MetS and this elevation seems to be involved mainly with changes in lipid profile, but the presence of MetS did not influence short-time disability and survival of the acute ischemic stroke patients.

  6. Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

    PubMed Central

    Wolff, Valérie; Schlagowski, Anna-Isabel; Rouyer, Olivier; Charles, Anne-Laure; Singh, François; Auger, Cyril; Schini-Kerth, Valérie; Marescaux, Christian; Raul, Jean-Sébastien; Zoll, Joffrey; Geny, Bernard

    2015-01-01

    Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities), Vsucc (complexes II, III, and IV activities), Vtmpd (complex IV activity), together with mitochondrial coupling (Vmax/V0), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2) production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P < 0.0001), Vsucc (−65%; P < 0.0001), and Vtmpd (−3.5%; P < 0.001). Mitochondrial coupling (Vmax/V0) was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P < 0.001). Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P < 0.05) and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P < 0.001). Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient's vulnerability to stroke. PMID:25654095

  7. Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans

    PubMed Central

    Micallef, Michelle; Lexis, Louise; Lewandowski, Paul

    2007-01-01

    Background Red wine contains a naturally rich source of antioxidants, which may protect the body from oxidative stress, a determinant of age-related disease. The current study set out to determine the in vivo effects of moderate red wine consumption on antioxidant status and oxidative stress in the circulation. Methods 20 young (18–30 yrs) and 20 older (≥ 50 yrs) volunteers were recruited. Each age group was randomly divided into treatment subjects who consumed 400 mL/day of red wine for two weeks, or control subjects who abstained from alcohol for two weeks, after which they crossed over into the other group. Blood samples were collected before and after red wine consumption and were used for analysis of whole blood glutathione (GSH), plasma malondialdehyde (MDA) and serum total antioxidant status. Results Results from this study show consumption of red wine induced significant increases in plasma total antioxidant status (P < 0.03), and significant decreases in plasma MDA (P < 0.001) and GSH (P < 0.004) in young and old subjects. The results show that the consumption of 400 mL/day of red wine for two weeks, significantly increases antioxidant status and decreases oxidative stress in the circulation Conclusion It may be implied from this data that red wine provides general oxidative protection and to lipid systems in circulation via the increase in antioxidant status. PMID:17888186

  8. Tetrahydrocannabinol induces brain mitochondrial respiratory chain dysfunction and increases oxidative stress: a potential mechanism involved in cannabis-related stroke.

    PubMed

    Wolff, Valérie; Schlagowski, Anna-Isabel; Rouyer, Olivier; Charles, Anne-Laure; Singh, François; Auger, Cyril; Schini-Kerth, Valérie; Marescaux, Christian; Raul, Jean-Sébastien; Zoll, Joffrey; Geny, Bernard

    2015-01-01

    Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities V max (complexes I, III, and IV activities), V succ (complexes II, III, and IV activities), V tmpd (complex IV activity), together with mitochondrial coupling (V max/V 0), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2) production, measured with Amplex Red. THC significantly decreased V max (-71%; P < 0.0001), V succ (-65%; P < 0.0001), and V tmpd (-3.5%; P < 0.001). Mitochondrial coupling (V max/V 0) was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P < 0.001). Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P < 0.05) and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P < 0.001). Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient's vulnerability to stroke.

  9. Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure

    PubMed Central

    Lim, Jinhwan; Nakamura, Brooke N.; Mohar, Isaac; Kavanagh, Terrance J.

    2015-01-01

    Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm−/− mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm−/− vs Gclm+/+ ovaries. Prepubertal Gclm−/− and Gclm+/+ mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm−/− mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm−/− ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm−/− vs Gclm+/+ ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm−/− mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development. PMID:26083875

  10. Increased susceptibility to fundus camera-delivered light-induced retinal degeneration in mice deficient in oxidative stress response proteins.

    PubMed

    Ding, Yi; Aredo, Bogale; Zhong, Xin; Zhao, Cynthia X; Ufret-Vincenty, Rafael L

    2017-06-01

    Oxidative stress is an important contributor to the pathogenesis of many retinal diseases including age-related macular degeneration and retinal dystrophies. Light-induced retinal degeneration (LIRD) can serve as a model in which to study the response of the retina to stress. Of note, many genetic mutant mice are in a C57BL/6 J background and are thus resistant to the usual LIRD models. We recently developed a new model of fundus camera-delivered light-induced retinal degeneration (FCD-LIRD) which is effective in strains of mice expressing the light-resistant variant of RPE65 (450Met), including C57BL/6 J. In this work we investigated whether FCD-LIRD would be useful as a model in which to test the effect of genetic mutations on the response of the retina to stress. Furthermore, we tested whether oxidative stress plays an important role in the setting of this new FCD-LIRD model. FCD-LIRD was applied to C57BL/6 J mice and to mice simultaneously deficient in three proteins that are important in the response of the retina to oxidative stress (SOD1, DJ-1 and Parkin). Using fundus photography, we found that retinal damage was dramatically increased in the SOD1/DJ-1/Parkin deficient mice compared to C57BL/6 J. Outer retinal OCT volume and RPE cell morphology analysis in ZO-1-stained flat mounts added support to these findings. Gene expression analysis confirmed a strong oxidative stress response after FCD-LIRD, which was differentially altered in the SOD1/DJ1/Parkin deficient mice. We conclude that FCD-LIRD is useful to study the effect of genetic mutations on the response of the retina to light stress in light-resistant strains of mice. Furthermore, oxidative stress seems to be an important component of FCD-LIRD. Finally, we have established protocols to quantify the effect of FCD-LIRD on the retina and RPE which will be useful for future studies. Further dissection of the mechanisms by which the retina responds to light-induced oxidative stress may result in new

  11. Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

    PubMed

    Ugusman, Azizah; Zakaria, Zaiton; Hui, Chua Kien; Nordin, Nor Anita Megat Mohd

    2010-07-01

    Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

  12. Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

    PubMed Central

    Maes, Michael; Kubera, Marta; Uytterhoeven, Marc; Vrydags, Nicolas; Bosmans, Eugene

    2011-01-01

    Summary Background There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress. Material/Methods Blood was collected from 56 patients with ME/CFS and 37 normal volunteers. Severity of ME/CFS was measured using the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Results Plasma peroxide concentrations were significantly higher in patients with ME/CFS than in normal controls. There was a trend towards significantly higher serum oxLDL antibodies in ME/CFS than in controls. Both biomarkers contributed significantly in discriminating between patients with ME/CFS and normal controls. Plasma peroxide and serum oxLDL antibody levels were both significantly related to one of the FF symptoms. Conclusions The results show that ME/CFS is characterized by increased oxidative stress. PMID:21455120

  13. Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

    PubMed

    Maes, Michael; Kubera, Marta; Uytterhoeven, Marc; Vrydags, Nicolas; Bosmans, Eugene

    2011-04-01

    There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress. Blood was collected from 56 patients with ME/CFS and 37 normal volunteers. Severity of ME/CFS was measured using the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Plasma peroxide concentrations were significantly higher in patients with ME/CFS than in normal controls. There was a trend towards significantly higher serum oxLDL antibodies in ME/CFS than in controls. Both biomarkers contributed significantly in discriminating between patients with ME/CFS and normal controls. Plasma peroxide and serum oxLDL antibody levels were both significantly related to one of the FF symptoms. The results show that ME/CFS is characterized by increased oxidative stress.

  14. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    SciTech Connect

    Yang, Yuehua Zheng, Xinfeng Li, Bo Jiang, Shengdan Jiang, Leisheng

    2014-08-15

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.

  15. Croton argenteus preparation inhibits initial growth, mitochondrial respiration and increase the oxidative stress from Senna occidentalis seedlings.

    PubMed

    Rech, Katlin S; Silva, Cristiane B; Kulik, Juliana D; Dias, Josiane F G; Zanin, Sandra M W; Kerber, Vitor A; Ocampos, Fernanda M M; Dalarmi, Luciane; Santos, Gedir O; Simionatto, Euclésio; Lima, Cristina P; Miguel, Obdúlio G; Miguel, Marilis D

    2015-01-01

    Senna ocidentalis is a weed, native to Brazil, considered to infest crops and plantations, and is responsible for yield losses of several crops, particularly soybean. The aim of this work was to evaluate if the Croton argenteus extract and fractions possess phytotoxic activity on S. ocidentalis. The crude ethanolic extract (CEE) and its hexanic (HF), chloroformic (CLF) and ethyl acetate (EAF) fractions were tested in germination, growth, oxidative stress increase, Adenosine triphosphate, L-malate and succinate synthesis. The crude extract and its fractions slowed down the germination of S. ocidentalis and decreased the final percentage of germination. Oxidative stress was also increased in the seedlings, by an increase of catalase, peroxidase, superoxide dismutase, glutathione reductase and lipid peroxidation; and it became clear that the ethyl acetate fraction was more phytotoxic. The results indicate that the crude extract and fractions of C. argenteus compromise the mitochondrial energy metabolism, by the inhibition of mitochondrial ATP production, with a decrease in the production of L-malate and succinate. The ethyl acetate fraction of C. argenteus showed high activity on germination and growth, and these effects take place by means of mitochondrial metabolism alterations and increase the oxidative stress, leading the seedling death.

  16. 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.

  17. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress

    PubMed Central

    Morita, Norishige; Sovari, Ali A.; Xie, Yuanfang; Fishbein, Michael C.; Mandel, William J.; Garfinkel, Alan; Lin, Shien-Fong; Chen, Peng-Sheng; Xie, Lai-Hua; Chen, Fuhua; Qu, Zhilin; Weiss, James N.

    2009-01-01

    Oxidative stress with hydrogen peroxide (H2O2) readily promotes early afterdepolarizations (EADs) and triggered activity (TA) in isolated rat and rabbit ventricular myocytes. Here we examined the effects of H2O2 on arrhythmias in intact Langendorff rat and rabbit hearts using dual-membrane voltage and intracellular calcium optical mapping and glass microelectrode recordings. Young adult rat (3–5 mo, N = 25) and rabbit (3–5 mo, N = 6) hearts exhibited no arrhythmias when perfused with H2O2 (0.1–2 mM) for up to 3 h. However, in 33 out of 35 (94%) aged (24–26 mo) rat hearts, 0.1 mM H2O2 caused EAD-mediated TA, leading to ventricular tachycardia (VT) and fibrillation (VF). Aged rabbits (life span, 8–12 yr) were not available, but 4 of 10 middle-aged rabbits (3–5 yr) developed EADs, TA, VT, and VF. These arrhythmias were suppressed by the reducing agent N-acetylcysteine (2 mM) and CaMKII inhibitor KN-93 (1 μM) but not by its inactive form (KN-92, 1 μM). There were no significant differences between action potential duration (APD) or APD restitution slope before or after H2O2 in aged or young adult rat hearts. In histological sections, however, trichrome staining revealed that aged rat hearts exhibited extensive fibrosis, ranging from 10–90%; middle-aged rabbit hearts had less fibrosis (5–35%), whereas young adult rat and rabbit hearts had <4% fibrosis. In aged rat hearts, EADs and TA arose most frequently (70%) from the left ventricular base where fibrosis was intermediate (∼30%). Computer simulations in two-dimensional tissue incorporating variable degrees of fibrosis showed that intermediate (but not mild or severe) fibrosis promoted EADs and TA. We conclude that in aged ventricles exposed to oxidative stress, fibrosis facilitates the ability of cellular EADs to emerge and generate TA, VT, and VF at the tissue level. PMID:19767530

  18. α-Lipoic acid reduces neurogenic hypertension by blunting oxidative stress-mediated increase in ADAM17.

    PubMed

    de Queiroz, Thyago M; Xia, Huijing; Filipeanu, Catalin M; Braga, Valdir A; Lazartigues, Eric

    2015-09-01

    We previously reported that type 2 angiotensin-converting enzyme (ACE2) compensatory activity is impaired by the disintegrin and metalloprotease 17 (ADAM17), and lack of ACE2 is associated with oxidative stress in neurogenic hypertension. To investigate the relationship between ADAM17 and oxidative stress, Neuro2A cells were treated with ANG II (100 nM) 24 h after vehicle or α-lipoic acid (LA, 500 μM). ADAM17 expression was increased by ANG II (120.5 ± 9.1 vs. 100.2 ± 0.8%, P < 0.05) and decreased after LA (69.0 ± 0.3 vs. 120.5 ± 9.1%, P < 0.05). In another set of experiments, LA reduced ADAM17 (92.9 ± 5.3 vs. 100.0 ± 11.2%, P < 0.05) following its overexpression. Moreover, ADAM17 activity was reduced by LA in ADAM17-overexpressing cells [109.5 ± 19.8 vs. 158.0 ± 20.0 fluorescence units (FU)·min(-1)·μg protein(-1), P < 0.05], in which ADAM17 overexpression increased oxidative stress (114.1 ± 2.5 vs. 101.0 ± 1.0%, P < 0.05). Conversely, LA-treated cells attenuated ADAM17 overexpression-induced oxidative stress (76.0 ± 9.1 vs. 114.1 ± 2.5%, P < 0.05). In deoxycorticosterone acetate (DOCA)-salt hypertensive mice, a model in which ADAM17 expression and activity are increased, hypertension was blunted by pretreatment with LA (119.0 ± 2.4 vs. 131.4 ± 2.2 mmHg, P < 0.05). In addition, LA improved dysautonomia and baroreflex sensitivity. Furthermore, LA blunted the increase in NADPH oxidase subunit expression, as well as the increase in ADAM17 and decrease in ACE2 activity in the hypothalamus of DOCA-salt hypertensive mice. Taken together, these data suggest that LA might preserve ACE2 compensatory activity by breaking the feedforward cycle between ADAM17 and oxidative stress, resulting in a reduction of neurogenic hypertension. Copyright © 2015 the American Physiological Society.

  19. α-Lipoic acid reduces neurogenic hypertension by blunting oxidative stress-mediated increase in ADAM17

    PubMed Central

    de Queiroz, Thyago M.; Xia, Huijing; Filipeanu, Catalin M.; Braga, Valdir A.

    2015-01-01

    We previously reported that type 2 angiotensin-converting enzyme (ACE2) compensatory activity is impaired by the disintegrin and metalloprotease 17 (ADAM17), and lack of ACE2 is associated with oxidative stress in neurogenic hypertension. To investigate the relationship between ADAM17 and oxidative stress, Neuro2A cells were treated with ANG II (100 nM) 24 h after vehicle or α-lipoic acid (LA, 500 μM). ADAM17 expression was increased by ANG II (120.5 ± 9.1 vs. 100.2 ± 0.8%, P < 0.05) and decreased after LA (69.0 ± 0.3 vs. 120.5 ± 9.1%, P < 0.05). In another set of experiments, LA reduced ADAM17 (92.9 ± 5.3 vs. 100.0 ± 11.2%, P < 0.05) following its overexpression. Moreover, ADAM17 activity was reduced by LA in ADAM17-overexpressing cells [109.5 ± 19.8 vs. 158.0 ± 20.0 fluorescence units (FU)·min−1·μg protein−1, P < 0.05], in which ADAM17 overexpression increased oxidative stress (114.1 ± 2.5 vs. 101.0 ± 1.0%, P < 0.05). Conversely, LA-treated cells attenuated ADAM17 overexpression-induced oxidative stress (76.0 ± 9.1 vs. 114.1 ± 2.5%, P < 0.05). In deoxycorticosterone acetate (DOCA)-salt hypertensive mice, a model in which ADAM17 expression and activity are increased, hypertension was blunted by pretreatment with LA (119.0 ± 2.4 vs. 131.4 ± 2.2 mmHg, P < 0.05). In addition, LA improved dysautonomia and baroreflex sensitivity. Furthermore, LA blunted the increase in NADPH oxidase subunit expression, as well as the increase in ADAM17 and decrease in ACE2 activity in the hypothalamus of DOCA-salt hypertensive mice. Taken together, these data suggest that LA might preserve ACE2 compensatory activity by breaking the feedforward cycle between ADAM17 and oxidative stress, resulting in a reduction of neurogenic hypertension. PMID:26254330

  20. Increased ANG II sensitivity following recovery from acute kidney injury: role of oxidant stress in skeletal muscle resistance arteries

    PubMed Central

    Phillips, Shane A.; Pechman, Kimberly R.; Leonard, Ellen C.; Friedrich, Jessica L.; Bian, Jing-Tan; Beal, Alisa G.

    2010-01-01

    Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) results in prolonged impairment of peripheral (i.e., nonrenal) vascular function since skeletal muscle resistance arteries derived from rats 5 wk post-I/R injury, show enhanced responses to ANG II stimulation but not other constrictors. Because vascular superoxide increases ANG II sensitivity, we hypothesized that peripheral responsiveness following recovery from AKI was attributable to vascular oxidant stress. Gracilis arteries (GA) isolated from post-I/R rats (∼5 wk recovery) showed significantly greater superoxide levels relative to sham-operated controls, as detected by dihydroeithidium, which was further augmented by acute ANG II stimulation in vitro. Hydrogen peroxide measured by dichlorofluorescein was not affected by ANG II. GA derived from postischemic animals manifested significantly greater constrictor responses in vitro to ANG II than GA from sham-operated controls. The addition of the superoxide scavenging reagent Tempol (10−5 M) normalized the response to values similar to sham-operated controls. Apocynin (10−6 M) and endothelial denudation nearly abrogated all ANG II-stimulated constrictor activity in GA from post-AKI rats, suggesting an important role for an endothelial-derived source of peripheral oxidative stress. Apocynin treatment in vivo abrogated GA oxidant stress and attenuated ANG II-induced pressor responses post-AKI. Interestingly, gene expression studies in GA vessels indicated a paradoxical reduction in NADPH oxidase subunit and AT1-receptor genes and no effect on several antioxidant genes. Taken together, this study demonstrates that AKI alters peripheral vascular responses by increasing oxidant stress, likely in the endothelium, via an undefined mechanism. PMID:20335375

  1. Increased ANG II sensitivity following recovery from acute kidney injury: role of oxidant stress in skeletal muscle resistance arteries.

    PubMed

    Phillips, Shane A; Pechman, Kimberly R; Leonard, Ellen C; Friedrich, Jessica L; Bian, Jing-Tan; Beal, Alisa G; Basile, David P

    2010-06-01

    Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) results in prolonged impairment of peripheral (i.e., nonrenal) vascular function since skeletal muscle resistance arteries derived from rats 5 wk post-I/R injury, show enhanced responses to ANG II stimulation but not other constrictors. Because vascular superoxide increases ANG II sensitivity, we hypothesized that peripheral responsiveness following recovery from AKI was attributable to vascular oxidant stress. Gracilis arteries (GA) isolated from post-I/R rats (approximately 5 wk recovery) showed significantly greater superoxide levels relative to sham-operated controls, as detected by dihydroeithidium, which was further augmented by acute ANG II stimulation in vitro. Hydrogen peroxide measured by dichlorofluorescein was not affected by ANG II. GA derived from postischemic animals manifested significantly greater constrictor responses in vitro to ANG II than GA from sham-operated controls. The addition of the superoxide scavenging reagent Tempol (10(-5) M) normalized the response to values similar to sham-operated controls. Apocynin (10(-6) M) and endothelial denudation nearly abrogated all ANG II-stimulated constrictor activity in GA from post-AKI rats, suggesting an important role for an endothelial-derived source of peripheral oxidative stress. Apocynin treatment in vivo abrogated GA oxidant stress and attenuated ANG II-induced pressor responses post-AKI. Interestingly, gene expression studies in GA vessels indicated a paradoxical reduction in NADPH oxidase subunit and AT(1)-receptor genes and no effect on several antioxidant genes. Taken together, this study demonstrates that AKI alters peripheral vascular responses by increasing oxidant stress, likely in the endothelium, via an undefined mechanism.

  2. Overexpression of Heat Shock Factor Gene HsfA3 Increases Galactinol Levels and Oxidative Stress Tolerance in Arabidopsis

    PubMed Central

    Song, Chieun; Chung, Woo Sik; Lim, Chae Oh

    2016-01-01

    Heat shock factors (Hsfs) are central regulators of abiotic stress responses, especially heat stress responses, in plants. In the current study, we characterized the activity of the Hsf gene HsfA3 in Arabidopsis under oxidative stress conditions. HsfA3 transcription in seedlings was induced by reactive oxygen species (ROS), exogenous hydrogen peroxide (H2O2), and an endogenous H2O2 propagator, 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB). HsfA3-overexpressing transgenic plants exhibited increased oxidative stress tolerance compared to untransformed wild-type plants (WT), as revealed by changes in fresh weight, chlorophyll fluorescence, and ion leakage under light conditions. The expression of several genes encoding galactinol synthase (GolS), a key enzyme in the biosynthesis of raffinose family oligosaccharides (RFOs), which function as antioxidants in plant cells, was induced in HsfA3 overexpressors. In addition, galactinol levels were higher in HsfA3 overexpressors than in WT under unstressed conditions. In transient transactivation assays using Arabidopsis leaf protoplasts, HsfA3 activated the transcription of a reporter gene driven by the GolS1 or GolS2 promoter. Electrophoretic mobility shift assays showed that GolS1 and GolS2 are directly regulated by HsfA3. Taken together, these findings provide evidence that GolS1 and GolS2 are directly regulated by HsfA3 and that GolS enzymes play an important role in improving oxidative stress tolerance by increasing galactinol biosynthesis in Arabidopsis. PMID:27109422

  3. Oxidative stress is increased in critically ill patients according to antioxidant vitamins intake, independent of severity: a cohort study

    PubMed Central

    Abilés, Jimena; de la Cruz, Antonio Pérez; Castaño, José; Rodríguez-Elvira, Manuel; Aguayo, Eduardo; Moreno-Torres, Rosario; Llopis, Juan; Aranda, Pilar; Argüelles, Sandro; Ayala, Antonio; de la Quintana, Alberto Machado; Planells, Elena Maria

    2006-01-01

    Introduction Critically ill patients suffer from oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Although ROS/RNS are constantly produced under normal circumstances, critical illness can drastically increase their production. These patients have reduced plasma and intracellular levels of antioxidants and free electron scavengers or cofactors, and decreased activity of the enzymatic system involved in ROS detoxification. The pro-oxidant/antioxidant balance is of functional relevance during critical illness because it is involved in the pathogenesis of multiple organ failure. In this study the objective was to evaluate the relation between oxidative stress in critically ill patients and antioxidant vitamin intake and severity of illness. Methods Spectrophotometry was used to measure in plasma the total antioxidant capacity and levels of lipid peroxide, carbonyl group, total protein, bilirubin and uric acid at two time points: at intensive care unit (ICU) admission and on day seven. Daily diet records were kept and compliance with recommended dietary allowance (RDA) of antioxidant vitamins (A, C and E) was assessed. Results Between admission and day seven in the ICU, significant increases in lipid peroxide and carbonyl group were associated with decreased antioxidant capacity and greater deterioration in Sequential Organ Failure Assessment score. There was significantly greater worsening in oxidative stress parameters in patients who received antioxidant vitamins at below 66% of RDA than in those who received antioxidant vitamins at above 66% of RDA. An antioxidant vitamin intake from 66% to 100% of RDA reduced the risk for worsening oxidative stress by 94% (ods ratio 0.06, 95% confidence interval 0.010 to 0.39), regardless of change in severity of illness (Sequential Organ Failure Assessment score). Conclusion The critical condition of patients admitted to the ICU is associated with worsening oxidative stress. Intake of

  4. Oxidative stress and anxiety

    PubMed Central

    Rammal, Hassan; Soulimani, Rachid

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal anxiety and also on a possible causal relationship between cellular oxidative stress and emotional stress. This review examines the recent discoveries made on the link between oxidative status and normal anxiety levels and the putative role of oxidative stress in genesis of anxiety. We discuss the different opinions and questions that exist in the field and review the methodological approaches that are being used to determine a causal relationship between oxidative and emotional stress. PMID:20357926

  5. High Dietary Iron and Radiation Exposure Increase Biomarkers of Oxidative Stress in Blood and Liver of Rats

    NASA Technical Reports Server (NTRS)

    Morgan, Jennifer L. L.; Theriot, Corey A.; Wu, Honglu; Smith, Scott M.; Zwart, Sara R.

    2012-01-01

    Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs-137 every other day for 16 days for a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet compared to 45 mg Fe/kg for controls) in Sprague-Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation treatment increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. We thus found preliminary indications of synergistic effects of radiation exposure and increased dietary Fe, warranting further study. This study was funded by the NASA Human Research Project.

  6. Increase nitric oxide and oxidative stress in dogs experimentally infected by Ehrlichia canis: effect on the pathogenesis of the disease.

    PubMed

    Da Silva, Aleksandro S; Munhoz, Thiago D; Faria, Joice L M; Vargas-Hérnandez, Giovanni; Machado, Rosangela Z; Almeida, Taís C; Moresco, Rafael N; Stefani, Lenita M; Tinucci-Costa, Mirela

    2013-06-28

    The aim of this study was to evaluate nitric oxide levels, lipid peroxidation, protein oxidation and glutathione reductase activity in serum of dogs experimentally infected by Ehrlichia canis. Banked serum samples of dogs divided into two groups were used: negative control (n=5) and infected by E. canis (n=5). The concentration of nitrite/nitrate (NOx), lipid peroxidation (TBARS), advanced oxidation protein products (AOPP), and glutathione reductase (GR) activity in sera were evaluated. Samples were collected on days 0, 3, 6, 18 and 30 post-infection (PI). NOx and TBARS levels were significantly (P<0.05) higher in the infected group at 18 and 30 days PI, as well as AOPP levels at 30 days PI when compared to samples from control group. The GR activity was significant (P<0.05) increased in serum of dogs infected by E. canis on days 18 and 30 PI. Based on the increased levels of NOx, TBARS, AOPP and GR activity we concluded that dogs experimentally infected by E. canis develop a state of redox imbalance and that these changes might be involved in the pathophysiology of the disease.

  7. Oxidative stress, nitric oxide, and diabetes.

    PubMed

    Pitocco, Dario; Zaccardi, Francesco; Di Stasio, Enrico; Romitelli, Federica; Santini, Stefano A; Zuppi, Cecilia; Ghirlanda, Giovanni

    2010-01-01

    In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the "final common pathway", through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients.

  8. Oxidative Stress, Nitric Oxide, and Diabetes

    PubMed Central

    Pitocco, Dario; Zaccardi, Francesco; Di Stasio, Enrico; Romitelli, Federica; Santini, Stefano A.; Zuppi, Cecilia; Ghirlanda, Giovanni

    2010-01-01

    In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the “final common pathway”, through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients. PMID:20703435

  9. Systemic oxidative stress is increased to a greater degree in young, obese women following consumption of a high fat meal

    PubMed Central

    Fisher-Wellman, Kelsey H

    2009-01-01

    High fat meals induce oxidative stress, which is associated with the pathogenesis of disease. Obese individuals have elevated resting biomarkers of oxidative stress compared to non-obese. We compared blood oxidative stress biomarkers in obese (n = 14; 30 ± 2 years; BMI 35 ± 1 kg•m−2) and non-obese (n = 16; 24 ± 2 years; BMI 23 ± 1 kg•m−2) women, in response to a high fat meal. Blood samples were collected pre-meal (fasted), and at 1, 2, 4 and 6 hours post meal, and assayed for trolox equivalent antioxidant capacity (TEAC), xanthine oxidase activity (XO), hydrogen peroxide (H2O2), malondialdehyde (MDA), triglycerides (TAG), and glucose. An obesity status effect was noted for all variables (p < 0.001; MDA p = 0.05), with obese women having higher values than non-obese, except for TEAC, for which values were lower. Time main effects were noted for all variables (p ≤ 0.01) except for TEAC and glucose, with XO, H2O2, MDA and TAG increasing following feeding with a peak response at the four or six hour post feeding time point. While values tended to decline by six hours post feeding in the non-obese women (agreeing with previous studies), they were maintained (MDA) or continued to increase (XO, H2O2 and TAG) in the obese women. While no interaction effects were noted (p > 0.05), contrasts revealed greater values in obese compared to non-obese women for XO, H2O2, MDA, TAG and glucose, and lower values for TEAC at times from 1–6 hours post feeding (p ≤ 0.03). We conclude that young, obese women experience a similar pattern of increase in blood oxidative stress biomarkers in response to a high fat meal, as compared to non-obese women. However, the overall oxidative stress is greater in obese women, and values appear to remain elevated for longer periods of time post feeding. These data provide insight into another potential mechanism related to obesity-mediated morbidity. PMID:20046641

  10. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

    PubMed Central

    Canelles, Sandra; Argente, Jesús; Barrios, Vicente

    2016-01-01

    ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  11. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model.

    PubMed

    Baquedano, Eva; Burgos-Ramos, Emma; Canelles, Sandra; González-Rodríguez, Agueda; Chowen, Julie A; Argente, Jesús; Barrios, Vicente; Valverde, Angela M; Frago, Laura M

    2016-05-01

    Insulin receptor substrate-2-deficient (IRS2(-/-)) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2(-/-) mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2(-/-) mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2(-/-) mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2(-/-) mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. © 2016. Published by The Company of Biologists Ltd.

  12. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss.

    PubMed

    Yang, Yuehua; Zheng, Xinfeng; Li, Bo; Jiang, Shengdan; Jiang, Leisheng

    2014-08-15

    The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. 36 female Sprague-Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  13. Oxidative stress and myocarditis.

    PubMed

    Tada, Yuko; Suzuki, Jun-Ichi

    2016-01-01

    Reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide are produced highly in myocarditis. ROS, which not only act as effectors for pathogen killing but also mediate signal transduction in the stress responsive pathways, are closely related with both innate and adaptive immunity. On the other hand, oxidative stress overwhelming the capacity of anti-oxidative system generated in severe inflammation has been suggested to damage tissues and exacerbate inflammation. Oxidative stress worsens the autoimmunological process of myocarditis, and suppression of the anti-oxidative system and long-lasting oxidative stress could be one of the pathological mechanisms of cardiac remodeling leading to inflammatory cardiomyopathy. Oxidative stress is considered to be one of the promising treatment targets of myocarditis. Evidences of anti-oxidative treatments in myocarditis have not been fully established. Basic strategies of anti-oxidative treatments include inhibition of ROS production, activation of anti-oxidative enzymes and elimination of generated free radicals. ROS are produced by mitochondrial respiratory chain reactions and enzymes including NADPH oxidases, cyclooxygenase, and xanthine oxidase. Other systems involved in inflammation and stress response, such as NF-κB, Nrf2/Keap1, and neurohumoral factors also influence oxidative stress in myocarditis. The efficacy of anti-oxidative treatments could also depend on the etiology and the phases of myocarditis. We review in this article the pathological significance of ROS and oxidative stress, and the potential anti-oxidative treatments in myocarditis.

  14. N-acetylcysteine reverses existing cognitive impairment and increased oxidative stress in glutamate transporter type 3 deficient mice.

    PubMed

    Cao, L; Li, L; Zuo, Z

    2012-09-18

    Oxidative stress contributes significantly to brain aging. Animals lacking glutamate transporter type 3 (EAAT3) have a decreased level of glutathione, the major intracellular anti-oxidant, in neurons, and present with early onset of brain aging including brain atrophy and cognitive impairment at 11 months of age. Here, 12-month-old male EAAT3 knockout mice received intraperitoneal injection of N-acetylcysteine (NAC) at 150 mg/kg once every day for 4 weeks. NAC is a membrane permeable cysteine precursor that can work as a substrate for glutathione synthesis. EAAT3 knockout mice that received saline injection or did not receive any injection were also included in the study. EAAT3 knockout mice had significantly less freezing behavior than age- and gender-matched wild-type mice in context- and tone-related fear conditioning tests. The knockout mice also had decreased levels of glutathione and increased levels of 4-hydroxy-2-nonenal and proteins containing nitrotyrosine, indicators of oxidative stress, in the cerebral cortex and hippocampus. NAC but not saline injection attenuated these behavioral and biochemical changes in the EAAT3 knockout mice. These results suggest that improvement of anti-oxidative capacity in neurons reverses the existing cognitive impairment in aging brains, implying a potential role of glutathione replacement in cognitive improvement of aging population.

  15. Saikosaponin-D attenuates heat stress-induced oxidative damage in LLC-PK1 cells by increasing the expression of anti-oxidant enzymes and HSP72.

    PubMed

    Zhang, Bao-Zhen; Guo, Xiao-Tong; Chen, Jian-Wei; Zhao, Yuan; Cong, Xia; Jiang, Zhong-Ling; Cao, Rong-Feng; Cui, Kai; Gao, Shan-Song; Tian, Wen-Ru

    2014-01-01

    Heat stress stimulates the production of reactive oxygen species (ROS), which cause oxidative damage in the kidney. This study clarifies the mechanism by which saikosaponin-d (SSd), which is extracted from the roots of Bupleurum falcatum L, protects heat-stressed pig kidney proximal tubular (LLC-PK1) cells against oxidative damage. SSd alone is not cytotoxic at concentrations of 1 or 3 μg/mL as demonstrated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To assess the effects of SSd on heat stress-induced cellular damage, LLC-PK1 cells were pretreated with various concentrations of SSd, heat stressed at 42°C for 1 h, and then returned to 37°C for 9 h. DNA ladder and MTT assays demonstrated that SSd helped to prevent heat stress-induced cellular damage when compared to untreated cells. Additionally, pretreatment with SSd increased the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) but decreased the concentration of malondialdehyde (MDA) in a dose-dependent manner when compared to controls. Furthermore, real-time PCR and Western blot analysis demonstrated that SSd significantly increased the expression of copper and zinc superoxide dismutase (SOD-1), CAT, GPx-1 and heat shock protein 72 (HSP72) at both the mRNA and protein levels. In conclusion, these results are the first to demonstrate that SSd ameliorates heat stress-induced oxidative damage by modulating the activity of anti-oxidant enzymes and HSP72 in LLC-PK1 cells.

  16. Sex as a response to oxidative stress: a twofold increase in cellular reactive oxygen species activates sex genes.

    PubMed

    Nedelcu, Aurora M; Marcu, Oana; Michod, Richard E

    2004-08-07

    Organisms are constantly subjected to factors that can alter the cellular redox balance and result in the formation of a series of highly reactive molecules known as reactive oxygen species (ROS). As ROS can be damaging to biological structures, cells evolved a series of mechanisms (e.g. cell-cycle arrest, programmed cell death) to respond to high levels of ROS (i.e. oxidative stress). Recently, we presented evidence that in a facultatively sexual lineage--the multicellular green alga Volvox carteri--sex is an additional response to increased levels of stress, and probably ROS and DNA damage. Here we show that, in V. carteri, (i) sex is triggered by an approximately twofold increase in the level of cellular ROS (induced either by the natural sex-inducing stress, namely heat, or by blocking the mitochondrial electron transport chain with antimycin A), and (ii) ROS are responsible for the activation of sex genes. As most types of stress result in the overproduction of ROS, we believe that our findings will prove to extend to other facultatively sexual lineages, which could be indicative of the ancestral role of sex as an adaptive response to stress and ROS-induced DNA damage.

  17. Increased levels of oxidative and carbonyl stress markers in normal ovarian cortex surrounding endometriotic cysts.

    PubMed

    Di Emidio, Giovanna; D'Alfonso, Angela; Leocata, Pietro; Parisse, Valentina; Di Fonso, Adina; Artini, Paolo Giovanni; Patacchiola, Felice; Tatone, Carla; Carta, Gaspare

    2014-11-01

    Many evidence support the view that endometriotic cyst may exert detrimental effect on the surrounding ovarian microenvironment so representing a risk to functionality of adjacent follicles. Patients with benign ovarian cyst (endometriotic, follicular and dermoid cysts) subjected to laparoscopic cystectomy were enrolled in the present retrospective study in order to analyze whether endometriotic tissue could negatively affect the surrounding normal ovarian cortex more severely than other ovarian cysts. To this end we carried out immunohistochemistry analysis and comparative determination of the transcription factor FOXO3A, oxidized DNA adduct 8-OHdG (8-hydroxy-2'-deoxyguanosine) and damaged proteins known as AGEs (Advanced Glycation End products) as markers of ovarian stress response and molecular damage. Our results show that all the markers analyzed were present in normal ovarian tissue surrounding benign cysts. We observed higher levels of FOXO3A (15.90 ± 0.28), 8-OHdG (13.33 ± 2.07) and AGEs (12.58 ± 4.34) staining in normal ovarian cortex surrounding endometriotic cysts in comparison with follicular cysts (9.04 ± 0.29, 2.67 ± 2.67, 11.31 ± 2.95, respectively) and dermoid cysts (2.02 ± 0.18, 4.33 ± 2.58 and 10.56 ± 4.03, respectively). These results provide evidence that ovarian endometrioma is responsible for more severe alterations to cellular biomolecules than follicular and dermoid cysts.

  18. Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus*

    PubMed Central

    Douglas, Donna N.; Pu, Christopher Hao; Lewis, Jamie T.; Bhat, Rakesh; Anwar-Mohamed, Anwar; Logan, Michael; Lund, Garry; Addison, William R.; Lehner, Richard; Kneteman, Norman M.

    2016-01-01

    Cytopathic effects are currently believed to contribute to hepatitis C virus (HCV)-induced liver injury and are readily observed in Huh7.5 cells infected with the JFH-1 HCV strain, manifesting as apoptosis highly correlated with growth arrest. Reactive oxygen species, which are induced by HCV infection, have recently emerged as activators of AMP-activated protein kinase. The net effect is ATP conservation via on/off switching of metabolic pathways that produce/consume ATP. Depending on the scenario, this can have either pro-survival or pro-apoptotic effects. We demonstrate reactive oxygen species-mediated activation of AMP-activated kinase in Huh7.5 cells during HCV (JFH-1)-induced growth arrest. Metabolic labeling experiments provided direct evidence that lipid synthesis is attenuated, and β-oxidation is enhanced in these cells. A striking increase in nuclear peroxisome proliferator-activated receptor α, which plays a dominant role in the expression of β-oxidation genes after ligand-induced activation, was also observed, and we provide evidence that peroxisome proliferator-activated receptor α is constitutively activated in these cells. The combination of attenuated lipid synthesis and enhanced β-oxidation is not conducive to lipid accumulation, yet cellular lipids still accumulated during this stage of infection. Notably, the serum in the culture media was the only available source for polyunsaturated fatty acids, which were elevated (2-fold) in the infected cells, implicating altered lipid import/export pathways in these cells. This study also provided the first in vivo evidence for enhanced β-oxidation during HCV infection because HCV-infected SCID/Alb-uPA mice accumulated higher plasma ketones while fasting than did control mice. Overall, this study highlights the reprogramming of hepatocellular lipid metabolism and bioenergetics during HCV infection, which are predicted to impact both the HCV life cycle and pathogenesis. PMID:26627833

  19. Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus.

    PubMed

    Douglas, Donna N; Pu, Christopher Hao; Lewis, Jamie T; Bhat, Rakesh; Anwar-Mohamed, Anwar; Logan, Michael; Lund, Garry; Addison, William R; Lehner, Richard; Kneteman, Norman M

    2016-01-22

    Cytopathic effects are currently believed to contribute to hepatitis C virus (HCV)-induced liver injury and are readily observed in Huh7.5 cells infected with the JFH-1 HCV strain, manifesting as apoptosis highly correlated with growth arrest. Reactive oxygen species, which are induced by HCV infection, have recently emerged as activators of AMP-activated protein kinase. The net effect is ATP conservation via on/off switching of metabolic pathways that produce/consume ATP. Depending on the scenario, this can have either pro-survival or pro-apoptotic effects. We demonstrate reactive oxygen species-mediated activation of AMP-activated kinase in Huh7.5 cells during HCV (JFH-1)-induced growth arrest. Metabolic labeling experiments provided direct evidence that lipid synthesis is attenuated, and β-oxidation is enhanced in these cells. A striking increase in nuclear peroxisome proliferator-activated receptor α, which plays a dominant role in the expression of β-oxidation genes after ligand-induced activation, was also observed, and we provide evidence that peroxisome proliferator-activated receptor α is constitutively activated in these cells. The combination of attenuated lipid synthesis and enhanced β-oxidation is not conducive to lipid accumulation, yet cellular lipids still accumulated during this stage of infection. Notably, the serum in the culture media was the only available source for polyunsaturated fatty acids, which were elevated (2-fold) in the infected cells, implicating altered lipid import/export pathways in these cells. This study also provided the first in vivo evidence for enhanced β-oxidation during HCV infection because HCV-infected SCID/Alb-uPA mice accumulated higher plasma ketones while fasting than did control mice. Overall, this study highlights the reprogramming of hepatocellular lipid metabolism and bioenergetics during HCV infection, which are predicted to impact both the HCV life cycle and pathogenesis. © 2016 by The American Society

  20. Increased tolerance to salt stress in OPDA-deficient rice ALLENE OXIDE CYCLASE mutants is linked to an increased ROS-scavenging activity

    PubMed Central

    Hazman, Mohamed; Hause, Bettina; Eiche, Elisabeth; Nick, Peter; Riemann, Michael

    2015-01-01

    Salinity stress represents a global constraint for rice, the most important staple food worldwide. Therefore the role of the central stress signal jasmonate for the salt response was analysed in rice comparing the responses to salt stress for two jasmonic acid (JA) biosynthesis rice mutants (cpm2 and hebiba) impaired in the function of ALLENE OXIDE CYCLASE (AOC) and their wild type. The aoc mutants were less sensitive to salt stress. Interestingly, both mutants accumulated smaller amounts of Na+ ions in their leaves, and showed better scavenging of reactive oxygen species (ROS) under salt stress. Leaves of the wild type and JA mutants accumulated similar levels of abscisic acid (ABA) under stress conditions, and the levels of JA and its amino acid conjugate, JA–isoleucine (JA-Ile), showed only subtle alterations in the wild type. In contrast, the wild type responded to salt stress by strong induction of the JA precursor 12-oxophytodienoic acid (OPDA), which was not observed in the mutants. Transcript levels of representative salinity-induced genes were induced less in the JA mutants. The absence of 12-OPDA in the mutants correlated not only with a generally increased ROS-scavenging activity, but also with the higher activity of specific enzymes in the antioxidative pathway, such as glutathione S-transferase, and fewer symptoms of damage as, for example, indicated by lower levels of malondialdehyde. The data are interpreted in a model where the absence of OPDA enhanced the antioxidative power in mutant leaves. PMID:25873666

  1. Increased tolerance to salt stress in OPDA-deficient rice ALLENE OXIDE CYCLASE mutants is linked to an increased ROS-scavenging activity.

    PubMed

    Hazman, Mohamed; Hause, Bettina; Eiche, Elisabeth; Nick, Peter; Riemann, Michael

    2015-06-01

    Salinity stress represents a global constraint for rice, the most important staple food worldwide. Therefore the role of the central stress signal jasmonate for the salt response was analysed in rice comparing the responses to salt stress for two jasmonic acid (JA) biosynthesis rice mutants (cpm2 and hebiba) impaired in the function of ALLENE OXIDE CYCLASE (AOC) and their wild type. The aoc mutants were less sensitive to salt stress. Interestingly, both mutants accumulated smaller amounts of Na(+) ions in their leaves, and showed better scavenging of reactive oxygen species (ROS) under salt stress. Leaves of the wild type and JA mutants accumulated similar levels of abscisic acid (ABA) under stress conditions, and the levels of JA and its amino acid conjugate, JA-isoleucine (JA-Ile), showed only subtle alterations in the wild type. In contrast, the wild type responded to salt stress by strong induction of the JA precursor 12-oxophytodienoic acid (OPDA), which was not observed in the mutants. Transcript levels of representative salinity-induced genes were induced less in the JA mutants. The absence of 12-OPDA in the mutants correlated not only with a generally increased ROS-scavenging activity, but also with the higher activity of specific enzymes in the antioxidative pathway, such as glutathione S-transferase, and fewer symptoms of damage as, for example, indicated by lower levels of malondialdehyde. The data are interpreted in a model where the absence of OPDA enhanced the antioxidative power in mutant leaves.

  2. Chronic oxidative stress increases the integration frequency of foreign DNA and human papillomavirus 16 in human keratinocytes

    PubMed Central

    Chen Wongworawat, Yan; Filippova, Maria; Williams, Vonetta M; Filippov, Valery; Duerksen-Hughes, Penelope J

    2016-01-01

    Cervical cancer is the second most common cancer, and the fourth most common cause of cancer death in women worldwide. Nearly all of these cases are caused by high-risk HPVs (HR HPVs), of which HPV16 is the most prevalent type. In most cervical cancer specimens, HR HPVs are found integrated into the human genome, indicating that integration is a key event in cervical tumor development. An understanding of the mechanisms that promote integration may therefore represent a unique opportunity to intercept carcinogenesis. To begin identifying these mechanisms, we tested the hypothesis that chronic oxidative stress (OS) induced by virus- and environmentallymediated factors can induce DNA damage, and thereby increase the frequency with which HPV integrates into the host genome. We found that virus-mediated factors are likely involved, as expression of E6*, a splice isoform of HPV16 E6, increased the levels of reactive oxygen species (ROS), caused oxidative DNA damage, and increased the frequency of plasmid DNA integration as assessed by colony formation assays. To assess the influence of environmentally induced chronic OS, we used L-Buthionine-sulfoximine (BSO) to lower the level of the intracellular antioxidant glutathione. Similar to our observations with E6*, glutathione depletion by BSO also increased ROS levels, caused oxidative DNA damage and increased the integration frequency of plasmid DNA. Finally, under conditions of chronic OS, we were able to induce and characterize a few independent events in which episomal HPV16 integrated into the host genome of cervical keratinocytes. Our results support a chain of events leading from induction of oxidative stress, to DNA damage, to viral integration, and ultimately to carcinogenesis. PMID:27186429

  3. The adaptogens rhodiola and schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol.

    PubMed

    Panossian, Alexander; Hambardzumyan, Marina; Hovhanissyan, Areg; Wikman, Georg

    2007-01-01

    Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E(2), leukotriene B(4) and thromboxane B(2) were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the final treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200-300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their antidepressant activity as well as their positive effects on mental performance under stress.

  4. The Adaptogens Rhodiola and Schizandra Modify the Response to Immobilization Stress in Rabbits by Suppressing the Increase of Phosphorylated Stress-activated Protein Kinase, Nitric Oxide and Cortisol

    PubMed Central

    Panossian, Alexander; Hambardzumyan, Marina; Hovhanissyan, Areg; Wikman, Georg

    2007-01-01

    Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E2, leukotriene B4 and thromboxane B2 were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the final treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200–300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their antidepressant activity as well as their positive effects on mental performance under stress. PMID:21901061

  5. Plgf-/-eNos-/- mice show defective angiogenesis associated with increased oxidative stress in response to tissue ischemia.

    PubMed

    Gigante, Bruna; Morlino, Giulia; Gentile, Maria Teresa; Persico, Maria Graziella; De Falco, Sandro

    2006-05-01

    Neo-angiogenesis is a complex phenomenon modulated by the concerted action of several molecular factors. We have generated a congenic line of knockout mice carrying null mutations of both placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS), two genes that play a pivotal role in the regulation of pathological angiogenesis. In the present study, we describe the phenotype of this new experimental animal model after surgically induced hind-limb ischemia. Plgf-/-, eNos-/-, Plgf-/- eNos-/-, and wild-type C57BL/6J mice were studied. Plgf-/- eNos-/- mice showed the most severe phenotype: self-amputation, and death occurred in up to 47% of the animals studied; in ischemic legs, capillary density was severely reduced; macrophage infiltration and oxidative stress increased as compared to the other groups of animals. These changes were associated with an up-regulation of both inducible NOS (iNOS) expression and vascular endothelial growth factor (VEGF) protein levels in ischemic limbs, and to an increased extent of protein nitration. Our results demonstrate that the deletion of these two genes, Plgf, which acts in synergism with VEGF, and eNos, a downstream mediator of VEGF, determines a significant change in the vascular response to an ischemic stimulus and that oxidative stress within the ischemic tissue represents a crucial factor to maintain tissue homeostasis.

  6. Effects of increased temperature on metabolic activity and oxidative stress in the first life stages of marble trout (Salmo marmoratus).

    PubMed

    Simčič, Tatjana; Jesenšek, Dušan; Brancelj, Anton

    2015-08-01

    Climate change may result in future alterations in thermal regime which could markedly affect the early developmental stages of cold water fish due to their expected high sensitivity to increasing temperature. In the present study, the effect of temperature increase of 2, 4 and 6°C on the oxygen consumption rate (R), the activity of respiratory electron transport system (ETS) and oxidative stress have been studied in four developmental stages of the marble trout (Salmo marmoratus)-eyed eggs, yolk-sac larvae and juveniles of 1 and 3 months. Oxygen consumption rate and ETS activity increased with level of development and with temperature in all four stages. ETS/R ratios decreased during development and correlated with temperature in eyed eggs, larvae and juveniles of 1 month, but not in juveniles of 3 months. Low ETS/R ratios at higher temperatures indicate stress response in eyed eggs, the most temperature sensitive developmental stage. Catalase (CAT) and glutathione reductase (GR) activities increased during development, but responded differently to elevated temperature in the different developmental stages. Stress in eyed eggs, caused by higher temperatures, resulted in increased oxygen consumption rate and increased activities of CAT and GR. Larvae were sensitive to increased temperature only at the highest experimental temperature of 16°C. Increased temperature did not stress the metabolism of the juveniles, since they were able to compensate their metabolic activity. The earlier developmental stages of marble trout are thus more sensitive to temperature increase than juveniles and therefore more endangered by higher water temperatures. This is the first report connecting oxygen consumption, ETS activity and ETS/R ratio with the activities of antioxidant enzymes in relation to increased temperature in salmonids.

  7. Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases Lifespan in Caenorhabditis elegans

    PubMed Central

    Grompone, Gianfranco; Martorell, Patricia; Llopis, Silvia; González, Núria; Genovés, Salvador; Mulet, Ana Paula; Fernández-Calero, Tamara; Tiscornia, Inés; Bollati-Fogolín, Mariela; Chambaud, Isabelle; Foligné, Benoit; Montserrat, Agustín; Ramón, Daniel

    2012-01-01

    Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3 mM and 5 mM H2O2). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans. PMID:23300685

  8. Oxidized LDL-Exposed Human Macrophages Display Increased MMP-9 Expression and Secretion Mediated by Endoplasmic Reticulum Stress.

    PubMed

    Sanda, Gabriela M; Deleanu, Mariana; Toma, Laura; Stancu, Camelia S; Simionescu, Maya; Sima, Anca V

    2017-04-01

    Oxidatively modified low-density lipoproteins (oxLDL) alter the proper function of the endoplasmic reticulum (ER), inducing ER stress (ERS), which consequently activates inflammatory pathways in macrophages. Matrix metalloproteinase-9 (MMP-9) is the main protease acting on the degradation of the extracellular matrix and the ensuing destabilization of the atherosclerotic plaque. We aimed to investigate whether ERS induced by oxLDL or tunicamycin (TM) in human macrophages is associated with the stimulation of MMP-9 expression and secretion. The results showed that oxLDL induced in THP-1 macrophages: (i) increase of MMP-9 gene expression and its pro-form secretion, (ii) intracellular accumulation of 7-ketocholesterol, (iii) ERS activation (increased eIF2α phosphorylation, XBP1 and CHOP mRNA levels, and Grp78 protein expression), and (iv) oxidative stress (increased levels of reactive oxygen species and NADPH oxidase activity). Incubation of macrophages with ERS inducer, TM determined the secretion of both pro- and active-form of MMP-9 and oxidative stress. Treatment of oxLDL or TM-incubated cells with ERS inhibitor, sodium phenylbutyrate decreased MMP-9 gene expression, secretion, and activity. The inhibitor of NADPH oxidase, apocynin, decreased XBP-1 and CHOP mRNA levels, and MMP-9 gene expression and secretion in oxLDL-exposed cells. In conclusion, oxLDL stimulate MMP-9 expression and secretion in human macrophages by mechanisms involving ERS. J. Cell. Biochem. 118: 661-669, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Increased oxidative stress in human fetal membranes overlying the cervix from term non-labouring and post labour deliveries.

    PubMed

    Chai, M; Barker, G; Menon, R; Lappas, M

    2012-08-01

    Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects the amnion and chorion layers of the fetal membranes is one of the key events leading to rupture of membranes. Oxidant stress caused by increased formation of reactive oxygen species and/or reduced antioxidant capacity may predispose to membrane rupture, a major cause of preterm birth. The aim of this study was to determine the effect of human labour and supracervical (SC) apposition on antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To determine the effect of human labour on oxidative stress status, fetal membranes from the SC site (SCS) were collected from women at term Caesarean section (no labour), and from the site of membrane rupture (SOR) after spontaneous labour onset and delivery (post labour). To determine the effect of SC apposition on oxidative stress status, amnion was collected from the SCS and a distal site (DS) in women at term Caesarean section in the absence of labour. The release of 8-isoprostane was significantly higher in amnion from the SCS compared to DS, and in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were lower in amnion from the SC compared to DS. SOD gene expression and enzyme activity were lower in fetal membranes after labour. There was no difference in expression or activity in catalase, GPx and glutathione reductase (GSR) between no labour and post labour fetal membranes. In primary amnion cells, SOD supplementation significantly augmented IL-1β induced MMP-9 expression and activity. In summary, non-labouring SC fetal membranes are characterised by reduced antioxidant enzyme activity when compared to distal membranes, and, as such, may be more susceptible to oxidative damage and thus membrane rupture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Enriching the drinking water of rats with extracts of Salvia officinalis and Thymus vulgaris increases their resistance to oxidative stress.

    PubMed

    Horváthová, Eva; Srančíková, Annamária; Regendová-Sedláčková, Eva; Melušová, Martina; Meluš, Vladimír; Netriová, Jana; Krajčovičová, Zdenka; Slameňová, Darina; Pastorek, Michal; Kozics, Katarína

    2016-01-01

    Nature is an attractive source of therapeutic compounds. In comparison to the artificial drugs, natural compounds cause less adverse side effects and are suitable for current molecularly oriented approaches to drug development and their mutual combining. Medicinal plants represent one of the most available remedy against various diseases. Proper examples are Salvia officinalis L. and Thymus vulgaris L. which are known aromatic medicinal plants. They are very popular and frequently used in many countries. The molecular mechanism of their biological activity has not yet been fully understood. The aim of this study was to ascertain if liver cells of experimental animals drinking extracts of sage or thyme will manifest increased resistance against oxidative stress. Adult Sprague-Dawley rats were divided into seven groups. They drank sage or thyme extracts for 2 weeks. At the end of the drinking period, blood samples were collected for determination of liver biochemical parameters and hepatocytes were isolated to analyze (i) oxidatively generated DNA damage (conventional and modified comet assay), (ii) activities of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and (iii) content of glutathione. Intake of sage and thyme had no effect either on the basal level of DNA damage or on the activity of SOD in rat hepatocytes and did not change the biochemical parameters of blood plasma. Simultaneously, the activity of GPx was significantly increased and the level of DNA damage induced by oxidants was decreased. Moreover, sage extract was able to start up the antioxidant protection expressed by increased content of glutathione. Our results indicate that the consumption of S.officinalis and T.vulgaris extracts positively affects resistency of rat liver cells against oxidative stress and may have hepatoprotective potential.

  11. Nanocerium oxide increases the survival of adult rod and cone photoreceptor in culture by abrogating hydrogen peroxide-induced oxidative stress.

    PubMed

    Bhargava, Neelima; Shanmugaiah, Vellasamy; Saxena, Manav; Sharma, Manish; Sethy, Niroj Kumar; Singh, Sushil Kumar; Balakrishnan, Karuppiah; Bhargava, Kalpana; Das, Mainak

    2016-09-16

    In vitro cell culture system for adult rod and cone photoreceptor (PR) is an effective and economical model for screening drug candidates against all kinds of age related retinal blindness. Interestingly, adult PR cells have a limited survival in the culture system, thus preventing full exploitation of this in vitro approach for drug screening applications. The limited survival of the adult PR cells in culture is due to their inherently high oxidative stress and photic injury. Mixed valence-state ceria nanoparticles have the ability to scavenge free radicals and reduce oxidative stress. Here, ceria nanoparticles of 5-10 nm dimensions have been synthesized, possessing dual oxidation state (+3 and +4) as evident from x-ray photoelectron spectroscopy and exhibiting real time reduction of hydrogen peroxide (H2O2) as quantified by absorbance spectroscopy and cyclic voltammogram analysis. Using flow cytometry and cell culture assay, it has been shown that, upon one time addition of 10 nM of nanoceria in the PR culture of the 18 months old adult common carp (Cyprinus carpio) at the time of plating the cells, the oxidative stress caused due to hydrogen peroxide assault could be abrogated. A further single application of nanoceria significantly increases the survival of these fragile cells in the culture, thus paving way for developing a more robust photoreceptor culture model to study the aging photoreceptor cells in a defined condition.

  12. Markers of oxidative stress are increased in exhaled breath condensates of children with atopic dermatitis.

    PubMed

    Peroni, D G; Bodini, A; Corradi, M; Coghi, A; Boner, A L; Piacentini, G L

    2012-04-01

    Airway inflammation may be present in subjects affected by atopic dermatitis (AD) but still without asthma symptoms. Exhaled breath condensate (EBC) reflects the composition of bronchoalveolar extracellular lining fluid that contains a large number of mediators of airway inflammation and oxidative damage.   We assessed inflammatory markers in the EBC of patients with AD. Fifty-six children (34 girls and 22 boys) were enrolled: 33 affected by AD and 23 healthy controls.   EBC was collected using a condenser device. We measured EBC pH and concentrations of leukotriene B4 (LTB4), 8-isoprostane, H(2) O(2) , malondialdehyde and 4-hydroxynoneal. Respiratory resistance was also evaluated.   EBC pH in patients with AD was significantly lower than in healthy children, median (range) being 8·02 (7·94-8·12) in AD vs. 8·11 (8·05-8·16) (P = 0·02). The values of exhaled 8-isoprostane and LTB4 were significantly increased in subjects with AD compared with normal controls (P < 0·01 and P < 0·001, respectively). There was increased 4-hydroxynoneal in patients with AD but this did not reach statistical significance. Evaluating respiratory resistance, no bronchoreversibility was demonstrated in the children with AD. pH, LTB4 and 8-isoprostane in EBC could be sensitive markers of airway inflammation in children with AD. Prospective studies would be of interest to evaluate if airway inflammation, not yet clinically evident, could predict the development of asthma later in life in children with AD. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  13. Fenofibrate Improves Vascular Endothelial Function by Reducing Oxidative Stress While Increasing eNOS in Healthy Normolipidemic Older Adults

    PubMed Central

    Walker, Ashley E; Kaplon, Rachelle E; Lucking, Sara Marian S; Russell-Nowlan, Molly J; Eckel, Robert H; Seals, Douglas R

    2013-01-01

    Vascular endothelial dysfunction develops with aging, as indicated by impaired endothelium-dependent dilation(EDD), and is related to increased cardiovascular disease risk. We hypothesized that short-term treatment with fenofibrate, a lipid-lowering agent with potential pleiotropic effects, would improve EDD in middle-aged and older normolipidemic adults by reducing oxidative stress. Brachial artery flow-mediated dilation (FMD), a measure of EDD, was assessed in 22healthy adults aged 50-77 years before and after 7days of fenofibrate (145 mg/d; n=12/7M) or placebo (n=10/5M). Brachial FMD was unchanged with placebo, but improved after 2 and 7 days of fenofibrate (5.1±0.7 vs. 2d: 6.0±0.7 and 7d: 6.4±0.6 %Δ; both P<0.005). The improvements in FMD after 7 days remained significant (P<0.05) after accounting for modest changes in plasma total and LDL-cholesterol. Endothelium-independent dilation was not affected by fenofibrate or placebo (P>0.05). Infusion (i.v.) of the antioxidant vitamin C improved brachial FMD at baseline in both groups and during placebo treatment (P<0.05), but not after 2 and 7 days of fenofibrate (P>0.05). Fenofibrate treatment also reduced plasma oxidized LDL, a systemic marker of oxidative stress, compared with placebo (P<0.05). In vascular endothelial cells sampled from peripheral veins of the subjects, endothelial nitric oxide synthase (eNOS) protein expression was unchanged with placebo and after 2 days of fenofibrate, but was increased after 7 days of fenofibrate (0.54±0.03 vs. 2d: 0.52±0.04 and 7d: 0.76±0.11 intensity/HUVEC control; P<0.05 7d). Short-term treatment with fenofibrate improves vascular endothelial function in healthy normolipidemic middle-aged/older adults by reducing oxidative stress and induces increases in eNOS. PMID:23108655

  14. Vitamin B6 deficient plants display increased sensitivity to high light and photo-oxidative stress

    PubMed Central

    Havaux, Michel; Ksas, Brigitte; Szewczyk, Agnieszka; Rumeau, Dominique; Franck, Fabrice; Caffarri, Stefano; Triantaphylidès, Christian

    2009-01-01

    Background Vitamin B6 is a collective term for a group of six interconvertible compounds: pyridoxine, pyridoxal, pyridoxamine and their phosphorylated derivatives. Vitamin B6 plays essential roles as a cofactor in a range of biochemical reactions. In addition, vitamin B6 is able to quench reactive oxygen species in vitro, and exogenously applied vitamin B6 protects plant cells against cell death induced by singlet oxygen (1O2). These results raise the important question as to whether plants employ vitamin B6 as an antioxidant to protect themselves against reactive oxygen species. Results The pdx1.3 mutation affects the vitamin B6 biosynthesis enzyme, pyridoxal synthase (PDX1), and leads to a reduction of the vitamin B6 concentration in Arabidopsis thaliana leaves. Although leaves of the pdx1.3 Arabidopsis mutant contained less chlorophyll than wild-type leaves, we found that vitamin B6 deficiency did not significantly impact photosynthetic performance or shoot and root growth. Chlorophyll loss was associated with an increase in the chlorophyll a/b ratio and a selective decrease in the abundance of several PSII antenna proteins (Lhcb1/2, Lhcb6). These changes were strongly dependent on light intensity, with high light amplifying the difference between pdx1.3 and the wild type. When leaf discs were exposed to exogenous 1O2, lipid peroxidation in pdx1.3 was increased relative to the wild type; this effect was not observed with superoxide or hydrogen peroxide. When leaf discs or whole plants were exposed to excess light energy, 1O2-mediated lipid peroxidation was enhanced in leaves of the pdx1.3 mutant relative to the wild type. High light also caused an increased level of 1O2 in vitamin B6-deficient leaves. Combining the pdx1.3 mutation with mutations affecting the level of 'classical' quenchers of 1O2 (zeaxanthin, tocopherols) resulted in a highly photosensitive phenotype. Conclusion This study demonstrates that vitamin B6 has a function in the in vivo antioxidant

  15. Vitamin B6 deficient plants display increased sensitivity to high light and photo-oxidative stress.

    PubMed

    Havaux, Michel; Ksas, Brigitte; Szewczyk, Agnieszka; Rumeau, Dominique; Franck, Fabrice; Caffarri, Stefano; Triantaphylidès, Christian

    2009-11-10

    Vitamin B6 is a collective term for a group of six interconvertible compounds: pyridoxine, pyridoxal, pyridoxamine and their phosphorylated derivatives. Vitamin B6 plays essential roles as a cofactor in a range of biochemical reactions. In addition, vitamin B6 is able to quench reactive oxygen species in vitro, and exogenously applied vitamin B6 protects plant cells against cell death induced by singlet oxygen (1O2). These results raise the important question as to whether plants employ vitamin B6 as an antioxidant to protect themselves against reactive oxygen species. The pdx1.3 mutation affects the vitamin B6 biosynthesis enzyme, pyridoxal synthase (PDX1), and leads to a reduction of the vitamin B6 concentration in Arabidopsis thaliana leaves. Although leaves of the pdx1.3 Arabidopsis mutant contained less chlorophyll than wild-type leaves, we found that vitamin B6 deficiency did not significantly impact photosynthetic performance or shoot and root growth. Chlorophyll loss was associated with an increase in the chlorophyll a/b ratio and a selective decrease in the abundance of several PSII antenna proteins (Lhcb1/2, Lhcb6). These changes were strongly dependent on light intensity, with high light amplifying the difference between pdx1.3 and the wild type. When leaf discs were exposed to exogenous 1O2, lipid peroxidation in pdx1.3 was increased relative to the wild type; this effect was not observed with superoxide or hydrogen peroxide. When leaf discs or whole plants were exposed to excess light energy, 1O2-mediated lipid peroxidation was enhanced in leaves of the pdx1.3 mutant relative to the wild type. High light also caused an increased level of 1O2 in vitamin B6-deficient leaves. Combining the pdx1.3 mutation with mutations affecting the level of 'classical' quenchers of 1O2 (zeaxanthin, tocopherols) resulted in a highly photosensitive phenotype. This study demonstrates that vitamin B6 has a function in the in vivo antioxidant defense of plants. Thus, the

  16. Increased vitamin E content in the lung after ozone exposure: A possible mobilization in response to oxidative stress

    SciTech Connect

    Elsayed, N.M.; Mustafa, M.G.; Mead, J.F. )

    1990-11-01

    Vitamin E (vE) is a biological free radical scavenger capable of providing antioxidant protection depending upon its tissue content. In previous studies, we observed that vE increased significantly in rat lungs after oxidant exposure, and we postulated that vE may be mobilized to the lung from other body sites under oxidative stress. To test this hypothesis, we fed Long-Evans rats either a vE-supplemented or a vE-deficient diet, injected them intraperitoneally with 14C-labeled vE, and then exposed half of each group to 0.5 ppm ozone (O3) for 5 days. After exposure, we determined vE content and label retention in lungs, liver, kidney, heart, brain, plasma, and white adipose tissue. Tissue vE content of all tissues generally reflected the dietary level, but labeled vE retention in all tissues was inversely related to tissue content, possibly reflecting a saturation of existing vE receptor sites in supplemented rats. Following O3 exposure, lung vE content increased significantly in supplemented rats and decreased in deficient rats, but the decrease was not statistically significant, and vE content remained unchanged in all other tissues of both dietary groups. Retention of 14C-labeled vE increased in all tissues of O3-exposed rats of both dietary groups, except in vE-deficient adipose tissue and vE-supplemented brain, where it decreased, and plasma, where it did not change. The marked increases in lung vE content and labeled vE retention of O3-exposed vE-supplemented rats support our hypothesis that vE may be mobilized to the lung in response to oxidative stress, providing that the vitamin is sufficiently available in other body sites.

  17. High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes.

    PubMed

    Thilo, Florian; Lee, Marlene; Xia, Shengqiang; Zakrzewicz, Andreas; Tepel, Martin

    2014-07-18

    Transient receptor potential canonical (TRPC) channels type 6 play an important role in the function of human podocytes. Diabetic nephropathy is characterized by altered TRPC6 expression and functions of podocytes. Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes. Human podocytes were exposed to control conditions (5.6 mmol/L D-glucose), high glucose (30 mmol/L D-glucose or L-glucose), 100 μmol/L peroxynitrite, or high glucose and the superoxide dismutase mimetic tempol (100 μmol/L). TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay. Intracellular reactive oxygen species (ROS) and cytosolic calcium were measured using fluorescent dye techniques. High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p<0.05) and TRPC6 protein expression to 1.44±0.07 (p<0.05) without altering SDC-4 transcripts or protein expression. The D-glucose induced increase of TRPC6 expression was blocked by tempol. Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p<0.05) and TRPC6 protein expression to 1.28±0.05 (p<0.05) without altering SDC-4 transcripts or protein expression. In human podocytes transfected with scrambled siRNA, high D-glucose increased ROS after 90 min to 3.55±0.08 arbitrary units while 5.6 mmol/L D-glucose increased ROS to 2.49±0.09 (p<0.001) only. The increase in ROS was inhibited by tempol and by SDC-4 knockdown. High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes.

  18. High-Fat Diet Increased Renal and Hepatic Oxidative Stress Induced by Vanadium of Wistar Rat.

    PubMed

    Wang, J P; Cui, R Y; Zhang, K Y; Ding, X M; Luo, Y H; Bai, S P; Zeng, Q F; Xuan, Y; Su, Z W

    2016-04-01

    The study was conducted to assess the effect of vanadium (V) in high-fat diet on the liver and kidney of rats in a 5-week trial. Seventy-two female Wistar rats (BW = 95 ± 5 g) were randomly allotted into eight groups. Groups I, II, III, and IV obtained low-fat diet containing 0, 3, 15, and 30 mg/kg V, and V, VI, VII, and VIII groups received the respective vanadium doses with high-fat diet, respectively. There were lesions in the liver and kidney of V, VI, VII, and VIII groups, granular degeneration and vacuolar degeneration were observed in the renal tubular and glomerulus epithelial cells, and hepatocytes showed granular degeneration and vacuolar degeneration. Supplemented high-fat diet with vanadium was shown to decrease (P < 0.05) activities of superoxide dismutase, total antioxidant capacity, glutathione-S transferase, and NAD(P)H/quinone oxidoreductase 1 (NQO1) and increase malondialdehyde content in the liver and kidney. The relative expression of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and NQO1 mRNA was downregulated by V addition and high-fat diet, and the effect of V was more pronounced in high-fat diet (interaction, P < 0.05), with VIII group having the lowest mRNA expression of Nrf-2 and NQO1 in the liver and kidney. In conclusion, it suggested that dietary vanadium ranging from 15 to 30 mg/kg could lead to oxidative damage and vanadium accumulation in the liver and kidney, which caused renal and hepatic toxicity. The high-fat diet enhanced vanadium-induced hepatic and renal damage, and the mechanism was related to the modulation of the hepatic and renal mRNA expression of Nrf-2 and NQO1.

  19. BRCA1 and Oxidative Stress

    PubMed Central

    Yi, Yong Weon; Kang, Hyo Jin; Bae, Insoo

    2014-01-01

    The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. Oxidative stress caused by reactive oxygen species (ROS) is implicated in carcinogenesis and is used strategically to treat human cancer. Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, we briefly summarize BRCA1’s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers. PMID:24704793

  20. Genistein induces estrogen-like effects in ovariectomized rats but fails to increase cardiac GLUT4 and oxidative stress.

    PubMed

    Al-Nakkash, Layla; Markus, Brandon; Batia, Lyn; Prozialeck, Walter C; Broderick, Tom L

    2010-12-01

    This study aimed to determine whether a 2-week genistein treatment induced estrogen-like effects in ovariectomized (OVX) Sprague-Dawley rats, after 2 weeks of subcutaneous genistein injections (250 mg/kg of body weight/day). Uterine weight, uterine-to-body weight ratio, femur weight, and femur-to-body weight ratio were all significantly increased with genistein in OVX rats. Body weight was significantly decreased with genistein in OVX rats. Genistein had no effect on the weights of heart, heart-to-body ratio, and fat pad but significantly decreased heart rate and pulse pressure. Genistein had no effect on cardiac GLUT4 protein, oxidative stress, plasma glucose, nonesterified fatty acids, or low-density lipoprotein levels; however, plasma insulin levels were significantly increased. Our results show that a 2-week genistein treatment produced favorable estrogen-like effects on some physical and physiological characteristics in OVX rats. However, based on our experimental conditions, the effects of genistein were not associated with changes in cardiac GLUT4 or oxidative stress.

  1. Ectopic Expression of a Horseradish Peroxidase Enhances Growth Rate and Increases Oxidative Stress Resistance in Hybrid Aspen

    PubMed Central

    Kawaoka, Akiyoshi; Matsunaga, Etsuko; Endo, Saori; Kondo, Shinkichi; Yoshida, Kazuya; Shinmyo, Atsuhiko; Ebinuma, Hiroyasu

    2003-01-01

    We previously demonstrated that overexpression of the horseradish (Armoracia rusticana) peroxidase prxC1a gene stimulated the growth rate of tobacco (Nicotiana tabacum) plants. Here, the cauliflower mosaic virus 35S::prxC1a construct was introduced into hybrid aspen (Populus sieboldii × Populus grandidentata). The growth rate of these transformed hybrid aspen plants was substantially increased under greenhouse conditions. The average stem length of transformed plants was 25% greater than that of control plants. There was no other obvious phenotypic difference between the transformed and control plants. Fast-growing transformed hybrid aspen showed high levels of expression of prxC1a and had elevated peroxidase activities toward guaiacol and ascorbate. However, there was no increase of the endogenous class I ascorbate peroxidase activities in the transformed plants by separate assay and activity staining of native polyacrylamide gel electrophoresis. Furthermore, calli derived from the transformed hybrid aspen grew faster than those from control plants and were resistant to the oxidative stress imposed by hydrogen peroxide. Therefore, enhanced peroxidase activity affects plant growth rate and oxidative stress resistance. PMID:12857800

  2. Genistein Induces Estrogen-Like Effects in Ovariectomized Rats but Fails to Increase Cardiac GLUT4 and Oxidative Stress

    PubMed Central

    Markus, Brandon; Batia, Lyn; Prozialeck, Walter C.; Broderick, Tom L.

    2010-01-01

    Abstract This study aimed to determine whether a 2-week genistein treatment induced estrogen-like effects in ovariectomized (OVX) Sprague-Dawley rats, after 2 weeks of subcutaneous genistein injections (250 mg/kg of body weight/day). Uterine weight, uterine-to-body weight ratio, femur weight, and femur-to-body weight ratio were all significantly increased with genistein in OVX rats. Body weight was significantly decreased with genistein in OVX rats. Genistein had no effect on the weights of heart, heart-to-body ratio, and fat pad but significantly decreased heart rate and pulse pressure. Genistein had no effect on cardiac GLUT4 protein, oxidative stress, plasma glucose, nonesterified fatty acids, or low-density lipoprotein levels; however, plasma insulin levels were significantly increased. Our results show that a 2-week genistein treatment produced favorable estrogen-like effects on some physical and physiological characteristics in OVX rats. However, based on our experimental conditions, the effects of genistein were not associated with changes in cardiac GLUT4 or oxidative stress. PMID:20954809

  3. LPS from P. gingivalis and Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis

    PubMed Central

    Gölz, L.; Memmert, S.; Rath-Deschner, B.; Jäger, A.; Appel, T.; Baumgarten, G.; Götz, W.; Frede, S.

    2014-01-01

    Oxidative stress is characterized by an accumulation of reactive oxygen species (ROS) and plays a key role in the progression of inflammatory diseases. We hypothesize that hypoxic and inflammatory events induce oxidative stress in the periodontal ligament (PDL) by activating NOX4. Human primary PDL fibroblasts were stimulated with lipopolysaccharide from Porphyromonas gingivalis (LPS-PG), a periodontal pathogen bacterium under normoxic and hypoxic conditions. By quantitative PCR, immunoblot, immunostaining, and a specific ROS assay we determined the amount of NOX4, ROS, and several redox systems. Healthy and inflamed periodontal tissues were collected to evaluate NOX4 and redox systems by immunohistochemistry. We found significantly increased NOX4 levels after hypoxic or inflammatory stimulation in PDL cells (P < 0.001) which was even more pronounced after combination of the stimuli. This was accompanied by a significant upregulation of ROS and catalase (P < 0.001). However, prolonged incubation with both stimuli induced a reduction of catalase indicating a collapse of the protective machinery favoring ROS increase and the progression of inflammatory oral diseases. Analysis of inflamed tissues confirmed our hypothesis. In conclusion, we demonstrated that the interplay of NOX4 and redox systems is crucial for ROS formation which plays a pivotal role during oral diseases. PMID:25374447

  4. Heat shock increases oxidative stress to modulate growth and physico-chemical attributes in diverse maize cultivars

    NASA Astrophysics Data System (ADS)

    Hussain, Iqbal; Ashraf, Muhammad Arslan; Rasheed, Rizwan; Iqbal, Muhammad; Ibrahim, Muhammad; Ashraf, Shamila

    2016-10-01

    The present investigation was conducted to appraise the physiochemical adjustments in contrasting maize cultivars, namely, PakAfgoi (tolerant) and EV-5098 (sensitive) subjected to heat shock. Seven-day-old seedlings were exposed to heat shock for different time intervals (1, 3, 6, 24, 48 and 72 h) and data for various physiochemical attributes determined to appraise time course changes in maize. After 72 h of heat shock, the plants were grown under normal conditions for 5 d and data for different growth attributes and photosynthetic pigments recorded. Exposure to heat shock reduced growth and photosynthetic pigments in maize cultivars. The plants exposed to heat shock for up to 3 h recovered growth and photosynthetic pigments when stress was relieved. A time course rise in the relative membrane permeability, hydrogen peroxide (H2O2) and malondialdehyde contents was recorded particularly in the EV-5098 indicating that heat shock-induced oxidative stress. Activities of different enzymatic antioxidants greatly altered due to heat shock. For instance, an increase in superoxide dismutase activity was recorded in both maize cultivars. The activity of ascorbate peroxidase was greater in Pak-Afgoi. However, the peroxidase and catalase activities were higher in plants of EV-5098. Heat shock caused a significant rise in the proline and decline in the total free amino acids. Overall, the performance of Pak-Afgoi was better in terms of having lesser oxidative damage and greater cellular levels of proline. The results suggested that oxidative stress indicators (relative membrane permeability, H2O2 and malondialdehyde) and proline can be used as markers for heat shock tolerant plants.

  5. The acute antinociceptive effect of hyperbaric oxygen is not accompanied by an increase in markers of oxidative stress

    PubMed Central

    Liu, Shulin; Shirachi, Donald Y.; Quock, Raymond M.

    2014-01-01

    Aims Exposure to hyperbaric oxygen (HBO2) causes an antinociceptive response in mice. However, breathing oxygen (O2) at an elevated pressure can potentially cause oxygen toxicity. The aim of this study was to identify the determinants of HBO2 antinociception and the toxicity profile of HBO2. Main methods Male NIH Swiss mice were assessed for acute antinociceptive responsiveness under room air or 100% O2 at 1.0 or 3.5 atmospheres absolute (ATA), using the acetic acid-induced abdominal constriction test. For the oxygen toxicity test, mice were exposed to 3.5 ATA oxygen for 11 min, 60 min, 60 min daily for 2 days (120 min) or 60 min daily for 4 days (240 min), then assessed by analyzing the levels of two oxidative stress markers, MDA (malondialdehyde) and protein carbonyl in brain, spinal cord and lung. Key Findings Only the combination of 100% O2 and 3.5 ATA caused significant antinociception. The antinociceptive effect of 100% O2 was pressure-dependent up to 3.5 ATA. In the oxygen toxicity test, mice exposed to HBO2 for different time intervals had levels of brain, spinal cord and lung MDA and protein carbonyl that were comparable to that of control animals exposed to room air. Significance Treatment with 100% O2 evokes a pressure-dependent antinociceptive effect. Since there was no significant increase in levels of the oxidative stress markers in the tested tissues, it is concluded HBO2 at 3.5 ATA produces antinociception in the absence of oxidative stress in mice. PMID:24418003

  6. Low Cobalamin Levels as Predictors of Cobalamin Deficiency: Importance of Comorbidities Associated with Increased Oxidative Stress.

    PubMed

    Solomon, Lawrence R

    2016-01-01

    Cobalamin (B12) deficiency can lead to irreversible neurocognitive changes if unrecognized. Screening involves measurement of serum cobalamin levels, but the sensitive metabolic indicators of cobalamin deficiency, methylmalonic acid (MMA) and homocysteine (HCys), may be normal when cobalamin values are low and elevated when cobalamin values are normal. Because cobalamin is inactivated by oxidation, the relationship between these metabolites and comorbidities associated with increased oxidative stress (oxidant risks) in subjects with low and low-normal cobalamin levels was studied. A retrospective record-review was conducted of community-dwelling adults evaluated for cobalamin deficiency during a 12-year period with serum cobalamin values in the low (≤ 200 pg/mL; n = 49) or low-normal (201-300 pg/mL; n = 187) range and concurrent measurement of MMA. When "No" oxidant risk was present, elevated MMA (>250 nmol/L) and HCys (>12.1 μmol/L) values occurred in 50% and 30% of subjects, respectively (P <.01). In contrast, when "Three or More" oxidant risks were present, mean MMA and HCys values were significantly higher, and elevated MMA and HCys values occurred in 84% and 78% of these subjects, respectively (P ≤.012). Pharmacologic doses of cyanocobalamin significantly decreased metabolite values in ≥ 94% of treated subjects. In subjects with low or low-normal cobalamin values, metabolic evidence of cobalamin deficiency is more frequent when 3 or more oxidant risks are present. Thus, defining a low serum cobalamin level to screen for cobalamin deficiency may be a "moving target" due to the variable presence and severity of often subtle, confounding clinical conditions in individual subjects. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Estrogens increase cystathionine-γ-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats.

    PubMed

    Zhu, Xiaoyan; Tang, Zhiping; Cong, Binhai; Du, Jiankui; Wang, Changnan; Wang, Long; Ni, Xin; Lu, Jianqiang

    2013-10-01

    Hydrogen sulfide (H2S), generated in the myocardium predominantly via cystathionine-γ-lyase (CSE), is cardioprotective. The objectives of the present study were to investigate the effects of estrogens on CSE expression and H2S generation in the myocardium and to examine whether serum 17β-estradiol (E2) level is associated with CSE activity and H2S generation and whether H2S or E2 level is associated with proinflammatory cytokines and oxidative stress status. Ovariectomized Sprague-Dawley rats received subcutaneous E2 (30 μg/kg/d) or vehicle for 12 weeks. At the end of the 12-week treatment, CSE expression, H2S generation, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, interleukin (IL)-6 concentration, and tumor necrosis factor-α (TNF-α) concentration in the left ventricle were determined. E2 increased CSE expression and H2S generation in the myocardium of ovariectomized rats. H2S production rate and serum E2 were positively correlated. E2 increased GSH/GSSG ratio, T-AOC, CAT, and SOD activity but decreased IL-6 and TNF-α levels. Serum E2 level was positively correlated with GSH/GSSG ratio, T-AOC, CAT, and SOD activity, and inversely correlated with IL-6 and TNF-α levels. H2S generation rate was positively correlated with T-AOC and GSH/GSSG ratio, and inversely correlated with IL-6 and TNF-α levels. E2 increases CSE expression and endogenous H2S generation in the myocardium. The effects of E2 are associated with decreased oxidative stress and inflammatory status. Our data suggest that estrogens might exert cardioprotective effects through up-regulation of CSE expression and H2S generation.

  8. Oxidative stress and antioxidant responses to increasing concentrations of trivalent chromium in the Andean crop species Chenopodium quinoa Willd.

    PubMed

    Scoccianti, Valeria; Bucchini, Anahi E; Iacobucci, Marta; Ruiz, Karina B; Biondi, Stefania

    2016-11-01

    Quinoa (Chenopodium quinoa Willd), an ancient Andean seed crop, exhibits exceptional nutritional properties and resistance to abiotic stress. The species' tolerance to heavy metals has, however, not yet been investigated nor its ability to take up and translocate chromium (Cr). This study aimed to investigate the metabolic adjustments occurring upon exposure of quinoa to several concentrations (0.01-5mM) of CrCl3. Young hydroponically grown plants were used to evaluate Cr uptake, growth, oxidative stress, and other biochemical parameters three and/or seven days after treatment. Leaves accumulated the lowest amounts of Cr, while roots and stems accumulated the most at low and at high metal concentrations, respectively. Fresh weight and photosynthetic pigments were reduced only by the higher Cr(III) doses. Substantially increased lipid peroxidation, hydrogen peroxide, and proline levels were observed only with 5mM Cr(III). Except for a significant decrease at day 7 with 5mM Cr(III), total polyphenols and flavonoids maintained control levels in Cr(III)-treated plants, whereas antioxidant activity increased in a dose-dependent manner. Maximum polyamine accumulation was observed in 1mM CrCl3-treated plants. Even though α- and γ-tocopherols also showed enhanced levels only with the 1mM concentration, tyrosine aminotransferase (TAT, EC 2.6.1.5) activity increased under Cr(III) treatment in a dose- and time-dependent manner. Taken together, results suggest that polyamines, tocopherols, and TAT activity could contribute to tolerance to 1mM Cr(III), but not to the highest concentration that, instead, generated oxidative stress.

  9. Passive smoking reduces and vitamin C increases exercise-induced oxidative stress: does this make passive smoking an anti-oxidant and vitamin C a pro-oxidant stimulus?

    PubMed

    Theodorou, Anastasios A; Paschalis, Vassilis; Kyparos, Antonios; Panayiotou, George; Nikolaidis, Michalis G

    2014-11-07

    The current interpretative framework states that, for a certain experimental treatment (usually a chemical substance) to be classified as "anti-oxidant", it must possess the property of reducing (or even nullifying) exercise-induced oxidative stress. The aim of the study was to compare side by side, in the same experimental setup, redox biomarkers responses to an identical acute eccentric exercise session, before and after chronic passive smoking (considered a pro-oxidant stimulus) or vitamin C supplementation (considered an anti-oxidant stimulus). Twenty men were randomly assigned into either passive smoking or vitamin C group. All participants performed two acute eccentric exercise sessions, one before and one after either exposure to passive smoking or vitamin C supplementation for 12 days. Vitamin C, oxidant biomarkers (F2-isoprostanes and protein carbonyls) and the non-enzymatic antioxidant (glutathione) were measured, before and after passive smoking, vitamin C supplementation or exercise. It was found that chronic exposure to passive smoking increased the level of F2-isoprostanes and decreased the level of glutathione at rest, resulting in minimal increase or absence of oxidative stress after exercise. Conversely, chronic supplementation with vitamin C decreased the level of F2-isoprostanes and increased the level of glutathione at rest, resulting in marked exercise-induced oxidative stress. Contrary to the current scientific consensus, our results show that, when a pro-oxidant stimulus is chronically delivered, it is more likely that oxidative stress induced by subsequent exercise is decreased and not increased. Reversely, it is more likely to find greater exercise-induced oxidative stress after previous exposure to an anti-oxidant stimulus. We believe that the proposed framework will be a useful tool to reach more pragmatic explanations of redox biology phenomena. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Oxidative stress in myopia.

    PubMed

    Francisco, Bosch-Morell; Salvador, Mérida; Amparo, Navea

    2015-01-01

    Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem.

  11. Oxidative Stress in Myopia

    PubMed Central

    Francisco, Bosch-Morell; Salvador, Mérida; Amparo, Navea

    2015-01-01

    Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem. PMID:25922643

  12. Strawberry or blueberry supplementation may protect against increased oxidative stress vulnerability from both irradiation and aging

    NASA Astrophysics Data System (ADS)

    Joseph, J. A.; Shukitt-Hale, B.; Carey, A.; Rabin, B. M.

    In several studies we have now shown that there are some interesting parallels between aging and the effects of heavy particle irradiation (56Fe) in a rat model. Interestingly this research also has shown that, much as has been seen in aged animals, dietary supplementation with high antioxidant-strawberry (SB) or blueberry (BB) extracts (2% of the diet) reversed many of the age-related changes. Similarly, supplementing the diets of young rats with SBs or BBs (2% of diet as in the aged animals) for 8 weeks prior to being exposed to 56Fe (1 GeV/n), using the AGS or NSRL at Brookhaven National Laboratory, prevented the deleterious effects of the radiation exposure on the motor, cognitive and neuronal parameters described above. In the present experiment we examined whether striatal tissue obtained from BB- or SB-supplemented or control-fed, irradiated or non-radiated, young rats would show differential sensitivity (as assessed via decrements in mAChR stimulation of dopamine release) to hydrogen peroxide, a reactive oxygen species (ROS) generating agent. The results indicated that, just as we had seen previously with respect to radiation protection in the parameters described above, the tissue from the SB or BB-supplemented irradiated or non-radiated animals showed increased mAChR-stimulated DA release from the striatal tissue following hydrogen peroxide exposure compared to that seen in non-supplemented irradiated or non-radiated animals (e.g., DA rels. p moles/mg protein, rad + H202 non-supplemented = 90, SB = 260, BB = 360). These results show that aging and irradiation may produce similar decrements in dopamine release and that, much as we have seen previously with age, radiation enhances the vulnerability to oxidative stressors, but these are reduced with SB or BB supplementation. They are discussed in-terms of protection against the effects of exposure to heavy particles and aging via nutritional supplementation with foods that are high in antioxidant activity

  13. Oxidative stress and ageing.

    PubMed

    Birch-Machin, M A; Bowman, A

    2016-10-01

    Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering

  14. High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects.

    PubMed

    Yu, Jingwen; Wu, Yanqing; Yang, Peixin

    2016-05-01

    Aberrant epigenetic modifications are implicated in maternal diabetes-induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress-resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1-7), pre-gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down-regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over-expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures. 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a superoxide generating agent, mimicked high glucose-suppressed SIRT2 and SIRT6 expression. The acetylation of histone 3 at lysine residues 56 (H3K56), H3K14, H3K9, and H3K27, putative substrates of SIRT2 and SIRT6, was increased by maternal diabetes in vivo or high glucose in vitro, and these increases were blocked by SOD1 over-expression or tempol treatment. SIRT2 or SIRT6 over-expression abrogated high glucose-suppressed SIRT2 or SIRT6 expression, and prevented the increase in acetylation of their histone substrates. The potent sirtuin activator (SRT1720) blocked high glucose-increased histone acetylation and NTD formation, whereas the combination of a pharmacological SIRT2 inhibitor and a pan SIRT inhibitor mimicked the effect of high glucose on increased histone acetylation and NTD induction. Thus, diabetes in vivo or high glucose in vitro suppresses SIRT2 and SIRT6 expression through oxidative stress, and sirtuin down-regulation-induced histone acetylation may be involved in diabetes-induced NTDs. The mechanism underlying pre-gestational diabetes-induced neural tube defects (NTDs) is still elusive. Our study unravels a new epigenetic mechanism in which maternal diabetes-induced oxidative stress represses

  15. Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress.

    PubMed

    Mimura, Kousaku; Kua, Ley-Fang; Shimasaki, Noriko; Shiraishi, Kensuke; Nakajima, Shotaro; Siang, Lim Kee; Shabbir, Asim; So, Jimmy; Yong, Wei-Peng; Kono, Koji

    2017-02-21

    Adoptive transfer of immune cells, such as T lymphocytes and NK cells, has potential to control cancer growth. However, this can be counteracted by immune escape mechanisms within the tumor microenvironment, including those mediated by reactive oxygen species (ROS). Here, we determined the levels of anti-oxidant molecules in NK cells and their capacity to overcome ROS-induced immune suppression. We investigated the effect of H2O2 on resting NK cells, IL-2-activated NK cells and NK cells expanded by coculture with the K562 leukemia cell line genetically modified to express membrane-bound IL-15 and 4-1BB ligand (K562-mb15-41BBL). Expression of anti-oxidant and anti-apoptotic genes was evaluated by expression array, and protein levels of anti-oxidant molecules by Western blot. Activated NK cells, IL-2-activated NK cells and NK cells expanded by K562-mb15-41BBL were significantly more resistant to H2O2-induced cell death than resting NK. Thioredoxin-1 (TXN1) and peroxiredoxin-1 (PRDX1) were also up-regulated in activated NK cells. Moreover, H2O2-induced cell death after IL-2 activation was significantly induced in the presence of an anti-TXN1-neutralising antibody. Collectively, these data document that activated NK cells can resist to H2O2-induced cell death by up-regulation of TXN1.

  16. N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content

    SciTech Connect

    Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee; Does, Mark D.; Valentine, Holly L.; Valentine, William M.

    2009-08-15

    dithiocarbamate-mediated inhibition of proteasome function and inhibition of cuproenzyme activity to neurotoxicity, and also to assess the potential of dithiocarbamates to promote oxidative stress and injury within the central nervous system. These evaluations were performed using an established model for dithiocarbamate-mediated demyelination in the rat utilizing sciatic nerve, spinal cord and brain samples obtained from rats exposed to N,N-diethyldithiocarbamate (DEDC) by intra-abdominal pumps for periods of 2, 4, and 8 weeks and from non exposed controls. The data supported the ability of DEDC to increase copper within myelin and to enhance oxidative stress prior to structural changes detectable by MET{sub 2}. Evidence was also obtained that the excess copper produced by DEDC in the central nervous system is redox active and promotes oxidative injury.

  17. N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content.

    PubMed

    Viquez, Olga M; Lai, Barry; Ahn, Jae Hee; Does, Mark D; Valentine, Holly L; Valentine, William M

    2009-08-15

    -mediated inhibition of proteasome function and inhibition of cuproenzyme activity to neurotoxicity, and also to assess the potential of dithiocarbamates to promote oxidative stress and injury within the central nervous system. These evaluations were performed using an established model for dithiocarbamate-mediated demyelination in the rat utilizing sciatic nerve, spinal cord and brain samples obtained from rats exposed to N,N-diethyldithiocarbamate (DEDC) by intra-abdominal pumps for periods of 2, 4, and 8 weeks and from non exposed controls. The data supported the ability of DEDC to increase copper within myelin and to enhance oxidative stress prior to structural changes detectable by MET(2). Evidence was also obtained that the excess copper produced by DEDC in the central nervous system is redox active and promotes oxidative injury.

  18. A Chilean Berry Concentrate Protects against Postprandial Oxidative Stress and Increases Plasma Antioxidant Activity in Healthy Humans

    PubMed Central

    Ávila, Felipe; Echeverria, Guadalupe; Perez, Druso; Trejo, Sebastian; Leighton, Federico

    2017-01-01

    This study formulated and characterized an antioxidant-rich concentrate of berries (BPC-350) produced in Chile, which was used to perform a crossover study aimed at determining the effect of the berries on the modulation of plasma postprandial oxidative stress and antioxidant status. Healthy male volunteers (N = 11) were randomly assigned to three experimental meals: (1) 250 g of ground turkey burger (GTB) + 500 mL of water; (2) 250 g of GTB + 500 mL of 5% BPC-350; (3) 250 g of GTB prepared with 6% BPC-350 + 500 mL of 5% BPC-350. Venous blood samples were collected prior to meal intake and every hour for six hours after intake. Malondialdehyde (MDA), carbonyls in proteins, and DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant capacity were quantified in plasma. Significant differences indicated that BPC-350 decreases MDA plasma concentration and protein carbonyls (p < 0.05). Additionally, a significant increase in the DPPH antioxidant capacity was observed in Meals 2 and 3 when compared to Meal 1 (p < 0.05). The results are discussed in terms of oxidative reactions that occur during digestion at the stomach level and the important effect of oxidative reactions that occur during the thermal processing of red meat. PMID:28243359

  19. A Chilean Berry Concentrate Protects against Postprandial Oxidative Stress and Increases Plasma Antioxidant Activity in Healthy Humans.

    PubMed

    Urquiaga, Ines; Ávila, Felipe; Echeverria, Guadalupe; Perez, Druso; Trejo, Sebastian; Leighton, Federico

    2017-01-01

    This study formulated and characterized an antioxidant-rich concentrate of berries (BPC-350) produced in Chile, which was used to perform a crossover study aimed at determining the effect of the berries on the modulation of plasma postprandial oxidative stress and antioxidant status. Healthy male volunteers (N = 11) were randomly assigned to three experimental meals: (1) 250 g of ground turkey burger (GTB) + 500 mL of water; (2) 250 g of GTB + 500 mL of 5% BPC-350; (3) 250 g of GTB prepared with 6% BPC-350 + 500 mL of 5% BPC-350. Venous blood samples were collected prior to meal intake and every hour for six hours after intake. Malondialdehyde (MDA), carbonyls in proteins, and DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant capacity were quantified in plasma. Significant differences indicated that BPC-350 decreases MDA plasma concentration and protein carbonyls (p < 0.05). Additionally, a significant increase in the DPPH antioxidant capacity was observed in Meals 2 and 3 when compared to Meal 1 (p < 0.05). The results are discussed in terms of oxidative reactions that occur during digestion at the stomach level and the important effect of oxidative reactions that occur during the thermal processing of red meat.

  20. Soy Isoflavone Protects Myocardial Ischemia/Reperfusion Injury through Increasing Endothelial Nitric Oxide Synthase and Decreasing Oxidative Stress in Ovariectomized Rats

    PubMed Central

    Tang, Yan; Li, Shuangyue; Zhang, Ping; Zhu, Jinbiao; Meng, Guoliang; Xie, Liping; Yu, Ying; Ji, Yong; Han, Yi

    2016-01-01

    There is a special role for estrogens in preventing and curing cardiovascular disease in women. Soy isoflavone (SI), a soy-derived phytoestrogen, has similar chemical structure to endogenous estrogen-estradiol. We investigate to elucidate the protective mechanism of SI on myocardial ischemia/reperfusion (MI/R) injury. Female SD rats underwent bilateral ovariectomy. One week later, rats were randomly divided into several groups, sham ovariectomy (control group), ovariectomy with MI/R, or ovariectomy with sham MI/R. Other ovariectomy rats were given different doses of SI or 17β-estradiol (E2). Four weeks later, they were exposed to 30 minutes of left coronary artery occlusion followed by 6 or 24 hours of reperfusion. SI administration significantly reduced myocardial infarct size and improved left ventricle function and restored endothelium-dependent relaxation function of thoracic aortas after MI/R in ovariectomized rats. SI also decreased serum creatine kinase and lactate dehydrogenase activity, reduced plasma malonaldehyde, and attenuated oxidative stress in the myocardium. Meanwhile, SI increased phosphatidylinositol 3 kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) signal pathway. SI failed to decrease infarct size of hearts with I/R in ovariectomized rats if PI3K was inhibited. Overall, these results indicated that SI protects myocardial ischemia/reperfusion injury in ovariectomized rats through increasing PI3K/Akt/eNOS signal pathway and decreasing oxidative stress. PMID:27057277

  1. Increase in antioxidant-defense gene transcripts, stress tolerance and biocontrol efficacy of Candida oleophila following sublethal oxidative stress exposure

    USDA-ARS?s Scientific Manuscript database

    Candida oleophila is one of several yeast species that have been used as bicontrol agents to manage postharvest diseases of fruits and vegetables. Current research is aimed at improving the tolerance of various antagonistic yeasts to environmental stresses in order to improve their efficacy. We ex...

  2. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress

    PubMed Central

    Santos-Parker, Jessica R.; Strahler, Talia R.; Bassett, Candace J.; Bispham, Nina Z.; Chonchol, Michel B.; Seals, Douglas R.

    2017-01-01

    We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida®; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBFACh; resistance artery endothelial function) increased 37% following curcumin supplementation (107±13 vs. 84±11 AUC at baseline, P=0.03), but not placebo (P=0.2). Curcumin treatment augmented the acute reduction in FBFACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA; P=0.03), and reduced the acute increase in FBFACh to the antioxidant vitamin C (P=0.02), whereas placebo had no effect (both P>0.6). Similarly, brachial artery flow-mediated dilation (conduit artery endothelial function) increased 36% in the curcumin group (5.7±0.4 vs. 4.4±0.4% at baseline, P=0.001), with no change in placebo (P=0.1). Neither curcumin nor placebo influenced large elastic artery stiffness (aortic pulse wave velocity or carotid artery compliance) or circulating biomarkers of oxidative stress and inflammation (all P>0.1). In healthy middle-aged and older adults, 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress, while also improving conduit artery endothelial function. PMID:28070018

  3. Increased dietary protein elevates plasma uric acid and is associated with decreased oxidative stress in rapidly-growing broilers.

    PubMed

    Machín, M; Simoyi, M F; Blemings, K P; Klandorf, H

    2004-03-01

    Uric acid is an important antioxidant and methods to elevate its plasma concentration may be important in animal health. In a first study, the effect of dietary protein on plasma uric acid (PUA) and glucose concentrations were determined in 3-week-old chicks. Twenty-four broiler chicks were randomly assigned to four diets: a commercial control diet (C, 20% crude protein), low protein (LP) containing 10% casein, medium protein (MP) containing 20% casein or high protein (HP) containing 45% casein for a 3-week experiment. PUA concentration increased (P<0.05) in chicks fed HP diet and declined (P<0.05) in chicks fed LP while plasma glucose concentrations were lower (P<0.05) in chicks fed the LP diet at the end of the study. In a second study, PUA and leukocyte oxidative activity (LOA) were determined in broilers fed C, LP, MP or HP diets for 4 weeks. As in the first study, dietary protein directly affected PUA concentrations. In birds consuming HP diets, PUA was negatively correlated (P=0.06) with lowered LOA. These data support the view that increases in dietary protein can increase PUA concentrations, which can ameliorate oxidative stress.

  4. Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers

    DTIC Science & Technology

    2012-02-01

    to HBMEC showed increase in ROS levels as compared to control, and this increased in ROS formation was abrogated by the antioxidant uric acid , UA...in HBMEC permeability was observed by ROS and these changes were inhibited in the presence of UA antioxidant, uric acid , indicating the involvement

  5. Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress.

    PubMed

    Patki, Gaurav; Solanki, Naimesh; Atrooz, Fatin; Allam, Farida; Salim, Samina

    2013-11-20

    In the present study, we have examined the behavioral and biochemical effect of induction of psychological stress using a modified version of the resident-intruder model for social stress (social defeat). At the end of the social defeat protocol, body weights, food and water intake were recorded, depression and anxiety-like behaviors as well as memory function was examined. Biochemical analysis including oxidative stress measurement, inflammatory markers and other molecular parameters, critical to behavioral effects were examined. We observed a significant decrease in the body weight in the socially defeated rats as compared to the controls. Furthermore, social defeat increased anxiety-like behavior and caused memory impairment in rats (P<0.05). Socially defeated rats made significantly more errors in long term memory tests (P<0.05) as compared to control rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK1/2), and an inflammatory marker, interleukin (IL)-6 were activated (P<0.05), while the protein levels of glyoxalase (GLO)-1, glutathione reductase (GSR)-1, calcium/calmodulin-dependent protein kinase type (CAMK)-IV, cAMP-response-element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were significantly less (P<0.05) in the hippocampus, but not in the prefrontal cortex and amygdala of socially defeated rats, when compared to control rats. We suggest that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF levels in specific brain areas, leading to oxidative stress-induced anxiety-depression-like behaviors and as well as memory impairment in rats.

  6. D-004 ameliorates phenylephrine-induced urodynamic changes and increased prostate and bladder oxidative stress in rats

    PubMed Central

    Oyarzábal, Ambar; Pérez, Yohani; Mas, Rosa; Ravelo, Yazmin; Jiménez, Sonia

    2015-01-01

    Background Lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) mainly depend on alpha1-adrenoreceptors (α1-ADR) stimulation, but a link with oxidative stress (OS) is also involved. D-004, a lipid extract of Roystonea regia fruits, antagonizes ADR-induced responses and produces antioxidant effects. The objective of this study was to investigate whether D-004 produce antioxidant effects in rats with phenylephrine (PHE)-induced urodynamic changes. Methods Rats were randomized into eight groups (ten rats/group): a negative vehicle control and seven groups injected with PHE: a positive control, three treated with D-004 (200, 400 and 800 mg/kg) and three others with tamsulosin (0.4 mg/kg), grape seed extract (GSE) (250 mg/kg) and vitamin E (VE) (250 mg/kg), respectively. Results Effects on urinary total volume (UTV), volume voided per micturition (VM), malondialdehyde (MDA) and carbonyl groups (CG) concentrations in prostate and bladder homogenates were study outcomes. While VM and UTV lowered significantly in the positive control as compared to the negative control group, the opposite occurred with prostate and bladder MDA and CG values. D-004 (200-800 mg/kg) increased significantly both VM and UTV, lowered significantly MDA in prostate and bladder homogenates, and reduced GC levels only in the prostate. Tamsulosin increased significantly VM and UTV, but unchanged oxidative variables. GSE and VE unchanged the UTV, whereas VE, not GSE, modestly but significantly attenuated the PHE-induced decrease of VM. Conclusions Single oral administration of D-004 (200-800 mg/kg) was the only treatment that ameliorated the urodynamic changes and reduced increased oxidative variables in the prostate of rats with PHE-induced prostate hyperplasia. PMID:26816837

  7. Yeast NDI1 Improve Oxidative Phosphorylation Capacity and Increases Protection Against Oxidative Stress and Cell Death in Cells Carrying a Leber’s Hereditary Optic Neuropathy Mutation

    PubMed Central

    Park, Jeong Soon; Li, You-fen; Bai, Yidong

    2007-01-01

    G11778A in the subunit ND4 gene of NADH dehydrogenase complex is the most common primary mutation found in Leber’s hereditary optic neuropathy (LHON) patients. The NDI1 gene, which encodes the internal NADH -quinone oxidoreductase in Saccharomyces cerevisiae, was introduced into the nuclear genome of a mitochondrial defective human cell line, Le1.3.1, carrying the G11778A mutation. In transformant cell lines, LeNDI1-1 and -2, total and complex I-dependent respiration were fully restored and largely resistant to complex I inhibitor, rotenone, indicating a dominant role of NDI1 in the transfer of electrons in the host cells. Whereas the original mutant Le1.3.1 cell grows poorly in medium containing galactose, the transformants have a fully restored growth capacity in galactose medium, although the ATP production was not totally recovered. Furthermore, the increased oxidative stress in the cells carrying the G11778A mutation was alleviated in transformants, demonstrated by a decreased reactive oxygen species (ROS) level. Finally, transformants were also shown to be desensitized to induction to apoptosis and also exhibit greater resistance to paraquat-induced cell death. It is concluded that the yeast ND11 enzyme can improve the oxidative phosphorylation capacity in cells carrying the G11778A mutation and protect the cells from oxidative stress and cell death. PMID:17320357

  8. Yeast NDI1 improves oxidative phosphorylation capacity and increases protection against oxidative stress and cell death in cells carrying a Leber's hereditary optic neuropathy mutation.

    PubMed

    Park, Jeong Soon; Li, You-Fen; Bai, Yidong

    2007-05-01

    G11778A in the subunit ND4 gene of NADH dehydrogenase complex is the most common primary mutation found in Leber's hereditary optic neuropathy (LHON) patients. The NDI1 gene, which encodes the internal NADH-quinone oxidoreductase in Saccharomyces cerevisiae, was introduced into the nuclear genome of a mitochondrial defective human cell line, Le1.3.1, carrying the G11778A mutation. In transformant cell lines, LeNDI1-1 and -2, total and complex I-dependent respiration were fully restored and largely resistant to complex I inhibitor, rotenone, indicating a dominant role of NDI1 in the transfer of electrons in the host cells. Whereas the original mutant Le1.3.1 cell grows poorly in medium containing galactose, the transformants have a fully restored growth capacity in galactose medium, although the ATP production was not totally recovered. Furthermore, the increased oxidative stress in the cells carrying the G11778A mutation was alleviated in transformants, demonstrated by a decreased reactive oxygen species (ROS) level. Finally, transformants were also shown to be desensitized to induction to apoptosis and also exhibit greater resistance to paraquat-induced cell death. It is concluded that the yeast NDI1 enzyme can improve the oxidative phosphorylation capacity in cells carrying the G11778A mutation and protect the cells from oxidative stress and cell death.

  9. Systemic alterations in the metabolome of diabetic NOD mice delineate increased oxidative stress accompanied by reduced inflammation and hypertriglyceremia.

    PubMed

    Fahrmann, Johannes; Grapov, Dmitry; Yang, Jun; Hammock, Bruce; Fiehn, Oliver; Bell, Graeme I; Hara, Manami

    2015-06-01

    Nonobese diabetic (NOD) mice are a commonly used model of type 1 diabetes (T1D). However, not all animals will develop overt diabetes despite undergoing similar autoimmune insult. In this study, a comprehensive metabolomic approach, consisting of gas chromatography time-of-flight (GC-TOF) mass spectrometry (MS), ultra-high-performance liquid chromatography-accurate mass quadruple time-of-flight (UHPLC-qTOF) MS and targeted UHPLC-tandem mass spectrometry-based methodologies, was used to capture metabolic alterations in the metabolome and lipidome of plasma from NOD mice progressing or not progressing to T1D. Using this multi-platform approach, we identified >1,000 circulating lipids and metabolites in male and female progressor and nonprogressor animals (n = 71). Statistical and multivariate analyses were used to identify age- and sex-independent metabolic markers, which best differentiated metabolic profiles of progressors and nonprogressors. Key T1D-associated perturbations were related with 1) increases in oxidation products glucono-δ-lactone and galactonic acid and reductions in cysteine, methionine and threonic acid, suggesting increased oxidative stress; 2) reductions in circulating polyunsaturated fatty acids and lipid signaling mediators, most notably arachidonic acid (AA) and AA-derived eicosanoids, implying impaired states of systemic inflammation; 3) elevations in circulating triacylglyercides reflective of hypertriglyceridemia; and 4) reductions in major structural lipids, most notably lysophosphatidylcholines and phosphatidylcholines. Taken together, our results highlight the systemic perturbations that accompany a loss of glycemic control and development of overt T1D.

  10. Six weeks of aerobic dance exercise improves blood oxidative stress status and increases interleukin-2 in previously sedentary women.

    PubMed

    Leelarungrayub, Donrawee; Saidee, Kunteera; Pothongsunun, Prapas; Pratanaphon, Sainetee; YanKai, Araya; Bloomer, Richard J

    2011-07-01

    This study evaluated the change in blood oxidative stress, blood interleukin-2, and physical performance following 6 weeks of moderate intensity and duration aerobic dance exercise in 24 sedentary women. Blood samples were collected at rest twice before (baseline) and after the 6-week intervention for analysis of protein hydroperoxide (PrOOH), malondialdehyde (MDA), total anti-oxidant capacity (TAC), and interleukin-2 (IL-2) levels. Maximal treadmill run time (Time(max)) and maximal oxygen consumption (VO(2max)) were also measured. All variables were statistically analyzed with a repeated measurement ANOVA and Tukey post hoc. No differences were noted in any variable during the baseline period (p > 0.05). After aerobic dance exercise, VO(2max), Time(max), TAC and IL-2 were significantly increased, whereas MDA levels were decreased significantly (p < 0.05). PrOOH did not change either between baseline measures or after exercise. It can be concluded that aerobic dance exercise at a moderate intensity and duration can improve physical fitness, decrease MDA, and increase TAC and IL-2 in previously sedentary women.

  11. Blackcurrant seed press residue increases tocopherol concentrations in serum and stool whilst biomarkers in stool and urine indicate increased oxidative stress in human subjects.

    PubMed

    Helbig, Dorit; Wagner, Andreas; Glei, Michael; Basu, Samar; Schubert, Rainer; Jahreis, Gerhard

    2009-08-01

    Berry seeds are a tocopherol-rich by-product of fruit processing without specific commercial value. In a human intervention study, the physiological impact of blackcurrant seed press residue (PR) was tested. Thirty-six women (aged 24 +/- 3 years; twenty non-smokers, sixteen smokers) consumed 250 g bread/d containing 8% PR for a period of 4 weeks (period 3). Comparatively, a control bread without PR (250 g/d) was tested (period 2) and baseline data were obtained (period 1). Blood, stool and 24 h urine were collected during a 5 d standardised diet within each period. Tocopherol and Fe intakes were calculated from food intake. In serum, tocopherol concentration and Fe parameters were determined. In urine, oxidative stress markers 8-oxo-2'-deoxyguanosine, 8-iso-PGF2alpha and inflammatory response marker 15-keto-dihydro-PGF2alpha were analysed. Stool tocopherol concentration, genotoxicity of faecal water (comet assay) and antioxidant capacity of stool (aromatic hydroxylation of salicylic acid) were determined. Fe and total tocopherol intake, total tocopherol concentrations in serum and stool, and genotoxicity of faecal water increased with PR bread consumption (P < 0.05). The antioxidant capacity of stool decreased between baseline and intervention, expressed by increased formation of 2,3- and 2,5-dihydroxybenzoic acid in vitro (P < 0.05). In smokers, 8-oxo-2'-deoxyguanosine increased with PR consumption (P < 0.05). Prostane concentrations were unaffected by PR bread consumption. In summary, the intake of bread containing blackcurrant PR for 4 weeks increased serum and stool total tocopherol concentrations. However, various biomarkers indicated increased oxidative stress, suggesting that consumption of ground berry seed may not be of advantage.

  12. Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf.

    PubMed

    Ogawa, Takahiro; Kodera, Yukihiro; Hirata, Dai; Blackwell, T Keith; Mizunuma, Masaki

    2016-02-22

    Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging.

  13. The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells.

    PubMed

    Arany, Istvan; Hall, Samuel; Reed, Dustin K; Dixit, Mehul

    2016-09-01

    Nicotine (NIC) exposure augments free fatty acid (FFA) deposition and oxidative stress, with a concomitant increase in the expression of the pro-oxidant p66shc. In addition, a decrease in the antioxidant manganese superoxide dismutase (MnSOD) has been observed in the kidneys of mice fed a high‑fat diet. The present study aimed to determine whether the pro‑oxidant p66shc mediates NIC‑dependent increases in renal oxidative stress by augmenting the production of reactive oxygen species (ROS) and suppressing the FFA‑induced antioxidant response in cultured NRK52E renal proximal tubule cells. Briefly, NRK52E renal proximal tubule cells were treated with 200 µM NIC, 100 µM oleic acid (OA), or a combination of NIC and OA. The expression levels of p66shc and MnSOD were modulated according to genetic methods. ROS production and cell injury, in the form of lactate dehydrogenase release, were subsequently detected. Promoter activity of p66shc and MnSOD, as well as forkhead box (FOXO)‑dependent transcription, was investigated using reporter luciferase assays. The results demonstrated that NIC exacerbated OA‑mediated intracellular ROS production and cell injury through the transcriptional activation of p66shc. NIC also suppressed OA‑mediated induction of the antioxidant MnSOD promoter activity through p66shc‑dependent inactivation of FOXO activity. Overexpression of p66shc and knockdown of MnSOD had the same effect as treatment with NIC on OA‑mediated lipotoxicity. These data may be used to generate a therapeutic means to ameliorate renal lipotoxicity in obese smokers.

  14. Infiltrating T lymphocytes in the kidney increase oxidative stress and participate in the development of hypertension and renal disease.

    PubMed

    De Miguel, Carmen; Guo, Chuanling; Lund, Hayley; Feng, Di; Mattson, David L

    2011-03-01

    The present studies examined the role and mechanism of action of infiltrating T lymphocytes in the kidney during salt-sensitive hypertension. Infiltrating T lymphocytes in the Dahl salt-sensitive (SS) kidney significantly increased from 7.2 ± 1.8 × 10(5) cells/2 kidneys to 18.2 ± 3.9 × 10(5) cells/2 kidneys (n = 6/group) when dietary NaCl was increased from 0.4 to 4.0%. Furthermore, the expression of immunoreactive p67(phox), gp91(phox), and p47(phox) subunits of NADPH oxidase was increased in T cells isolated from the kidneys of rats fed 4.0% NaCl. The urinary excretion of thiobarbituric acid-reactive substances (TBARS; an index of oxidative stress) also increased from 367 ± 49 to 688 ± 92 nmol/day (n = 8/group) when NaCl intake was increased in Dahl SS rats. Studies were then performed on rats treated with a daily injection of vehicle (5% dextrose) or tacrolimus (0.25 mg·kg(-1)·day(-1) ip), a calcineurin inhibitor that suppresses immune function, during the period of high-NaCl intake (n = 5/group). In contrast to the immune cell infiltration, increased NADPH oxidase expression, and elevated urine TBARS excretion in vehicle-treated Dahl SS fed high salt, these parameters were unaltered as NaCl intake was increased in Dahl SS rats administered tacrolimus. Moreover, tacrolimus treatment blunted high-salt mean arterial blood pressure and albumin excretion rate (152 ± 3 mmHg and 20 ± 9 mg/day, respectively) compared with values in dextrose-treated Dahl SS rats (171 ± 8 mmHg and 74 ± 28 mg/day). These experiments indicate that blockade of infiltrating immune cells is associated with decreased oxidative stress, an attenuation of hypertension, and a reduction of renal damage in Dahl SS rats fed high salt.

  15. Methylglyoxal increases dopamine level and leads to oxidative stress in SH-SY5Y cells.

    PubMed

    Xie, Bingjie; Lin, Fankai; Peng, Lei; Ullah, Kaleem; Wu, Hanyan; Qing, Hong; Deng, Yulin

    2014-11-01

    More and more studies have suggested that methylglyoxal (MGO) induced by type-2 diabetes is related to Parkinson's disease (PD). However, little is known about the molecular mechanism. In this study, we explored the MGO toxicity in neuroblastoma SH-SY5Y cells. Neurotoxicity of MGO was measured by mitochondrial membrane potential, malondialdehyde, and methylthiazoletetrazolium assays. The levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) were detected by liquid chromatography-mass spectrometry/mass spectrometry. The expressions of tyrosine hydroxylase (TH) and dopamine transporter (DAT) were detected by reverse transcriptase polymerase chain reaction and western blot analysis. The results showed that MGO induced an increase in TH and DAT expressions in SH-SY5Y neuroblastoma cells, while the levels of dopamine, DOPAC, and endogenous neurotoxin salsolinol also increased. Aminoguanidine (AG) is an inhibitor of MGO. It was found that AG could decrease the reactive oxygen species (ROS) level induced by MGO, but could not inhibit an increase of TH, DAT and dopamine. The increase of dopamine, DOPAC and salsolinol levels could lead to high ROS and mitochondrial damage. This study suggests that ROS caused by dopamine could contribute to the damage of dopaminergic neurons when MGO is increased during the course of diabetes.

  16. Catalase protects Aedes aegypti from oxidative stress and increases midgut infection prevalence of Dengue but not Zika.

    PubMed

    Oliveira, José Henrique M; Talyuli, Octávio A C; Goncalves, Renata L S; Paiva-Silva, Gabriela Oliveira; Sorgine, Marcos Henrique F; Alvarenga, Patricia Hessab; Oliveira, Pedro L

    2017-04-01

    Digestion of blood in the midgut of Aedes aegypti results in the release of pro-oxidant molecules that can be toxic to the mosquito. We hypothesized that after a blood meal, the antioxidant capacity of the midgut is increased to protect cells against oxidative stress. Concomitantly, pathogens present in the blood ingested by mosquitoes, such as the arboviruses Dengue and Zika, also have to overcome the same oxidative challenge, and the antioxidant program induced by the insect is likely to influence infection status of the mosquito and its vectorial competence. We found that blood-induced catalase mRNA and activity in the midgut peaked 24 h after feeding and returned to basal levels after the completion of digestion. RNAi-mediated silencing of catalase (AAEL013407-RB) reduced enzyme activity in the midgut epithelia, increased H2O2 leakage and decreased fecundity and lifespan when mosquitoes were fed H2O2. When infected with Dengue 4 and Zika virus, catalase-silenced mosquitoes showed no alteration in infection intensity (number of plaque forming units/midgut) 7 days after the infectious meal. However, catalase knockdown reduced Dengue 4, but not Zika, infection prevalence (percent of infected midguts). Here, we showed that blood ingestion triggers an antioxidant response in the midgut through the induction of catalase. This protection facilitates the establishment of Dengue virus in the midgut. Importantly, this mechanism appears to be specific for Dengue because catalase silencing did not change Zika virus prevalence. In summary, our data suggest that redox balance in the midgut modulates mosquito vectorial competence to arboviral infections.

  17. Anticonvulsant drugs, oxidative stress and nitric oxide.

    PubMed

    Vega Rasgado, L A; Ceballos Reyes, G M; Vega-Diaz, M F

    2011-01-01

    Nitric Oxide (NO) is thought to play a fundamental role in the genesis and the spreading of epileptiform hyperactivity, although its function is unclear and controversial. As a free radical, NO may cause oxidative stress, which is emerging as an important mechanism in the etiology of seizure-induced neuronal death. Here we investigated the role of NO in seizure mechanisms through oxidative stress generation by studying the effect of anticonvulsant drugs such as amino oxyacetic acid (AAOA), valproate (VALP), diazepam (DIAZ) and gabapentin (GBPTNA) on oxidative stress in the brain, estimated as free carbonyls by the method of Dalle and Rossi, and by measuring NO by the indirect method based on the Griess reaction. Results show that, except for AAOA and VALP, anticonvulsants did not significantly affect or decreased free carbonyls, but reversed the oxidative stress produced by pentylenetetrazole (PTZ) induced convulsions. Anticonvulsants except AAOA diminished NO levels and with the exception of VALP, counteracted the increase in NO generated by PTZ. Anticonvulsants decreased oxidative stress and NO especially in hippocampus (HI) and cortex (CX), and reversed PTZ effects on both parameters. PTZ diminished NO in HI, which could be explained since PTZ caused an increase on endothelial NO synthase but a decrease in neuronal NOS expression in this brain area. Since the drugs studied are modulating GABA levels, our results suggest that seizures generated by alterations in GABAergic transmission produce oxidative stress caused by NO, which can be reversed by anticonvulsants. The effects described differ among the brain regions studied and the NO synthase isoform affected.

  18. Does maternal exposure to artificial food coloring additives increase oxidative stress in the skin of rats?

    PubMed

    Başak, K; Başak, P Y; Doğuç, D K; Aylak, F; Oğuztüzün, S; Bozer, B M; Gültekin, F

    2016-11-16

    Glutathione-S-transferase (GST) and cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) metabolize and detoxify carcinogens, drugs, environmental pollutants, and reactive oxygen species. Changes of GST expression in tissues and gene mutations have been reported in association with many neoplastic skin diseases and dermatoses. Widely used artificial food coloring additives (AFCAs) also reported to effect primarily behavioral and cognitive function and cause neoplastic diseases and several inflammatory skin diseases. We aimed to identify the changes in expression of GSTs, CYP1A1, and vascular endothelial growth factor (VEGF) in rat skin which were maternally exposed AFCAs. A rat model was designed to evaluate the effects of maternal exposure of AFCAs on skin in rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Immunohistochemical expression of GSTs, CYP1A1, and VEGF was evaluated in their offspring. CYP1A1, glutathione S-transferase pi (GSTP), glutathione S-transferase alpha (GSTA), glutathione S-transferase mu (GSTM), glutathione S-transferase theta (GSTT), and VEGF were expressed by epidermal keratinocytes, dermal fibroblasts, sebaceous glands, hair follicle, and subcutaneous striated muscle in the normal skin. CYP1A1, GSTA, and GSTT were expressed at all microanatomical sites of skin in varying degrees. The expressions of CYP1A1, GSTA, GSTT, and VEGF were decreased significantly, while GSTM expression on sebaceous gland and hair follicle was increased. Maternal exposure of AFCAs apparently effects expression of the CYP1A1, GSTs, and VEGF in the skin. This prominent change of expressions might play role in neoplastic and nonneoplastic skin diseases.

  19. Increased oxidative stress in AOA3 cells disturbs ATM-dependent DNA damage responses.

    PubMed

    Kobayashi, Junya; Saito, Yuichiro; Okui, Michiyo; Miwa, Noriko; Komatsu, Kenshi

    2015-04-01

    Ataxia telangiectasia (AT) is caused by a mutation in the ataxia-telangiectasia-mutated (ATM) gene; the condition is associated with hyper-radiosensitivity, abnormal cell-cycle checkpoints, and genomic instability. AT patients also show cerebellar ataxia, possibly due to reactive oxygen species (ROS) sensitivity in neural cells. The ATM protein is a key regulator of the DNA damage response. Recently, several AT-like disorders have been reported. The genes responsible for them are predicted to encode proteins that interact with ATM in the DNA-damage response. Ataxia with oculomotor apraxia types 1-3 (AOA1, 2, and 3) result in a neurodegenerative and cellular phenotype similar to AT; however, the basis of this phenotypic similarity is unclear. Here, we show that the cells of AOA3 patients display aberrant ATM-dependent phosphorylation and apoptosis following γ-irradiation. The ATM-dependent response to H2O2 treatment was abrogated in AOA3 cells. Furthermore, AOA3 cells had reduced ATM activity. Our results suggest that the attenuated ATM-related response is caused by an increase in endogenous ROS in AOA3 cells. Pretreatment of cells with pyocyanin, which induces endogenous ROS production, abolished the ATM-dependent response. Moreover, AOA3 cells had decreased homologous recombination (HR) activity, and pyocyanin pretreatment reduced HR activity in HeLa cells. These results indicate that excess endogenous ROS represses the ATM-dependent cellular response and HR repair in AOA3 cells. Since the ATM-dependent cell-cycle checkpoint is an important block to carcinogenesis, such inactivation of ATM may lead to tumorigenesis as well as neurodegeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    SciTech Connect

    Simões, Maylla Ronacher; Aguado, Andrea; Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice; Zhenyukh, Olha; Briones, Ana María; Alonso, María Jesús; Vassallo, Dalton Valentim; Salaices, Mercedes

    2015-03-01

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  1. Pretreatment of the yeast antagonist, Candida oleophila with glycine betaine increases oxidative stress tolerance in the microenvironment of apple wounds

    USDA-ARS?s Scientific Manuscript database

    In response to wounding, harvested fruit tissues of apple and citrus exhibit the production of reactive oxygen species (ROS). ROS production is greater when yeast antagonists used as biocontrol agents are applied in the wounds. These phenomena result in an oxidative stress environment for the yeas...

  2. Ascorbate transport in pig coronary artery smooth muscle: Na(+) removal and oxidative stress increase loss of accumulated cellular ascorbate.

    PubMed

    Holmes, M E; Samson, S E; Wilson, J X; Dixon, S J; Grover, A K

    2000-01-01

    Pig deendothelialized coronary artery rings and smooth muscle cells cultured from them accumulated ascorbate from medium containing Na(+). The accumulated material was determined to be ascorbate using high-performance liquid chromatography. We further characterized ascorbate uptake in the cultured cells. The data fitted best with a Hill coefficient of 1 for ascorbate (K(asc) = 22 +/- 2 microM) and 2 for Na(+) (K(Na) = 84 +/- 10 mM). The anion transport inhibitors sulfinpyrazone and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) inhibited the uptake. Transferring cultured cells loaded with (14)C-ascorbate into an ascorbate-free solution resulted in a biphasic loss of radioactivity - an initial sulfinpyrazone-insensitive faster phase and a late sulfinpyrazone-sensitive slower phase. Transferring loaded cells into a Na(+)-free medium increased the loss in the initial phase in a sulfinpyrazone-sensitive manner, suggesting that the ascorbate transporter is bidirectional. Including peroxide or superoxide in the solution increased the loss of radioactivity. Thus, ascorbate accumulated in coronary artery smooth muscle cells by a Na(+)-dependent transporter was lost in an ascorbate-free solution, and the loss was increased by removing Na(+) from the medium or by oxidative stress.

  3. [The severity of gestational diabetes mellitus affects microvascular dysfunction measured three years after pregnancy that may be related to increased oxidative stress].

    PubMed

    Horváth, Eszter Mária; Mágenheim, Rita; Domján, Beatrix Annamária; Ferencz, Viktória; Tänczer, Tímea; Szabó, Eszter; Benkő, Rita; Szabó, Csaba; Tabák, Ádám; Somogyi, Anikó

    2015-11-22

    Oxidative-nitrative stress and poly(ADP-ribose) polymerase activation observed in gestational diabetes may play role in the increased cardiovascular risk in later life. The present study aimed to examine the influence of the severity of previous gestational diabetes (insulin need) on vascular function three years after delivery. Furthermore, the authors investigated the relation of vascular function with oxidative-nitrative stress and poly(ADP-ribose) polymerase activation. Macrovascular function was measured by applanation tonometry; microvascular reactivity was assessed by provocation tests during Laser-Doppler flowmetry in 40 women who had gestational diabetes 3 years before the study. Oxidative-nitrative stress and poly(ADP-ribose) polymerase activity in blood components were determined by colorimetry and immunohistochemistry. Three years after insulin treated gestational diabetes impaired microvascular function and increased oxidative stress was observed compared to mild cases. The severity of previous gestational diabetes affects microvascular dysfunction that is accompanied by elevated oxidative stress. Nitrative stress and poly(ADP-ribose) polymerase activity correlates with certain vascular factors not related to the severity of the disease.

  4. Levodopa increases oxidative stress and repulsive guidance molecule A levels: a pilot study in patients with Parkinson's disease.

    PubMed

    Müller, Thomas; Trommer, Isabel; Muhlack, Siegfried; Mueller, Bernhard K

    2016-04-01

    Exposure to free radicals influences synthesis, degradation and function of proteins, such as repulsive guidance molecule A. Decay of this protein is essential for neuronal maintenance and recovery. Levodopa elevates oxidative stress. Therefore levodopa may impact repulsive guidance molecule A metabolism. Objectives were to investigate plasma concentrations of repulsive guidance molecule A, levodopa, cysteine and cysteinyl-glycine before and 1 h after levodopa application in patients with Parkinson's disease. Cysteine and cysteinyl-glycine as biomarkers for oxidative stress exposure decreased, repulsive guidance molecule A and levodopa rose. Repulsive guidance molecule A remained unchanged in levodopa naïve patients, but particularly went up in patients on a prior chronic levodopa regimen. Decay of cysteine specifically cysteinyl-glycine results from an elevated glutathione generation with rising cysteine consumption respectively from the alternative glutathione transformation to its oxidized form glutathione disulfide after free radical scavenging. Repulsive guidance molecule A rise may inhibit physiologic mechanisms for neuronal survival.

  5. The metabolomics of oxidative stress.

    PubMed

    Noctor, Graham; Lelarge-Trouverie, Caroline; Mhamdi, Amna

    2015-04-01

    Oxidative stress resulting from increased availability of reactive oxygen species (ROS) is a key component of many responses of plants to challenging environmental conditions. The consequences for plant metabolism are complex and manifold. We review data on small compounds involved in oxidative stress, including ROS themselves and antioxidants and redox buffers in the membrane and soluble phases, and we discuss the wider consequences for plant primary and secondary metabolism. While metabolomics has been exploited in many studies on stress, there have been relatively few non-targeted studies focused on how metabolite signatures respond specifically to oxidative stress. As part of the discussion, we present results and reanalyze published datasets on metabolite profiles in catalase-deficient plants, which can be considered to be model oxidative stress systems. We emphasize the roles of ROS-triggered changes in metabolites as potential oxidative signals, and discuss responses that might be useful as markers for oxidative stress. Particular attention is paid to lipid-derived compounds, the status of antioxidants and antioxidant breakdown products, altered metabolism of amino acids, and the roles of phytohormone pathways.

  6. Staphylococcal response to oxidative stress

    PubMed Central

    Gaupp, Rosmarie; Ledala, Nagender; Somerville, Greg A.

    2012-01-01

    Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous oxidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, we summarize the cellular targets of oxidative stress, the mechanisms by which staphylococci sense oxidative stress and damage, oxidative stress protection and repair mechanisms, and regulation of the oxidative stress response. When possible, special attention is given to how the oxidative stress defense mechanisms help staphylococci control oxidative stress in the host. PMID:22919625

  7. Stress increases periodontal inflammation

    PubMed Central

    RIVERA, CÉSAR; MONSALVE, FRANCISCO; SUAZO, IVÁN; BECERRA, JAVIERA

    2012-01-01

    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1–1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P≤0.05, Mann-Whitney U-test) and increased the severity (P≤0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  8. Absence of aryl hydrocarbon receptors increases endogenous kynurenic acid levels and protects mouse brain against excitotoxic insult and oxidative stress.

    PubMed

    García-Lara, Lucia; Pérez-Severiano, Francisca; González-Esquivel, Dinora; Elizondo, Guillermo; Segovia, José

    2015-09-01

    L-kynurenine (Kyn) is a key element of tryptophan metabolism; it is enzymatically converted by kynurenine aminotransferase II (KAT II) to kynurenic acid (KYNA), which acts as an antagonist to the NMDA receptor-glycine site. Kyn is also an endogenous ligand of the aryl hydrocarbon receptor (AhR), a transcription factor that regulates the expression of a diverse set of genes. KYNA levels are reduced in several regions of the brain of Huntington's disease (HD) patients. The present work uses an AhR-null mouse and age-matched wild-type mice to determine the effect of the absence of AhR on KYNA availability. We found that, in AhR-null mice, there is an increase of KYNA levels in specific brain areas associated with higher expression of KAT II. Moreover, we induced an excitotoxic insult by intrastriatal administration of quinolinic acid, a biochemical model of HD, in both AhR-null and wild-type mice to evaluate the neurological damage as well as the oxidative stress caused by the lesion. The present work demonstrates that, in specific brain regions of AhR-null mice, the levels of KYNA are increased and that this induces a neuroprotective effect against neurotoxic insults. Moreover, AhR-null mice also show improved motor performance in the rotarod test, indicating a constitutive protection of striatal tissue. © 2015 Wiley Periodicals, Inc.

  9. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice

    PubMed Central

    Chupin, Stéphanie; Baron, Stéphanie; Nivet-Antoine, Valérie; Vessières, Emilie; Ayer, Audrey; Henrion, Daniel; Lenaers, Guy; Reynier, Pascal; Procaccio, Vincent

    2015-01-01

    Resveratrol is often described as a promising therapeutic molecule for numerous diseases, especially in metabolic and neurodegenerative disorders. While the mechanism of action is still debated, an increasing literature reports that resveratrol regulates the mitochondrial respiratory chain function. In a recent study we have identified mitochondrial complex I as a direct target of this molecule. Nevertheless, the mechanisms and consequences of such an interaction still require further investigation. In this study, we identified in silico by docking study a binding site for resveratrol at the nucleotide pocket of complex I. In vitro, using solubilized complex I, we demonstrated a competition between NAD+ and resveratrol. At low doses (<5μM), resveratrol stimulated complex I activity, whereas at high dose (50 μM) it rather decreased it. In vivo, in brain mitochondria from resveratrol treated young mice, we showed that complex I activity was increased, whereas the respiration rate was not improved. Moreover, in old mice with low antioxidant defenses, we demonstrated that complex I activation by resveratrol led to oxidative stress. These results bring new insights into the mechanism of action of resveratrol on mitochondria and highlight the importance of the balance between pro- and antioxidant effects of resveratrol depending on its dose and age. These parameters should be taken into account when clinical trials using resveratrol or analogues have to be designed. PMID:26684010

  10. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice.

    PubMed

    Gueguen, Naïg; Desquiret-Dumas, Valérie; Leman, Géraldine; Chupin, Stéphanie; Baron, Stéphanie; Nivet-Antoine, Valérie; Vessières, Emilie; Ayer, Audrey; Henrion, Daniel; Lenaers, Guy; Reynier, Pascal; Procaccio, Vincent

    2015-01-01

    Resveratrol is often described as a promising therapeutic molecule for numerous diseases, especially in metabolic and neurodegenerative disorders. While the mechanism of action is still debated, an increasing literature reports that resveratrol regulates the mitochondrial respiratory chain function. In a recent study we have identified mitochondrial complex I as a direct target of this molecule. Nevertheless, the mechanisms and consequences of such an interaction still require further investigation. In this study, we identified in silico by docking study a binding site for resveratrol at the nucleotide pocket of complex I. In vitro, using solubilized complex I, we demonstrated a competition between NAD+ and resveratrol. At low doses (<5μM), resveratrol stimulated complex I activity, whereas at high dose (50 μM) it rather decreased it. In vivo, in brain mitochondria from resveratrol treated young mice, we showed that complex I activity was increased, whereas the respiration rate was not improved. Moreover, in old mice with low antioxidant defenses, we demonstrated that complex I activation by resveratrol led to oxidative stress. These results bring new insights into the mechanism of action of resveratrol on mitochondria and highlight the importance of the balance between pro- and antioxidant effects of resveratrol depending on its dose and age. These parameters should be taken into account when clinical trials using resveratrol or analogues have to be designed.

  11. Does a resistance exercise session with continuous or intermittent blood flow restriction promote muscle damage and increase oxidative stress?

    PubMed

    Neto, Gabriel R; Novaes, Jefferson S; Salerno, Verônica P; Gonçalves, Michel M; Batista, Gilmário R; Cirilo-Sousa, Maria S

    2017-01-31

    The aim of this study was to compare the effect of low-load resistance exercise (LLRE) with continuous and intermittent blood flow restriction (BFR) on the creatine kinase (CK), lactate dehydrogenase (LDH), protein carbonyl (PC), thiobarbituric acid-reactive substance (TBARS) and uric acid (UA) levels in military men. The study included 10 recreationally trained men aged 19 ± 0.82 years who underwent the following experimental protocols in random order on separate days (72-96 h): 4 LLRE sessions at a 20% 1RM (one-repetition maximum [1RM]) with continuous BFR (LLRE + CBFR); 4 LLRE sessions at 20% 1RM with intermittent BFR (LLRE + IBFR) and 4 high-intensity resistance exercise (HIRE) sessions at 80% 1RM. The CK and LDH (markers of muscle damage) levels were measured before exercise (BE), 24 h post-exercise and 48 h post-exercise, and the PC, TBARS and UA (markers of oxidative stress) levels were measured BE and immediately after each exercise session. There was a significant increase in CK in the HIRE 24 post-exercise samples compared with the LLRE + CBFR and LLRE + IBFR (P = 0.035, P = 0.036, respectively), as well as between HIRE 48 post-exercise and LLRE + CBFR (P = 0.049). Additionally, there was a significant increase in CK in the LLRE + CBFR samples BE and immediately after each exercise (Δ = 21.9%) and in the HIRE samples BE and immediately after each exercise, BE and 24 post-exercise, and BE and 48 post-exercise (Δ values of 35%, 177.6%, and 177.6%, respectively). However, there were no significant changes in LDH, PC, TBARS, and UA between the protocols (P > 0.05). Therefore, a physical exercise session with continuous or intermittent BFR did not promote muscle damage; moreover, neither protocol seemed to affect the oxidative stress markers.

  12. Effect of increasing temperature in the differential activity of oxidative stress biomarkers in various tissues of the Rock goby, Gobius paganellus.

    PubMed

    Vinagre, Catarina; Madeira, Diana; Mendonça, Vanessa; Dias, Marta; Roma, Joana; Diniz, Mário S

    2014-06-01

    Oxidative stress biomarkers have been widely used in the development of ecological indices and in the assessment of exposure of aquatic organisms to contaminants from agricultural, industrial and urban pollution. However, temperature is known to also have a significant effect on oxidative stress biomarkers. This way, temperature is a confounding factor that may result in difficulties in the interpretation of oxidative stress biomarkers response patterns. Since climate change is expected to result in more frequent and intense heat wave events it is pertinent to investigate the effect of increasing temperature in the oxidative stress response of common aquatic organisms. It is also important to assess the differential response of different body tissues, given that they are differently exposed to temperature depending on their location and physiological function. This study investigates the effect of increasing temperature (20 °C-34 °C) in the response of multiple biomarkers of oxidative stress: lipid peroxidation, glutathione-S-transferase, superoxide dismutase and catalase activities, in the muscle, liver and gills of a common coastal fish, the Rock goby, Gobius paganellus. The response of the oxidative stress biomarkers analysed were always higher in the gills than in the other tissues. Muscle generally presented the lower levels of any of the biomarkers tested when compared to other tissues. Nevertheless, muscle tissue always responded significantly to temperature, as did the liver, while the gills were unresponsive in terms of lipid peroxidation and glutathione-S-transferase. Unresponsive tissues to temperature may be particularly interesting as indicators of pollution, given that temperature will not be a confounding variable in their oxidative stress response. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Erythropoietin and oxidative stress.

    PubMed

    Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen

    2008-05-01

    Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor kappaB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care.

  14. Metallothionein disulfides are present in metallothionein-overexpressing transgenic mouse heart and increase under conditions of oxidative stress.

    PubMed

    Feng, Wenke; Benz, Frederick W; Cai, Jian; Pierce, William M; Kang, Y James

    2006-01-13

    Metallothionein (MT) releases zinc under oxidative stress conditions in cultured cells. The change in the MT molecule after zinc release in vivo is unknown although in vitro studies have identified MT disulfide bond formation. The present study was undertaken to test the hypothesis that MT disulfide bond formation occurs in vivo. A cardiac-specific MT-overexpressing transgenic mouse model was used. Mice were administered saline as a control or doxorubicin (20 mg/kg), which is an effective anticancer drug but with severe cardiac toxicity at least partially because of the generation of reactive oxygen species. A differential alkylation of cysteine residues in MT of the heart extracts was performed. Free and metal-bound cysteines were first trapped by N-ethylmaleimide and the disulfide bonds were reduced by dithiothreitol followed by alkylation with radiolabeled iodoacetamide. Analyses of the differentially alkylated MTs in the heart extract by high performance liquid chromatography, SDS-PAGE, Western blot, and mass spectrometry revealed that disulfide bonds were present in MT in vivo under both physiological and oxidative stress conditions. More disulfide bonds were found in MT under the oxidative stress conditions. The MT disulfide bonds were likely intramolecular and both alpha- and beta-domains were involved in the disulfide bond formation, although the alpha-domain appeared to be more easily oxidized than the beta-domain. The results suggest that under physiological conditions, the formation of MT disulfide bonds is involved in the regulation of zinc homeostasis. Additional zinc release from MT under oxidative stress conditions is accompanied by more MT disulfide bond formation.

  15. Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP-1c in L-02 Cells.

    PubMed

    Qin, Shumin; Yin, Jinjin; Huang, Keer

    2016-07-01

    Excessive fat accumulation and increased oxidative stress contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the development of steatosis are not entirely understood. The present study was undertaken to establish an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the effects of oxidative stress could be studied in L-02 cells. We investigated the effects of free fatty acids (FFA) (palmitate:oleate, 1:2) on lipid accumulation and oxidative stress and their possible mechanisms in L-02 cells. High concentrations of fatty acids significantly induced excessive lipid accumulation and oxidative stress in L-02 cells, which could only be reversed with 50 μΜ WY14643 (the PPARα agonist). Immunoblotting and qPCR analyses revealed that FFA downregulated the expression of proliferator-activated receptor alpha (PPARα), which contributed to the increased activation of sterol regulatory element binding protein-1c (SREBP-1c). These results suggest that FFA induce lipid accumulation and oxidative stress in L-02 cells by upregulating SREBP-1c expression through the suppression of PPARα.

  16. Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function.

    PubMed

    Hernanz, Raquel; Martín, Ángela; Pérez-Girón, Jose V; Palacios, Roberto; Briones, Ana M; Miguel, Marta; Salaices, Mercedes; Alonso, María J

    2012-06-01

    PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved. Mesenteric resistance arteries from untreated or pioglitazone-treated (2.5 mg·kg⁻¹ ·day⁻¹ , 28 days) SHR and normotensive [Wistar Kyoto (WKY)] rats were used. Vascular structure was studied by pressure myography, vascular function by wire myography, protein expression by Western blot and immunohistochemistry, mRNA levels by RT-PCR, prostanoid levels by commercial kits and reactive oxygen species (ROS) production by dihydroethidium-emitted fluorescence. In SHR, pioglitazone did not modify either BP or vascular structural and mechanical alterations or phenylephrine-induced contraction, but it increased vascular COX-2 levels, prostacyclin (PGI₂) production and the inhibitory effects of NS 398, SQ 29,548 and tranylcypromine on phenylephrine responses. The contractile phase of the iloprost response, which was reduced by SQ 29,548, was greater in pioglitazone-treated and pioglitazone-untreated SHR than WKY. In addition, pioglitazone abolished the increased vascular ROS production, NOX-1 levels and the inhibitory effect of apocynin and allopurinol on phenylephrine contraction, whereas it did not modify eNOS expression but restored the potentiating effect of N-nitro-L-arginine methyl ester on phenylephrine responses. Although pioglitazone did not reduce BP in SHR, it increased COX-2-derived PGI₂ production, reduced oxidative stress, and increased NO bioavailability, which are all involved in vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. © 2012 The Authors. British Journal of Pharmacology © 2012 The British

  17. Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function

    PubMed Central

    Hernanz, Raquel; Martín, Ángela; Pérez-Girón, Jose V; Palacios, Roberto; Briones, Ana M; Miguel, Marta; Salaices, Mercedes; Alonso, María J

    2012-01-01

    BACKGROUND AND PURPOSE PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved. EXPERIMENTAL APPROACH Mesenteric resistance arteries from untreated or pioglitazone-treated (2.5 mg·kg−1·day−1, 28 days) SHR and normotensive [Wistar Kyoto (WKY)] rats were used. Vascular structure was studied by pressure myography, vascular function by wire myography, protein expression by Western blot and immunohistochemistry, mRNA levels by RT-PCR, prostanoid levels by commercial kits and reactive oxygen species (ROS) production by dihydroethidium-emitted fluorescence. KEY RESULTS In SHR, pioglitazone did not modify either BP or vascular structural and mechanical alterations or phenylephrine-induced contraction, but it increased vascular COX-2 levels, prostacyclin (PGI2) production and the inhibitory effects of NS 398, SQ 29,548 and tranylcypromine on phenylephrine responses. The contractile phase of the iloprost response, which was reduced by SQ 29,548, was greater in pioglitazone-treated and pioglitazone-untreated SHR than WKY. In addition, pioglitazone abolished the increased vascular ROS production, NOX-1 levels and the inhibitory effect of apocynin and allopurinol on phenylephrine contraction, whereas it did not modify eNOS expression but restored the potentiating effect of N-nitro-L-arginine methyl ester on phenylephrine responses. CONCLUSIONS AND IMPLICATIONS Although pioglitazone did not reduce BP in SHR, it increased COX-2-derived PGI2 production, reduced oxidative stress, and increased NO bioavailability, which are all involved in vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. PMID

  18. Oxidative stress alters base excision repair pathway and increases apoptotic response in Apurinic/apyrimidinic endonuclease 1/Redox factor-1 haploinsufficient mice

    PubMed Central

    Unnikrishnan, Archana; Raffoul, Julian J.; Patel, Hiral V.; Prychitko, Thomas M.; Anyangwe, Njwen; Meira, Lisiane B.; Friedberg, Errol C.; Cabelof, Diane C.; Heydari, Ahmad R.

    2009-01-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-κB, and the major 5’-endonuclease in base excision repair (BER). We utilized mice containing heterozygous gene-targeted deletion of APE1/Ref-1 (Apex+/-) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency results in a significant decline in NF-κB DNA binding activity in response to oxidative stress in liver. In addition, loss of APE1/Ref-1 increases the apoptotic response to oxidative stress where a significant increase in GADD45g expression, p53 protein stability and caspase activity are observed. Oxidative stress displays a differential impact on monofunctional (UDG) and bifunctional (OGG1) DNA glycosylase initiated BER in liver of Apex+/- mice. APE1/Ref-1 haploinsufficiency results in a significant decline in the repair of oxidized bases (e.g., 8-OHdG), while removal of uracil is increased in liver nuclear extracts of mice using an in vitro BER assay. Apex+/- mice exposed to 2-NP displayed a significant decline in 3’-OH-containing single-strand breaks and an increase in aldehydic lesions in their liver DNA suggesting an accumulation of repair intermediates of failed bifunctional DNA glycosylase initiated BER. PMID:19268524

  19. p53, Oxidative Stress, and Aging

    PubMed Central

    Liu, Dongping

    2011-01-01

    Abstract Mammalian aging is associated with elevated levels of oxidative damage of DNA, proteins, and lipids as a result of unbalanced prooxidant and antioxidant activities. Accumulating evidence indicates that oxidative stress is a major physiological inducer of aging. p53, the guardian of the genome that is important for cellular responses to oxidative stresses, might be a key coordinator of oxidative stress and aging. In response to low levels of oxidative stresses, p53 exhibits antioxidant activities to eliminate oxidative stress and ensure cell survival; in response to high levels of oxidative stresses, p53 exhibits prooxidative activities that further increase the levels of stresses, leading to cell death. p53 accomplishes these context-dependent roles by regulating the expression of a panel of genes involved in cellular responses to oxidative stresses and by modulating other pathways important for oxidative stress responses. The mechanism that switches p53 function from antioxidant to prooxidant remains unclear, but could account for the findings that increased p53 activities have been linked to both accelerated aging and increased life span in mice. Therefore, a balance of p53 antioxidant and prooxidant activities in response to oxidative stresses could be important for longevity by suppressing the accumulation of oxidative stresses and DNA damage. Antioxid. Redox Signal. 15, 1669–1678. PMID:21050134

  20. The cyanobacterial hepatotoxin microcystin binds to proteins and increases the fitness of microcystis under oxidative stress conditions.

    PubMed

    Zilliges, Yvonne; Kehr, Jan-Christoph; Meissner, Sven; Ishida, Keishi; Mikkat, Stefan; Hagemann, Martin; Kaplan, Aaron; Börner, Thomas; Dittmann, Elke

    2011-03-18

    Microcystins are cyanobacterial toxins that represent a serious threat to drinking water and recreational lakes worldwide. Here, we show that microcystin fulfils an important function within cells of its natural producer Microcystis. The microcystin deficient mutant ΔmcyB showed significant changes in the accumulation of proteins, including several enzymes of the Calvin cycle, phycobiliproteins and two NADPH-dependent reductases. We have discovered that microcystin binds to a number of these proteins in vivo and that the binding is strongly enhanced under high light and oxidative stress conditions. The nature of this binding was studied using extracts of a microcystin-deficient mutant in vitro. The data obtained provided clear evidence for a covalent interaction of the toxin with cysteine residues of proteins. A detailed investigation of one of the binding partners, the large subunit of RubisCO showed a lower susceptibility to proteases in the presence of microcystin in the wild type. Finally, the mutant defective in microcystin production exhibited a clearly increased sensitivity under high light conditions and after hydrogen peroxide treatment. Taken together, our data suggest a protein-modulating role for microcystin within the producing cell, which represents a new addition to the catalogue of functions that have been discussed for microbial secondary metabolites.

  1. High salt diet impairs memory-related synaptic plasticity via increased oxidative stress and suppressed synaptic protein expression.

    PubMed

    Ge, Qian; Wang, Zhengjun; Wu, Yuwei; Huo, Qing; Qian, Zhaoqiang; Tian, Zhongmin; Ren, Wei; Zhang, Xia; Han, Jing

    2017-10-01

    A high salt (HS) diet is detrimental to cognitive function, in addition to having a role in cardiovascular disorders. However, the method by which an HS diet impairs cognitive functions such as learning and memory remains open. In this study, we found that mice on a 7 week HS diet demonstrated disturbed short-term memory in an object-place recognition task, and both 4 week and 7 week HS treatments impaired long-term memory, as evidenced in a fear conditioning test. Mechanistically, the HS diet inhibited memory-related long-term potentiation (LTP) in the hippocampus, while also increasing the levels of reactive oxygen species (ROS) in hippocampal cells and downregulating the expression of synapsin I, synaptophysin, and brain-derived neurotrophic factor in specific encephalic region. This suggests that oxidative stress or synaptic protein/neurotrophin deregulation was involved in the HS diet-induced memory impairment. Thus, the present study provides novel insights into the mechanisms of memory impairment caused by excessive dietary salt, and underlined the importance of controlling to salt absorb quantity. © 2017 The Authors. Molecular Nutrition & Food Research Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Indocyanine green increases light-induced oxidative stress, senescence, and matrix metalloproteinases 1 and 3 in human RPE cells.

    PubMed

    Kernt, Marcus; Hirneiss, Christoph; Wolf, Armin; Liegl, Raffael; Rueping, Johann; Neubauer, Aljoscha; Alge, Claudia; Ulbig, Michael; Gandorfer, Arndt; Kampik, Anselm; Haritoglou, Christos

    2012-09-01

    Indocyanine green (ICG) is a commonly used vital dye for macular surgery. Recent reports implicate that its use might be associated with less favourable results regarding postoperative visual outcome and damage of retinal cells, and atrophic degeneration of the retinal pigment epithelium (RPE) has been described. This study investigates the effects of ICG on light-induced senescence of RPE cells. Primary human RPE cells were either pre-incubated with ICG in concentrations of 0.005% and 0.05% or not and then exposed to white light. After 10 min of irradiation viability, induction of intracellular reactive oxygen species (ROS) and senescence-associated β-galactosidase activity (SA β-Gal) were determined. Expression and secretion of matrix metalloproteinases (MMPs) 1 and 3 and their mRNA were determined by RT-PCR and ELISA. Light exposure decreased RPE cell viability by 46%. Treatment with 0.005% and 0.05% ICG alone decreased RPE cell viability by 7% and 21%. In addition, expression of ROS, SA β-Gal, and MMP-1 and 3 was significantly increased. When 0.005% and 0.05% ICG treatments were combined with light exposure, viability decreased by 69% and 82% compared to the untreated control. Effects on the expression of ROS, SA β-Gal, and MMP-1 and 3 were, depending on the ICG dose, significantly increased when cells were pre-incubated with ICG and then illuminated. In this study, pretreatment with ICG significantly increased light-induced oxidative stress and senescence. This might indicate a potential, supplementary mechanism that could explain RPE alterations and reduced functional results after ICG-assisted internal limiting membrane peeling. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

  3. Oxidative stress increased hepatotoxicity induced by nano-titanium dioxide in BRL-3A cells and Sprague-Dawley rats.

    PubMed

    Sha, Baoyong; Gao, Wei; Wang, Shuqi; Gou, Xingchun; Li, Wei; Liang, Xuan; Qu, Zhiguo; Xu, Feng; Lu, Tian Jian

    2014-04-01

    Extensive studies have shown that titanium dioxide (TiO2 ) nanomaterials (NMs) can cause toxicity in vitro and in vivo under normal conditions. However, an adverse effect induced by nano-TiO2 in many diseased conditions, typically characterized by oxidative stress (OS), remains unknown. We investigated the toxicity of nano-TiO2 in rat liver cells (BRL-3A) and Sprague-Dawley (SD) rat livers under OS conditions, which were generated using hydrogen peroxide (H2 O2 ) in vitro and alloxan in vivo, respectively. In vitro results showed that cell death ratios after nano-TiO2 exposure were significantly enhanced (up to 2.62-fold) in BRL-3A cells under OS conditions, compared with normal controls. Significant interactions between OS conditions and nano-TiO2 resulted in the rapid G0/G1 to S phase transition and G2/M arrest, which were opposite to G0/G1 phase arrest in cells after NMs exposure only. In vivo results showed that obvious pathological changes in rat livers and the increased activities of four enzymes (i.e. aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase) owing to liver damage after nano-TiO2 exposure under OS conditions, compared with their healthy controls. In addition, compared with increased hepatotoxicity after nano-TiO2 exposure, micro-TiO2 showed no adverse effects to cells and rat livers under OS conditions. Our results suggested that OS conditions synergistically increase nano-TiO2 induced toxicity in vitro and in vivo, indicating that the evaluation of nanotoxicity under OS conditions is essentially needed prior to various applications of NMs in foods, cosmetics and potential treatment of diseases.

  4. Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats.

    PubMed

    Moreira, Josimar D; Pernomian, Larissa; Gomes, Mayara S; Moreira, Rafael P; do Prado, Alejandro F; da Silva, Carlos H T P; de Oliveira, Ana M

    2016-07-15

    Diabetes mellitus is associated with reactive oxygen and nitrogen species accumulation. Behavioral stress increases nitric oxide production, which may trigger a massive impact on vascular cells and accelerate cardiovascular complications under oxidative stress conditions such as Diabetes. For this study, type-1 Diabetes mellitus was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration-response curves for angiotensin II were obtained in endothelium-intact carotid rings from diabetic rats that underwent to acute restraint stress for 3h. The contractile response evoked by angiotensin II was increased in carotid arteries from diabetic rats. Acute restraint stress did not alter angiotensin II-induced contraction in carotid arteries from normoglycaemic rats. However acute stress combined with Diabetes increased angiotensin II-induced contraction in carotid rings. Western blot experiments and the inhibition of nitric oxide synthases in functional assays showed that neuronal, endothelial and inducible nitric oxide synthase isoforms contribute to the increased formation of peroxynitrite and contractile hyperreactivity to angiotensin II in carotid rings from stressed diabetic rats. In summary, these findings suggest that the increased superoxide anion generation in carotid arteries from diabetic rats associated to the increased local nitric oxide synthases expression and activity induced by acute restrain stress were responsible for exacerbating the local formation of peroxynitrite and the contraction induced by angiotensin II. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Liver metabolomics reveals increased oxidative stress and fibrogenic potential in gfrp transgenic mice in response to ionizing radiation.

    PubMed

    Cheema, Amrita K; Pathak, Rupak; Zandkarimi, Fereshteh; Kaur, Prabhjit; Alkhalil, Lynn; Singh, Rajbir; Zhong, Xiaogang; Ghosh, Sanchita; Aykin-Burns, Nukhet; Hauer-Jensen, Martin

    2014-06-06

    Although radiation-induced tissue-specific injury is well documented, the underlying molecular changes resulting in organ dysfunction and the consequences thereof on overall metabolism and physiology have not been elucidated. We previously reported the generation and characterization of a transgenic mouse strain that ubiquitously overexpresses Gfrp (GTPH-1 feedback regulatory protein) and exhibits higher oxidative stress, which is a possible result of decreased tetrahydrobiopterin (BH4) bioavailability. In this study, we report genotype-dependent changes in the metabolic profiles of liver tissue after exposure to nonlethal doses of ionizing radiation. Using a combination of untargeted and targeted quantitative mass spectrometry, we report significant accumulation of metabolites associated with oxidative stress, as well as the dysregulation of lipid metabolism in transgenic mice after radiation exposure. The radiation stress seems to exacerbate lipid peroxidation and also results in higher expression of genes that facilitate liver fibrosis, in a manner that is dependent on the genetic background and post-irradiation time interval. These findings suggest the significance of Gfrp in regulating redox homeostasis in response to stress induced by ionizing radiation affecting overall physiology.

  6. Liver Metabolomics Reveals Increased Oxidative Stress and Fibrogenic Potential in Gfrp Transgenic Mice in Response to Ionizing Radiation

    PubMed Central

    2015-01-01

    Although radiation-induced tissue-specific injury is well documented, the underlying molecular changes resulting in organ dysfunction and the consequences thereof on overall metabolism and physiology have not been elucidated. We previously reported the generation and characterization of a transgenic mouse strain that ubiquitously overexpresses Gfrp (GTPH-1 feedback regulatory protein) and exhibits higher oxidative stress, which is a possible result of decreased tetrahydrobiopterin (BH4) bioavailability. In this study, we report genotype-dependent changes in the metabolic profiles of liver tissue after exposure to nonlethal doses of ionizing radiation. Using a combination of untargeted and targeted quantitative mass spectrometry, we report significant accumulation of metabolites associated with oxidative stress, as well as the dysregulation of lipid metabolism in transgenic mice after radiation exposure. The radiation stress seems to exacerbate lipid peroxidation and also results in higher expression of genes that facilitate liver fibrosis, in a manner that is dependent on the genetic background and post-irradiation time interval. These findings suggest the significance of Gfrp in regulating redox homeostasis in response to stress induced by ionizing radiation affecting overall physiology. PMID:24824572

  7. Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease.

    PubMed

    Mohmmad Abdul, Hafiz; Sultana, Rukhsana; Keller, Jeffrey N; St Clair, Daret K; Markesbery, William R; Butterfield, D Allan

    2006-03-01

    Oxidative stress is observed in Alzheimer's disease (AD) brain, including protein oxidation and lipid peroxidation. One of the major pathological hallmarks of AD is the brain deposition of amyloid beta-peptide (Abeta). This 42-mer peptide is derived from the beta-amyloid precursor protein (APP) and is associated with oxidative stress in vitro and in vivo. Mutations in the PS-1 and APP genes, which increase production of the highly amyloidogenic amyloid beta-peptide (Abeta42), are the major causes of early onset familial AD. Several lines of evidence suggest that enhanced oxidative stress, inflammation, and apoptosis play important roles in the pathogenesis of AD. In the present study, primary neuronal cultures from knock-in mice expressing mutant human PS-1 and APP were compared with those from wild-type mice, in the presence or absence of various oxidizing agents, viz, Abeta(1-42), H2O2 and kainic acid (KA). APP/PS-1 double mutant neurons displayed a significant basal increase in oxidative stress as measured by protein oxidation, lipid peroxidation, and 3-nitrotyrosine when compared with the wild-type neurons (p < 0.0005). Elevated levels of human APP, PS-1 and Abeta(1-42) were found in APP/PS-1 cultures compared with wild-type neurons. APP/PS-1 double mutant neuron cultures exhibited increased vulnerability to oxidative stress, mitochondrial dysfunction and apoptosis induced by Abeta(1-42), H2O2 and KA compared with wild-type neuronal cultures. The results are consonant with the hypothesis that Abeta(1-42)-associated oxidative stress and increased vulnerability to oxidative stress may contribute significantly to neuronal apoptosis and death in familial early onset AD.

  8. Impaired Corpus Cavernosum Relaxation Is Accompanied by Increased Oxidative Stress and Up-Regulation of the Rho-Kinase Pathway in Diabetic (Db/Db) Mice.

    PubMed

    Priviero, Fernanda B M; Toque, Haroldo A F; Nunes, Kenia Pedrosa; Priolli, Denise G; Teixeira, Cleber E; Webb, R Clinton

    2016-01-01

    Basal release of nitric oxide from endothelial cells modulates contractile activity in the corpus cavernosum via inhibition of the RhoA/Rho-kinase signaling pathway. We aimed to investigate nitric oxide bioavailability, oxidative stress and the Rho-kinase pathway in the relaxation of the corpus cavernosum of an obese and diabetic model of mice (db/db mice). We hypothesized that in db/db mice impaired relaxation induced by Rho-kinase inhibitor is accompanied by diminished NO bioavailability, increased oxidative stress and upregulation of the RhoA/Rho-kinase signalling pathway. Cavernosal strips from male lean and non-diabetic db/+ and db/db mice were mounted in myographs and isometric force in response to Rho-kinase inhibitor Y-27632 was recorded. Enzyme activity and protein expression of oxidative stress markers and key molecules of the RhoA/Rho-kinase pathway were analyzed. The Rho-kinase inhibitor Y-27632 concentration-dependently caused corpus cavernosum relaxation and inhibited cavernosal contractions. Nonetheless, a rightward shift in the curves obtained in corpus cavernosum of db/db mice was observed. Compared to db/+, this strain presented increased active RhoA, higher MYPT-1 phosphorylation stimulated by phenylephrine, and increased expression of ROKα and Rho-GEFs. Further, we observed normal expression of endothelial and neuronal NOS in corpus cavernosum of db/db mice. However, nitrate/nitrate (NOx) levels were diminished, suggesting decreased NO bioavailability. We measured the oxidant status and observed increased lipid peroxidation, with decreased SOD activity and expression. In conclusion, our data demonstrate that in db/db mice, upregulation of the RhoA/Rho-kinase signalling pathway was accompanied by decreased NO bioavailability and increased oxidative stress contributing to impaired relaxation of the corpus cavermosum of db/db mice.

  9. Impaired Corpus Cavernosum Relaxation Is Accompanied by Increased Oxidative Stress and Up-Regulation of the Rho-Kinase Pathway in Diabetic (Db/Db) Mice

    PubMed Central

    Priviero, Fernanda B. M.; Toque, Haroldo A. F.; Nunes, Kenia Pedrosa; Priolli, Denise G.; Webb, R. Clinton

    2016-01-01

    Basal release of nitric oxide from endothelial cells modulates contractile activity in the corpus cavernosum via inhibition of the RhoA/Rho-kinase signaling pathway. We aimed to investigate nitric oxide bioavailability, oxidative stress and the Rho-kinase pathway in the relaxation of the corpus cavernosum of an obese and diabetic model of mice (db/db mice). We hypothesized that in db/db mice impaired relaxation induced by Rho-kinase inhibitor is accompanied by diminished NO bioavailability, increased oxidative stress and upregulation of the RhoA/Rho-kinase signalling pathway. Cavernosal strips from male lean and non-diabetic db/+ and db/db mice were mounted in myographs and isometric force in response to Rho-kinase inhibitor Y-27632 was recorded. Enzyme activity and protein expression of oxidative stress markers and key molecules of the RhoA/Rho-kinase pathway were analyzed. The Rho-kinase inhibitor Y-27632 concentration-dependently caused corpus cavernosum relaxation and inhibited cavernosal contractions. Nonetheless, a rightward shift in the curves obtained in corpus cavernosum of db/db mice was observed. Compared to db/+, this strain presented increased active RhoA, higher MYPT-1 phosphorylation stimulated by phenylephrine, and increased expression of ROKα and Rho-GEFs. Further, we observed normal expression of endothelial and neuronal NOS in corpus cavernosum of db/db mice. However, nitrate/nitrate (NOx) levels were diminished, suggesting decreased NO bioavailability. We measured the oxidant status and observed increased lipid peroxidation, with decreased SOD activity and expression. In conclusion, our data demonstrate that in db/db mice, upregulation of the RhoA/Rho-kinase signalling pathway was accompanied by decreased NO bioavailability and increased oxidative stress contributing to impaired relaxation of the corpus cavermosum of db/db mice. PMID:27227463

  10. High dietary iron increases oxidative stress and radiosensitivity in the rat retina and vasculature after exposure to fractionated gamma radiation

    PubMed Central

    Theriot, Corey A; Westby, Christian M; Morgan, Jennifer L L; Zwart, Sara R; Zanello, Susana B

    2016-01-01

    Radiation exposure in combination with other space environmental factors including microgravity, nutritional status, and deconditioning is a concern for long-duration space exploration missions. Astronauts experience altered iron homeostasis due to adaptations to microgravity and an iron-rich food system. Iron intake reaches three to six times the recommended daily allowance due to the use of fortified foods on the International Space Station. Iron is associated with certain optic neuropathies and can potentiate oxidative stress. This study examined the response of eye and vascular tissue to gamma radiation exposure (3 Gy fractionated at 37.5 cGy per day every other day for 8 fractions) in rats fed an adequate-iron diet or a high-iron diet. Twelve-week-old Sprague-Dawley rats were assigned to one of four experimental groups: adequate-iron diet/no radiation (CON), high-iron diet/no radiation (IRON), adequate-iron diet/radiation (RAD), and high-iron diet/radiation (IRON+RAD). Animals were maintained on the corresponding iron diet for 2 weeks before radiation exposure. As previously published, the high-iron diet resulted in elevated blood and liver iron levels. Dietary iron overload altered the radiation response observed in serum analytes, as evidenced by a significant increase in catalase levels and smaller decrease in glutathione peroxidase and total antioxidant capacity levels. 8-OHdG immunostaining, showed increased intensity in the retina after radiation exposure. Gene expression profiles of retinal and aortic vascular samples suggested an interaction between the response to radiation and high dietary iron. This study suggests that the combination of gamma radiation and high dietary iron has deleterious effects on retinal and vascular health and physiology. PMID:28725729

  11. Triclosan, an antibacterial agent, increases intracellular Zn(2+) concentration in rat thymocytes: its relation to oxidative stress.

    PubMed

    Tamura, Ikumi; Kanbara, Yasuhiro; Saito, Minoru; Horimoto, Kanna; Satoh, Masaya; Yamamoto, Hiroshi; Oyama, Yasuo

    2012-01-01

    Triclosan is used as an antibacterial agent in household items and personal care products. Since this compound is found in maternal milk of humans and bodies of wild animals, there is growing concern among some consumer groups and scientific community that triclosan is adverse for humans and wild animals. In order to estimate adverse actions of triclosan, the effects of triclosan on intracellular Zn(2+) concentration and cellular thiol content were studied in rat thymocytes by the use of flow cytometer with appropriate fluorescent probes. Triclosan at 1-3 μM (sublethal concentrations) increased the intensity of FluoZin-3 fluorescence (intracellular Zn(2+) concentration) and decreased the intensity of 5-chloromethylfluorescein (5-CMF) fluorescence (cellular thiol content). Negative correlation (r=-0.985) between triclosan-induced changes in FluoZin-3 and 5-CMF fluorescences was found. Removal of external Zn(2+) did not significantly affect the triclosan-induced augmentation of FluoZin-3 fluorescence, suggesting an intracellular Zn(2+) release by triclosan. These actions of triclosan were similar to those of H(2)O(2) and triclosan significantly potentiated the cytotoxicity of H(2)O(2). Therefore, the results may suggest that triclosan at sublethal concentrations induces oxidative stress that decreases cellular thiol content, resulting in an increase in intracellular Zn(2+) concentration by Zn(2+) release from intracellular store(s). Since recent studies show many physiological roles of intracellular Zn(2+) in cellular functions, the triclosan-induced disturbance of cellular Zn(2+) homeostasis may induce adverse actions on the cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Space flight and oxidative stress

    NASA Technical Reports Server (NTRS)

    Stein, T. P.

    2002-01-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

  13. Space flight and oxidative stress.

    PubMed

    Stein, T P

    2002-10-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

  14. Space flight and oxidative stress

    NASA Technical Reports Server (NTRS)

    Stein, T. P.

    2002-01-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

  15. Ablation of the Locus Coeruleus Increases Oxidative Stress in Tg-2576 Transgenic but Not Wild-Type Mice

    PubMed Central

    Hurko, Orest; Boudonck, Kurt; Gonzales, Cathleen; Hughes, Zoe A.; Jacobsen, J. Steve; Reinhart, Peter H.; Crowther, Daniel

    2010-01-01

    Mice transgenic for production of excessive or mutant forms of beta-amyloid differ from patients with Alzheimer's disease in the degree of inflammation, oxidative damage, and alteration of intermediary metabolism, as well as the paucity or absence of neuronal atrophy and cognitive impairment. Previous observers have suggested that differences in inflammatory response reflect a discrepancy in the state of the locus coeruleus (LC), loss of which is an early change in Alzheimer's disease but which is preserved in the transgenic mice. In this paper, we extend these observations by examining the effects of the LC on markers of oxidative stress and intermediary metabolism. We compare four groups: wild-type or Tg2576 Aβ transgenic mice injected with DSP4 or vehicle. Of greatest interest were metabolites different between ablated and intact transgenics, but not between ablated and intact wild-type animals. The Tg2576_DSP4 mice were distinguished from the other three groups by oxidative stress and altered energy metabolism. These observations provide further support for the hypothesis that Tg2576 Aβ transgenic mice with this ablation may be a more congruent model of Alzheimer's disease than are transgenics with an intact LC. PMID:20981353

  16. 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

  17. Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

    PubMed Central

    Silva, Maísa; Guerra, Joyce Ferreira da Costa; Sampaio, Ana Flávia Santos; de Lima, Wanderson Geraldo; Silva, Marcelo Eustáquio

    2015-01-01

    The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S), which was fed the AIN-93M diet, and the standard plus iron group (SI), which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress. PMID:25685776

  18. Oxidative Stress and Psychological Disorders

    PubMed Central

    Salim, Samina

    2014-01-01

    Oxidative stress is an imbalance between cellular production of reactive oxygen species and the counteracting antioxidant mechanisms. The brain with its high oxygen consumption and a lipid-rich environment is considered highly susceptible to oxidative stress or redox imbalances. Therefore, the fact that oxidative stress is implicated in several mental disorders including depression, anxiety disorders, schizophrenia and bipolar disorder, is not surprising. Although several elegant studies have established a link between oxidative stress and psychiatric disorders, the causal relationship between oxidative stress and psychiatric diseases is not fully determined. Another critical aspect that needs much attention and effort is our understanding of the association between cellular oxidative stress and emotional stress. This review examines some of the recent discoveries that link oxidative status with anxiety, depression, schizophrenia and bipolar disorder. A discussion of published results and questions that currently exist in the field regarding a causal relationship between oxidative and emotional stress is also provided. PMID:24669208

  19. Chronic emotional stress exposure increases infarct size in rats: the role of oxidative and nitrosative damage in response to sympathetic hyperactivity.

    PubMed

    Mercanoglu, G; Safran, N; Uzun, H; Eroglu, L

    2008-12-01

    We investigated the level of sympathetic hyperactivity in response to stress exposure in an acute myocardial infarction (AMI) model and the contribution of oxidative and nitrosative damage to this phenomenon. Stress was induced by 20-day administration of different emotional stress factors: daylight/darkness exposure, overcrowding, isolation, new hierarchy, tilting the cage and restriction of water or food. AMI was induced surgically. Heart rate (HR) and heart rate variability (HRV) measurements were done before and after AMI. Oxidant parameters were measured in heart tissue and cortisol levels were measured in plasma specimens. Compared with the nonstressed group, stress-exposed rats showed sympathetic hyperactivity characterized by increased HR together with decreased HRV. In the stressed group serum corticosterone levels were high both before and after AMI. Mean infarct size in the stressed group was significantly larger (44.6+/-3.23% and 53.1+/-4.52%, respectively; P<0.05). Increased tissue malondialdehyde (MDA) levels (0.63+/-0.59 and 1.60+/-0.31 nmol/mg protein, respectively; P<0.05) and decreased superoxide dismutase (SOD) activity and glutathione (GSH) content were seen in stress-exposed rats. Likewise, heart peroxynitrite levels were also high in stress-exposed rats (141.8+/-18 nmol/g tissue vs. 164.2+/-21 nmol/g tissue). Chronic emotional stress is a deteriorating factor for the induction and prognosis of MI. Exaggerated sympathetic activity may be the major contributing factor. Oxidative and nitrosative damage in response to this sympathetic hyperactivity is the key mechanism.

  20. Oxidative Stress in Inherited Mitochondrial Diseases

    PubMed Central

    Hayashi, Genki; Cortopassi, Gino

    2015-01-01

    Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially-expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production, or decreased ROS protection. The role of oxidative stresses in the five most common inherited mitochondrial diseases; Friedreich's ataxia (FA), LHON, MELAS, MERRF and Leigh Syndrome (LS) is discussed. Published reports for oxidative stress involvement in pathomechanism in these five mitochondrial diseases are reviewed. The strongest for oxidative stress pathomechanism among the five diseases was in Friedreich's ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for oxidative stress citation count frequency within each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is in Friedreich's ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich's diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich's ataxia. PMID:26073122

  1. Treatment of β-Thalassemia/Hemoglobin E with Antioxidant Cocktails Results in Decreased Oxidative Stress, Increased Hemoglobin Concentration, and Improvement of the Hypercoagulable State

    PubMed Central

    Yanpanitch, Orn-uma; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Fucharoen, Suthat; Siritanaratkul, Noppadol; Kalpravidh, Ruchaneekorn W.

    2015-01-01

    Studies on the antioxidant treatment for thalassemia have reported variable outcomes. However, treatment of thalassemia with a combination of hydrophobic and hydrophilic antioxidants and an iron chelator has not been studied. This study investigated the effects of antioxidant cocktails for the treatment of β-thalassemia/hemoglobin E (HbE), which is the most common form of β-thalassemia in Southeast Asia. Sixty patients were divided into two groups receiving N-acetylcysteine, deferiprone, and either curcuminoids (CUR) or vitamin E (Vit-E), and their hematological parameters, iron load, oxidative stress, and blood coagulation potential were evaluated. Patients were classified as responders if they showed the improvements of the markers of iron load and oxidative stress, otherwise as nonresponders. During treatment, the responders in both groups had significantly decreased iron load, oxidative stress, and coagulation potential and significantly increased antioxidant capacity and hemoglobin concentration. The significantly maximum increase (P < 0.01) in hemoglobin concentration was 11% at month 4 in CUR group responders and 10% at month 10 in Vit-E group responders. In conclusion, the two antioxidant cocktails can improve anemia, iron overload, oxidative stress, and hypercoagulable state in β-thalassemia/HbE. PMID:26078808

  2. Treatment of β-Thalassemia/Hemoglobin E with Antioxidant Cocktails Results in Decreased Oxidative Stress, Increased Hemoglobin Concentration, and Improvement of the Hypercoagulable State.

    PubMed

    Yanpanitch, Orn-uma; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Fucharoen, Suthat; Srichairatanakool, Somdet; Siritanaratkul, Noppadol; Kalpravidh, Ruchaneekorn W

    2015-01-01

    Studies on the antioxidant treatment for thalassemia have reported variable outcomes. However, treatment of thalassemia with a combination of hydrophobic and hydrophilic antioxidants and an iron chelator has not been studied. This study investigated the effects of antioxidant cocktails for the treatment of β-thalassemia/hemoglobin E (HbE), which is the most common form of β-thalassemia in Southeast Asia. Sixty patients were divided into two groups receiving N-acetylcysteine, deferiprone, and either curcuminoids (CUR) or vitamin E (Vit-E), and their hematological parameters, iron load, oxidative stress, and blood coagulation potential were evaluated. Patients were classified as responders if they showed the improvements of the markers of iron load and oxidative stress, otherwise as nonresponders. During treatment, the responders in both groups had significantly decreased iron load, oxidative stress, and coagulation potential and significantly increased antioxidant capacity and hemoglobin concentration. The significantly maximum increase (P < 0.01) in hemoglobin concentration was 11% at month 4 in CUR group responders and 10% at month 10 in Vit-E group responders. In conclusion, the two antioxidant cocktails can improve anemia, iron overload, oxidative stress, and hypercoagulable state in β-thalassemia/HbE.

  3. Increased Oxidative Stress and Inflammation Independent of Body Adiposity in Diabetic and Nondiabetic Controls in falciparum Malaria

    PubMed Central

    Acquah, Samuel; Boampong, Johnson Nyarko; Eghan Jnr, Benjamin Ackon

    2016-01-01

    Information on the extent to which oxidative stress and inflammation occur in the presence of falciparum malaria and type 2 diabetes mellitus in the same individual is limited. This study sought to investigate the extent of inflammation and oxidative stress in adult uncomplicated malaria by measuring fasting levels of lipid peroxides, C-reactive protein (CRP), and total antioxidant power (TAP) before and during falciparum malaria, in 100 respondents with type 2 diabetes and 100 age-matched controls in the Cape Coast metropolis of Ghana. Also, body adiposity index, body mass index, and waist-to-hip ratio were computed. Before and during falciparum malaria, diabetes patients exhibited higher (P < 0.05) levels of CRP and peroxides than controls but TAP and BAI were comparable (P > 0.05) between the two groups. Baseline CRP correlated positively (r = 0.341, P = 0.002) with peroxide only in the diabetic group. During malaria, TAP level in both study groups declined (P < 0.05) by 80% of their baseline levels. CRP correlated negatively (r = −0.352, P = 0.011) with TAP in the control but not the diabetic group. Uncomplicated falciparum malaria elevated inflammation and peroxidation but decreased antioxidant power independent of adiposity. This finding may have implication on cardiovascular health. PMID:27298824

  4. Plant-Adapted Escherichia coli Show Increased Lettuce Colonizing Ability, Resistance to Oxidative Stress and Chemotactic Response

    PubMed Central

    Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Lett, Lina; Curatti, Leonardo

    2014-01-01

    Background Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety. Methods/Principal Findings This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency. Conclusion/Significance These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues. PMID:25313845

  5. Plant-adapted Escherichia coli show increased lettuce colonizing ability, resistance to oxidative stress and chemotactic response.

    PubMed

    Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Lett, Lina; Curatti, Leonardo

    2014-01-01

    Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety. This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency. These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues.

  6. Oxidative stress & male infertility.

    PubMed

    Makker, Kartikeya; Agarwal, Ashok; Sharma, Rakesh

    2009-04-01

    The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumours, a new and important cause has been identified: oxidative stress. Oxidative stress is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body. It is a powerful mechanism that can lead to sperm damage, deformity and eventually, male infertility. This review discusses the physiological need for ROS and their role in normal sperm function. It also highlights the mechanism of production and the pathophysiology of ROS in relation to the male reproductive system and enumerate the benefits of incorporating antioxidants in clinical and experimental settings.

  7. Oxidative Stress in Malaria

    PubMed Central

    Percário, Sandro; Moreira, Danilo R.; Gomes, Bruno A. Q.; Ferreira, Michelli E. S.; Gonçalves, Ana Carolina M.; Laurindo, Paula S. O. C.; Vilhena, Thyago C.; Dolabela, Maria F.; Green, Michael D.

    2012-01-01

    Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy. PMID:23208374

  8. Impact of oxidative stress in fetal programming.

    PubMed

    Thompson, Loren P; Al-Hasan, Yazan

    2012-01-01

    Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

  9. CVD and Oxidative Stress

    PubMed Central

    Cervantes Gracia, Karla; Llanas-Cornejo, Daniel; Husi, Holger

    2017-01-01

    Nowadays, it is known that oxidative stress plays at least two roles within the cell, the generation of cellular damage and the involvement in several signaling pathways in its balanced normal state. So far, a substantial amount of time and effort has been expended in the search for a clear link between cardiovascular disease (CVD) and the effects of oxidative stress. Here, we present an overview of the different sources and types of reactive oxygen species in CVD, highlight the relationship between CVD and oxidative stress and discuss the most prominent molecules that play an important role in CVD pathophysiology. Details are given regarding common pharmacological treatments used for cardiovascular distress and how some of them are acting upon ROS-related pathways and molecules. Novel therapies, recently proposed ROS biomarkers, as well as future challenges in the field are addressed. It is apparent that the search for a better understanding of how ROS are contributing to the pathophysiology of CVD is far from over, and new approaches and more suitable biomarkers are needed for the latter to be accomplished. PMID:28230726

  10. The impact of organic farming on quality of tomatoes is associated to increased oxidative stress during fruit development.

    PubMed

    Oliveira, Aurelice B; Moura, Carlos F H; Gomes-Filho, Enéas; Marco, Claudia A; Urban, Laurent; Miranda, Maria Raquel A

    2013-01-01

    This study was conducted with the objective of testing the hypothesis that tomato fruits from organic farming accumulate more nutritional compounds, such as phenolics and vitamin C as a consequence of the stressing conditions associated with farming system. Growth was reduced in fruits from organic farming while titratable acidity, the soluble solids content and the concentrations in vitamin C were respectively +29%, +57% and +55% higher at the stage of commercial maturity. At that time, the total phenolic content was +139% higher than in the fruits from conventional farming which seems consistent with the more than two times higher activity of phenylalanine ammonia lyase (PAL) we observed throughout fruit development in fruits from organic farming. Cell membrane lipid peroxidation (LPO) degree was 60% higher in organic tomatoes. SOD activity was also dramatically higher in the fruits from organic farming. Taken together, our observations suggest that tomato fruits from organic farming experienced stressing conditions that resulted in oxidative stress and the accumulation of higher concentrations of soluble solids as sugars and other compounds contributing to fruit nutritional quality such as vitamin C and phenolic compounds.

  11. The Impact of Organic Farming on Quality of Tomatoes Is Associated to Increased Oxidative Stress during Fruit Development

    PubMed Central

    Oliveira, Aurelice B.; Moura, Carlos F. H.; Gomes-Filho, Enéas; Marco, Claudia A.; Urban, Laurent; Miranda, Maria Raquel A.

    2013-01-01

    This study was conducted with the objective of testing the hypothesis that tomato fruits from organic farming accumulate more nutritional compounds, such as phenolics and vitamin C as a consequence of the stressing conditions associated with farming system. Growth was reduced in fruits from organic farming while titratable acidity, the soluble solids content and the concentrations in vitamin C were respectively +29%, +57% and +55% higher at the stage of commercial maturity. At that time, the total phenolic content was +139% higher than in the fruits from conventional farming which seems consistent with the more than two times higher activity of phenylalanine ammonia lyase (PAL) we observed throughout fruit development in fruits from organic farming. Cell membrane lipid peroxidation (LPO) degree was 60% higher in organic tomatoes. SOD activity was also dramatically higher in the fruits from organic farming. Taken together, our observations suggest that tomato fruits from organic farming experienced stressing conditions that resulted in oxidative stress and the accumulation of higher concentrations of soluble solids as sugars and other compounds contributing to fruit nutritional quality such as vitamin C and phenolic compounds. PMID:23437115

  12. Associating growth-phase-related changes in the proteome of Acinetobacter baumannii with increased resistance to oxidative stress.

    PubMed

    Soares, Nelson C; Cabral, Maria P; Gayoso, Carmen; Mallo, Susana; Rodriguez-Velo, Patricia; Fernández-Moreira, Esteban; Bou, Germán

    2010-04-05

    Acinetobacter baumannii is an opportunistic pathogen that has been associated with severe infections and outbreaks in hospitals. At present, very little is known about the biology of this bacterium, particularly as regards mechanisms of adaptation, persistence and virulence. To investigate the growth phase-dependent regulation of proteins in this microorganism, we analyzed the proteomic pattern of A. baumannii ATCC 17978 at different stages of in vitro growth. In this study, proteomics analyses were conducted using 2-DE and MALDI-TOF/TOF complemented by iTRAQ LC-MS/MS. Here we have identified 107 differentially expressed proteins. We highlight the induction of proteins associated with signaling, putative virulence factors and response to stress (including oxidative stress). We also present evidence that ROS (O(2)(-) and OH(-)) and RNI (ONOO(-)) accumulate during late stages of growth. Further assays demonstrated that stationary cells survive at high concentrations of H(2)O(2) (30 mM), the O(2)(-) donor menadione (500 muM) or the NO donor sodium nitroprusside (1 mM), and showed a higher survival rate against several bactericidal antibiotics. The growth phase-dependent changes observed in the A. baumannii proteome are discussed within a context of adaptive biological responses, including those related to ROS and RNI stress.

  13. Increased oxidative stress and cytotoxicity by hydrogen sulfide in HepG2 cells overexpressing cytochrome P450 2E1.

    PubMed

    Caro, Andres A; Thompson, Sarah; Tackett, Jonathan

    2011-12-01

    The main objectives of this work were to evaluate the effects of hydrogen sulfide on oxidative stress and cytotoxicity parameters in HepG2 cells and to assess the extent to which cytochrome P450 2E1 (CYP2E1) activity modulates the effects of hydrogen sulfide on oxidative stress and cytotoxicity. Sodium hydrosulfide (NaHS) caused time- and concentration-dependent cytotoxicity in both non-P450-expressing HepG2 cells (C34 cells) and CYP2E1-overexpressing HepG2 cells (E47 cells); however, NaHS-dependent cytotoxicity was higher in E47 than C34 cells. Cytotoxicity by NaHS in C34 and E47 cells was mainly necrotic in nature and associated with an early decrease in mitochondrial membrane potential. NaHS caused increased oxidation of lipophilic (C11-BODIPY(581/591)) and hydrophilic (DCFH-DA) probes only in E47 cells, at a time point prior to overt cytotoxicity. Trolox, an amphipathic antioxidant, partially inhibited both the cytotoxicity and the increased oxidative stress detected in E47 cells exposed to NaHS. Cell-permeable iron chelators and CYP2E1 inhibitors significantly inhibited the oxidation of C11-BODIPY(581/591) in E47 cells in the presence of NaHS. NaHS produced lipid peroxidation and cytotoxicity in E47 cells supplemented with a representative polyunsaturated fatty acid (docosahexaenoic acid) but not in C34 cells; these effects were inhibited by α-tocopherol, a lipophilic antioxidant. These data suggest that CYP2E1 enhances H(2)S-dependent cytotoxicity in HepG2 cells through the generation of iron-dependent oxidative stress and lipid peroxidation.

  14. Increased oxidative stress and cytotoxicity by hydrogen sulfide in HepG2 cells overexpressing cytochrome P450 2E1

    PubMed Central

    Caro, Andres A.; Thompson, Sarah; Tackett, Jonathan

    2013-01-01

    The main objectives of this work were to evaluate the effects of hydrogen sulfide on oxidative stress and cytotoxicity parameters in HepG2 cells and to assess the extent to which cytochrome P450 2E1 (CYP2E1) activity modulates the effects of hydrogen sulfide on oxidative stress and cytotoxicity. Sodium hydrosulfide (NaHS) caused time- and concentration-dependent cytotoxicity in both non-P450-expressing HepG2 cells (C34 cells) and CYP2E1-overexpressing HepG2 cells (E47 cells); however, NaHS-dependent cytotoxicity was higher in E47 than C34 cells. Cytotoxicity by NaHS in C34 and E47 cells was mainly necrotic in nature and associated with an early decrease in mitochondrial membrane potential. NaHS caused increased oxidation of lipophilic (C11-BODIPY581/591) and hydrophilic (DCFH-DA) probes only in E47 cells, at a time point prior to overt cytotoxicity. Trolox, an amphipathic antioxidant, partially inhibited both the cytotoxicity and the increased oxidative stress detected in E47 cells exposed to NaHS. Cell-permeable iron chelators and CYP2E1 inhibitors significantly inhibited the oxidation of C11-BODIPY581/591 in E47 cells in the presence of NaHS. NaHS produced lipid peroxidation and cytotoxicity in E47 cells supplemented with a representative polyunsaturated fatty acid (docosahexaenoic acid) but not in C34 cells; these effects were inhibited by α-tocopherol, a lipophilic antioxidant. These data suggest that CYP2E1 enhances H2S-dependent cytotoxicity in HepG2 cells through the generation of iron-dependent oxidative stress and lipid peroxidation. PMID:21850523

  15. Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus.

    PubMed

    Labinskyy, Nazar; Mukhopadhyay, Partha; Toth, Janos; Szalai, Gabor; Veres, Monika; Losonczy, Gyorgy; Pinto, John T; Pacher, Pal; Ballabh, Praveen; Podlutsky, Andrej; Austad, Steven N; Csiszar, Anna; Ungvari, Zoltan

    2009-04-01

    Vascular aging is characterized by increased oxidative stress and proinflammatory phenotypic alterations. Metabolic stress, such as hyperglycemia in diabetes, is known to increase the production of ROS and promote inflammatory gene expression, accelerating vascular aging. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower steady-state production of ROS and/or superior resistance to the prooxidant effects of metabolic stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr, respectively). We compared interspecies differences in steady-state and high glucose (HG; 30 mmol/l)-induced production of O(2)(*-) and H(2)O(2), endothelial function, mitochondrial ROS generation, and inflammatory gene expression in cultured aortic segments. In P. leucopus aortas, steady-state endothelial O(2)(*-) and H(2)O(2) production and ROS generation by mitochondria were less than in M. musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited less steady-state and HG-induced ROS production than M. musculus cells. In M. musculus arteries, HG elicited significant upregulation of inflammatory markers (TNF-alpha, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In contrast, the proinflammatory effects of HG were blunted in P. leucopus vessels. Thus, increased life span potential in P. leucopus is associated with decreased cellular ROS generation and increased resistance to prooxidant and proinflammatory effects of metabolic stress, which accord with predictions of the oxidative stress hypothesis of aging.

  16. Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus

    PubMed Central

    Labinskyy, Nazar; Mukhopadhyay, Partha; Toth, Janos; Szalai, Gabor; Veres, Monika; Losonczy, Gyorgy; Pinto, John T.; Pacher, Pal; Ballabh, Praveen; Podlutsky, Andrej; Austad, Steven N.; Csiszar, Anna; Ungvari, Zoltan

    2009-01-01

    Vascular aging is characterized by increased oxidative stress and proinflammatory phenotypic alterations. Metabolic stress, such as hyperglycemia in diabetes, is known to increase the production of ROS and promote inflammatory gene expression, accelerating vascular aging. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower steady-state production of ROS and/or superior resistance to the prooxidant effects of metabolic stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr, respectively). We compared interspecies differences in steady-state and high glucose (HG; 30 mmol/l)-induced production of O2•− and H2O2, endothelial function, mitochondrial ROS generation, and inflammatory gene expression in cultured aortic segments. In P. leucopus aortas, steady-state endothelial O2•− and H2O2 production and ROS generation by mitochondria were less than in M. musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited less steady-state and HG-induced ROS production than M. musculus cells. In M. musculus arteries, HG elicited significant upregulation of inflammatory markers (TNF-α, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In contrast, the proinflammatory effects of HG were blunted in P. leucopus vessels. Thus, increased life span potential in P. leucopus is associated with decreased cellular ROS generation and increased resistance to prooxidant and proinflammatory effects of metabolic stress, which accord with predictions of the oxidative stress hypothesis of aging. PMID:19181967

  17. Nrf2 expression is increased in peripheral blood mononuclear cells derived from mild-moderate ex-smoker COPD patients with persistent oxidative stress.

    PubMed

    Fratta Pasini, Anna Maria; Ferrari, Marcello; Stranieri, Chiara; Vallerio, Paola; Mozzini, Chiara; Garbin, Ulisse; Zambon, Giorgia; Cominacini, Luciano

    2016-01-01

    Inadequacy of antioxidant nuclear factor-E2-related factor 2 (Nrf2) and endoplasmic reticulum stress-mediated unfolded protein response has been implicated in severe chronic obstructive pulmonary disease (COPD) and cigarette smoking-induced emphysema. As evidence suggests that the ability to upregulate Nrf2 expression may influence the progression of COPD and no data exist up to now in ex-smokers with mild-moderate COPD, this study was first aimed to evaluate Nrf2 and unfolded protein response expression in peripheral blood mononuclear cells (PBMC) of mild-moderate ex-smokers with COPD compared to smoking habit-matched non-COPD subjects. Then, we tested whether oxidative stress persists after cigarette smoking cessation and whether the concentrations of oxidized phospholipids (oxidation products of the phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine [oxPAPC]) in the PBMC of the same subjects may have a causative role in determining the upregulation of Nrf2. The expression (mRNA and protein) of Nrf2 and of its related gene heme oxygenase-1 was significantly increased in COPD group without differences in the unfolded protein response. Plasma malondialdehyde, the circulating marker of oxidative stress, and oxPAPC in PBMC were significantly higher in COPD than in non-COPD subjects. The fact that the expression of p47phox, a subunit of NADPH oxidase, was increased in PBMC of COPD patients and that it was directly correlated with oxPAPC may indicate that oxPAPC may be one of the determinants of oxidative stress-induced Nrf2 upregulation. Finally, we also demonstrated that lung function inversely correlated with plasma malondialdehyde and with Nrf2 and heme oxygenase-1 mRNA expression in all subjects. Our results indicate that mild-moderate ex-smokers with COPD may be able to counteract oxidative stress by increasing the expression of Nrf2/antioxidant-response elements. Because Nrf2 failure significantly contributes to the development of COPD, our

  18. Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke.

    PubMed

    Al-Attas, Omar S; Hussain, Tajamul; Ahmed, Mukhtar; Al-Daghri, Nasser; Mohammed, Arif A; De Rosas, Edgard; Gambhir, Dikshit; Sumague, Terrance S

    2015-07-01

    Incense smoke exposure has recently been linked to cardiovascular disease risk, heart rate variability, and endothelial dysfunction. To test the possible underlying mechanisms, oxidative stress, and inflammatory markers, gene expressions of cardiac hypertrophic and xenobiotic-metabolizing enzymes and ultrastructural changes were measured, respectively, using standard, ELISA-based, real-time PCR, and transmission electron microscope procedures in heart tissues of Wistar rats after chronically exposing to Arabian incense. Malondialdehyde, tumor necrosis alpha (TNF)-α, and IL-4 levels were significantly increased, while catalase and glutathione levels were significantly declined in incense smoke-exposed rats. Incense smoke exposure also resulted in a significant increase in atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain, CYP1A1 and CYP1A2 messenger RNAs (mRNAs). Rats exposed to incense smoke displayed marked ultrastructural changes in heart muscle with distinct cardiac hypertrophy, which correlated with the augmented hypertrophic gene expression as well as markers of cardiac damage including creatine kinase-myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Increased oxidative stress, inflammation, altered cardiac hypertrophic gene expression, tissue damage, and architectural changes in the heart may collectively contribute to increased cardiovascular disease risk in individuals exposed to incense smoke. Increased gene expressions of CYP1A1 and CYP1A2 may be instrumental in the incense smoke-induced oxidative stress and inflammation. Thus, incense smoke can be considered as a potential environmental pollutant and its long-term exposure may negatively impact human health.

  19. Direct effect of chronic hypoxia in suppressing large conductance Ca(2+)-activated K(+) channel activity in ovine uterine arteries via increasing oxidative stress.

    PubMed

    Hu, Xiang-Qun; Huang, Xiaohui; Xiao, Daliao; Zhang, Lubo

    2016-01-15

    Chronic hypoxia has a direct effect in down-regulating the BKCa channel β1 subunit and inhibiting the BKCa channel activity in uterine arteries of pregnant sheep. Oxidative stress plays a causal role in hypoxia-mediated suppression of BKCa channel function. The steroid hormone-induced effect on BKCa channels is a target of hypoxia-mediated oxidative stress. Inhibition of oxidative stress ameliorates the adverse effect of hypoxia both ex vivo and in vivo in pregnant sheep exposed to long-term high-altitude hypoxia. Our findings provide novel evidence of a causative role of oxidative stress in hypoxia-mediated inhibition of the BKCa channel activity in uterine arteries and new insights in understanding and alleviating pregnancy complications associated with gestational hypoxia such as pre-eclampsia and fetal growth restriction. Uterine arteries of pregnant sheep acclimatized to long-term high-altitude hypoxia were associated with a decrease in large-conductance Ca(2+)-activated K(+) (BKCa) channel activity. The present study tested the hypothesis that prolonged hypoxia has a direct effect in suppressing BKCa channel activity by increasing oxidative stress. Uterine arteries were isolated from non-pregnant and near-term (∼142 days) pregnant sheep, and were treated ex vivo with 21.0 or 10.5% O2 for 48 h. The hypoxia treatment significantly increased the production of reactive oxygen species in uterine arteries, which was blocked by N-acetylcysteine. In uterine arteries of pregnant sheep, hypoxia significantly inhibited BKCa channel current density, decreased NS1619-induced relaxations and increased pressure-dependent tone, which were annulled by N-acetylcysteine. In accordance, hypoxia resulted in down-regulation of BKCa channel β1 subunit, which was restored in the presence of N-acetylcysteine. In addition, the N-acetylcysteine treatment significantly increased BKCa channel β1 subunit abundance and BKCa channel current density in uterine arteries from pregnant

  20. Estradiol and neurodegenerative oxidative stress.

    PubMed

    Nilsen, Jon

    2008-10-01

    Estradiol is a potent preventative against neurodegenerative disease, in part, by activating antioxidant defense systems scavenging reactive oxygen species, limiting mitochondrial protein damage, improving electron transport chain activity and reducing mitochondrial DNA damage. Estradiol also increases the activity of complex IV of the electron transport chain, improving mitochondrial respiration and ATP production under normal and stressful conditions. However, the high oxidative cellular environment present during neurodegeneration makes estradiol a poor agent for treatment of existing disease. Oxidative stress stimulates the production of the hydroperoxide-dependent hydroxylation of estradiol to the catecholestrogen metabolites, which can undergo reactive oxygen species producing redox cycling, setting up a self-generating toxic cascade offsetting any antioxidant/antiapoptotic effects generated by the parent estradiol. Additional disease-induced factors can further perpetuate this cycle. For example dysregulation of the catecholamine system could alter catechol-O-methyltransferase-catalyzed methylation, preventing removal of redox cycling catecholestrogens from the system enhancing pro-oxidant effects of estradiol.

  1. High glucose and ketosis (acetoacetate) increases, and chromium niacinate decreases, IL-6, IL-8, and MCP-1 secretion and oxidative stress in U937 monocytes.

    PubMed

    Jain, Sushil K; Rains, Justin L; Croad, Jennifer L

    2007-10-01

    Elevated blood levels of the proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and MCP-1 (monocyte chemoattractant protein-1) increase insulin resistance and the risk of cardiovascular disease (CVD). There is no previous study that has examined the effect of ketosis and trivalent chromium on IL-6, IL-8, or MCP-1 secretion in any cell type or in human or animal model. The authors examined the hypothesis that ketosis increases and trivalent chromium decreases the levels of cytokines and oxidative stress in diabetes using a U937 monocyte cell culture model. Cells were cultured with control, high glucose (HG), and acetoacetate (AA) in the absence or presence (0.5-10 microM) of CrCl(3), chromium picolinate (Cr-P), or chromium niacinate (Cr-N) at 37 degrees C for 24 h. The data show a significant stimulation of IL-6, IL-8, and MCP-1 secretion and an increase in oxidative stress in cells treated with HG or AA. The effect of HG on cytokine secretion was reduced by Cr-N, and to a lesser extent by CrCl(3) and Cr-P. The effect of HG on oxidative stress was reduced by Cr-N and CrCl 3, but not by Cr-P. Similarly, Cr-N decreased the cytokine secretion in HG + AA-treated cells. Cr-N significantly decreased standard oxidant (H(2)O(2)) induced cytokine secretion, which suggests that reduction of cytokine secretion by Cr-N is in part mediated by its antioxidative effect. In a cell culture model, Cr-N appears to be the most effective form of chromium in inhibiting oxidative stress and proinflammatory cytokine secretion by monocytes. This study suggests that chromium niacinate supplementation may be useful in reducing vascular inflammation and the risk of CVD in diabetes.

  2. Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats.

    PubMed

    Asghar, Mohammad; Monjok, Emmanuel; Kouamou, Ghislaine; Ohia, Sunny E; Bagchi, Debasis; Lokhandwala, Mustafa F

    2007-10-01

    Super CitriMax (HCA-SX) is a novel calcium/potassium salt of (-)-hydroxycitric acid extracted from the dried fruit rind of the plant Garcinia cambogia, and commonly consumed as weight loss dietary supplement. In the present study, we investigated the effect of HCA-SX on inflammation, oxidative stress and insulin resistance in developing obese Zucker rats, an animal model of type II diabetes associated with inflammation and oxidative stress. Male Zucker rats (5-week old) were supplemented with vehicle (control) and HCA-SX in drinking water for 7 weeks. Oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (DNPH), and protein tyrosine nitration (tyr-NO(2)) were measured in the liver and kidney tissues using biochemical and immunoblotting techniques. Compared to controls, the levels of MDA, DNPH and tyr-NO(2) were lower in the liver and kidney of HCA-SX-treated animals. Furthermore, the levels of C-reactive protein and interleukin-6, markers of inflammation measured by ELISA, were lower in the plasma of HCA-SX-supplemented animals compared to controls, as were levels of fasting plasma insulin, glucose, and triglycerides. Interestingly, insulin resistance did not develop in HCA-SX-supplemented rats. Food-intake and body weight gain was also lower in rats supplemented with HCA-SX compared to their control counterparts. These results suggest that HCA-SX supplementation in obese Zucker rats reduces food-intake, body weight gain, and also attenuates the increases in inflammation, oxidative stress, and insulin resistance observed in untreated animals. Therefore, HCA-SX may be used as an intervention to overcome obesity-related complications, including inflammation, oxidative stress, and insulin resistance.

  3. [Lactose-induced diarrhea increases oxidative stress and it is more severe in rats deficient in vitamin E].

    PubMed

    Dellán, Graciela; Carías, Diamela; Cioccia, Anna M; González, Eduardo; Hevia, Patricio

    2005-03-01

    Diarrhea is the disease with high incidence in the world and causes infant mortality and malnutrition in the developing world. This justifies the study of nutrition and diarrhea. Due to ethical and financial considerations it is difficult to study nutrition and diarrhea in children thus animal models have become a convenient alternative. In previous studies it was shown that lactose induced diarrhea in rats was associated with a reduction in tissue levels of vitamin E and also with evidence of an inflammatory response of the intestine. Accordingly, in this study, in order to determine the effect of this type of diarrhea on the level of oxidative stress, diarrhea was induced in vitamin E sufficient and deficient rats. The results showed that after 23 days the tissue concentration of vitamin E decreased in all the rats with diarrhea but this reduction was substantially greater in the vitamin E deficient group. Moreover, diarrhea was 60% more severe in the vitamin E deficient rats than in the vitamin E sufficient group that also had diarrhea. Both diarrhea and vitamin E deficiency altered malonaldehyde and superoxide dismutase levels in various tissues. However, the most outstanding changes associated with diarrhea were a 100% increment in plasma malonaldehyde and erythrocyte superoxide dismutase activities which were 8 to 11 times higher than those seen in the rats without diarrhea. These non-invasive changes correlated well with the severity of diarrhea. The study shows that vitamin E deficiency results in diarrheas which are more severe and that lactose induced diarrhea is associated with higher levels of oxidative stress.

  4. Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: implications for neurodegeneration in Alzheimer's disease.

    PubMed

    Venkateshappa, C; Harish, G; Mahadevan, Anita; Srinivas Bharath, M M; Shankar, S K

    2012-08-01

    Oxidative stress and mitochondrial damage are implicated in the evolution of neurodegenerative diseases. Increased oxidative damage in specific brain regions during aging might render the brain susceptible to degeneration. Previously, we demonstrated increased oxidative damage and lowered antioxidant function in substantia nigra during aging making it vulnerable to degeneration associated with Parkinson's disease. To understand whether aging contributes to the vulnerability of brain regions in Alzheimer's disease, we assessed the oxidant and antioxidant markers, glutathione (GSH) metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I (CI) activity in hippocampus (HC) and frontal cortex (FC) compared with cerebellum (CB) in human brains with increasing age (0.01-80 years). We observed significant increase in protein oxidation (HC: p = 0.01; FC: p = 0.0002) and protein nitration (HC: p = 0.001; FC: p = 0.02) and increased GFAP expression (HC: p = 0.03; FC: p = 0.001) with a decreasing trend in CI activity in HC and FC compared to CB with increasing age. These changes were associated with a decrease in antioxidant enzyme activities, such as superoxide dismutase (HC: p = 0.005), catalase (HC: p = 0.02), thioredoxin reductase (FC: p = 0.04), GSH reductase (GR) (HC: p = 0.005), glutathione-s-transferase (HC: p = 0.0001; FC: p = 0.03) and GSH (HC: p = 0.01) with age. However, these parameters were relatively unaltered in CB. We suggest that the regions HC and FC are subjected to widespread oxidative stress, loss of antioxidant function and enhanced GFAP expression during aging which might make them more susceptible to deranged physiology and selective neuronal degeneration.

  5. Oxidative stress and hypertension.

    PubMed

    Harrison, David G; Gongora, Maria Carolina

    2009-05-01

    This review has summarized some of the data supporting a role of ROS and oxidant stress in the genesis of hypertension. There is evidence that hypertensive stimuli, such as high salt and angiotensin II, promote the production of ROS in the brain, the kidney, and the vasculature and that each of these sites contributes either to hypertension or to the untoward sequelae of this disease. Although the NADPH oxidase in these various organs is a predominant source, other enzymes likely contribute to ROS production and signaling in these tissues. A major clinical challenge is that the routinely used antioxidants are ineffective in preventing or treating cardiovascular disease and hypertension. This is likely because these drugs are either ineffective or act in a non-targeted fashion, such that they remove not only injurious ROS Fig. 5. Proposed role of T cells in the genesis of hypertension and the role of the NADPH oxidase in multiple cells/organs in modulating this effect. In this scenario, angiotensin II stimulates an NADPH oxidase in the CVOs of the brain, increasing sympathetic outflow. Sympathetic nerve terminals in lymph nodes activate T cells, and angiotensin II also directly activates T cells. These stimuli also activate expression of homing signals in the vessel and likely the kidney, which attract T cells to these organs. T cells release cytokines that stimulate the vessel and kidney NADPH oxidases, promoting vasoconstriction and sodium retention. SFO, subfornical organ. 630 Harrison & Gongora but also those involved in normal cell signaling. A potentially important and relatively new direction is the concept that inflammatory cells such as T cells contribute to hypertension. Future studies are needed to understand the interaction of T cells with the CNS, the kidney, and the vasculature and how this might be interrupted to provide therapeutic benefit.

  6. Immune dysfunction and increased oxidative stress state in diet-induced obese mice are reverted by nutritional supplementation with monounsaturated and n-3 polyunsaturated fatty acids.

    PubMed

    Hunsche, Caroline; Hernandez, Oskarina; Gheorghe, Alina; Díaz, Ligia Esperanza; Marcos, Ascensión; De la Fuente, Mónica

    2017-02-23

    Obesity is associated with impaired immune defences and chronic low levels of inflammation and oxidation. In addition, this condition may lead to premature aging. The aim of the study was to evaluate the effects of a nutritional supplementation with monounsaturated and n-3 polyunsaturated fatty acids on several functions and oxidative stress parameters in peritoneal immune cells of obese mice, as well as on the life span of these animals. Obesity was induced in adult female ICR/CD1 by the administration of a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of obese mice received the same HFD, supplemented with 1500 mg of 2-hydroxyoleic acid (2-OHOA) and another with 3000 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Several functions and oxidative stress parameters of peritoneal leukocytes were evaluated. The groups of obese mice treated with 2-OHOA or with EPA and DHA showed a significant improvement in several functions such as chemotaxis, phagocytosis, digestion capacity, Natural killer activity and lymphoproliferation in response to mitogens. All of these functions, which were decreased in obese mice, increased reaching similar levels to those found in non-obese controls. Both treatments also improved oxidative stress parameters such as xanthine oxidase activity, which decreased, catalase activity and glutathione levels, which increased. These data suggest that dietary supplementation with monounsaturated and n-3 polyunsaturated fatty acids could be an effective nutritional intervention to restore the immune response and oxidative stress state, which are impaired in obese mice.

  7. Hemoglobin oxidative stress in cancer.

    PubMed

    Della Rovere, F; Granata, A; Broccio, M; Zirilli, A; Broccio, G

    1995-01-01

    The role played by free radicals in carcinogenesis and their relationships with antioxidant pool and cancer have already been shown. Free radicals induce increased membrane permeability through membrane lipid peroxidation, protein oxidation and histamine release from mast cells. Free radicals also cause oxyhemoglobin oxidative stress which increases methemoglobin and hemichromes. For this reason, we studied the in vitro formation of methemoglobin at 0' and 90', dosed following the HPLC method, after oxidative stress of blood by means of acetylphenylhydrazine in 40 subjects with cancer and 40 healthy donors. The results showed that methemoglobin formation was highly significant in tumors as compared to controls (P < 0.0001). The statistical analyses we carried out showed that metHb formation is not affected by age, sex, smoking habit, red blood cell number, Hb, Ht or tumor staging. This makes us believe that free radicals alter erythrocyte membrane permeability and predenaturate oxyhemoglobin so that erythrocyte membrane becomes more susceptible to new oxidative stress. This caused the abnormal response we found. Our results clearly underline the role played by free radicals in tumorous disease and provide a successful and easy method to detect early, even in a pre-clinical stage, the presence of tumorous alterations in the human body.

  8. Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts.

    PubMed

    Zhang, Yu; Yang, Jian-Hong

    2013-11-01

    Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt-related transcription factor 2 (Runx2), collagen I, and osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator-activated receptor gamma, adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, high glucose-induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY-294002, reversed the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose-induced increase of adipogenic differentiation, which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence, suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia.

  9. Mitochondrial and peroxisomal fatty acid oxidation capacities increase in the skeletal muscles of young pigs during early postnatal development but are not affected by cold stress.

    PubMed

    Herpin, Patrick; Vincent, Annie; Fillaut, Martine; Bonito, Bruno Piteira; Hocquette, Jean-François

    2003-01-01

    In pigs, the optimal utilization of energy substrates within muscle fibers is a prerequisite of the utmost importance for successful adaptation to extra-uterine life. In the present work we demonstrate that fatty acid (FA) oxidative capacities increased within the first five days of life in piglet skeletal muscle. Mitochondrial FA oxidation capacities increased more in the rhomboideus oxidative than in the longissimus lumborum glycolytic muscle (+114% vs. +62%, P < 0.001). The apparent rate of fatty acid degradation by peroxisomes represents 30 to 40% of total FA oxidation capacities and increased by about 170% (P < 0.001) with age in both muscles. The postnatal enhancement of skeletal muscle oxidative capacities was further supported by a rise in acid-soluble and long-chain acylcamitine tissue levels (+67%, P < 0.01), and plasma levels of albumin (+160%, P < 0.001). Cold stress had no effect on mitochondrial and peroxisomal FA oxidation but greatly enhanced (+61%, P < 0.05) the circulating levels of non-esterified fatty acids at five days of life.

  10. Expression of the tetrahydrofolate-dependent nitric oxide synthase from the green alga Ostreococcus tauri increases tolerance to abiotic stresses and influences stomatal development in Arabidopsis.

    PubMed

    Foresi, Noelia; Mayta, Martín L; Lodeyro, Anabella F; Scuffi, Denise; Correa-Aragunde, Natalia; García-Mata, Carlos; Casalongué, Claudia; Carrillo, Néstor; Lamattina, Lorenzo

    2015-06-01

    Nitric oxide (NO) is a signaling molecule with diverse biological functions in plants. NO plays a crucial role in growth and development, from germination to senescence, and is also involved in plant responses to biotic and abiotic stresses. In animals, NO is synthesized by well-described nitric oxide synthase (NOS) enzymes. NOS activity has also been detected in higher plants, but no gene encoding an NOS protein, or the enzymes required for synthesis of tetrahydrobiopterin, an essential cofactor of mammalian NOS activity, have been identified so far. Recently, an NOS gene from the unicellular marine alga Ostreococcus tauri (OtNOS) has been discovered and characterized. Arabidopsis thaliana plants were transformed with OtNOS under the control of the inducible short promoter fragment (SPF) of the sunflower (Helianthus annuus) Hahb-4 gene, which responds to abiotic stresses and abscisic acid. Transgenic plants expressing OtNOS accumulated higher NO concentrations compared with siblings transformed with the empty vector, and displayed enhanced salt, drought and oxidative stress tolerance. Moreover, transgenic OtNOS lines exhibited increased stomatal development compared with plants transformed with the empty vector. Both in vitro and in vivo experiments indicate that OtNOS, unlike mammalian NOS, efficiently uses tetrahydrofolate as a cofactor in Arabidopsis plants. The modulation of NO production to alleviate abiotic stress disturbances in higher plants highlights the potential of genetic manipulation to influence NO metabolism as a tool to improve plant fitness under adverse growth conditions.

  11. Differentiation-Associated Downregulation of Poly(ADP-Ribose) Polymerase-1 Expression in Myoblasts Serves to Increase Their Resistance to Oxidative Stress.

    PubMed

    Oláh, Gábor; Szczesny, Bartosz; Brunyánszki, Attila; López-García, Isabel A; Gerö, Domokos; Radák, Zsolt; Szabo, Csaba

    2015-01-01

    Poly(ADP-ribose) polymerase 1 (PARP-1), the major isoform of the poly (ADP-ribose) polymerase family, is a constitutive nuclear and mitochondrial protein with well-recognized roles in various essential cellular functions such as DNA repair, signal transduction, apoptosis, as well as in a variety of pathophysiological conditions including sepsis, diabetes and cancer. Activation of PARP-1 in response to oxidative stress catalyzes the covalent attachment of the poly (ADP-ribose) (PAR) groups on itself and other acceptor proteins, utilizing NAD+ as a substrate. Overactivation of PARP-1 depletes intracellular NAD+ influencing mitochondrial electron transport, cellular ATP generation and, if persistent, can result in necrotic cell death. Due to their high metabolic activity, skeletal muscle cells are particularly exposed to constant oxidative stress insults. In this study, we investigated the role of PARP-1 in a well-defined model of murine skeletal muscle differentiation (C2C12) and compare the responses to oxidative stress of undifferentiated myoblasts and differentiated myotubes. We observed a marked reduction of PARP-1 expression as myoblasts differentiated into myotubes. This alteration correlated with an increased resistance to oxidative stress of the myotubes, as measured by MTT and LDH assays. Mitochondrial function, assessed by measuring mitochondrial membrane potential, was preserved under oxidative stress in myotubes compared to myoblasts. Moreover, basal respiration, ATP synthesis, and the maximal respiratory capacity of mitochondria were higher in myotubes than in myoblasts. Inhibition of the catalytic activity of PARP-1 by PJ34 (a phenanthridinone PARP inhibitor) exerted greater protective effects in undifferentiated myoblasts than in differentiated myotubes. The above observations in C2C12 cells were also confirmed in a rat-derived skeletal muscle cell line (L6). Forced overexpression of PARP1 in C2C12 myotubes sensitized the cells to oxidant

  12. HMG-CoA reductase inhibitors prevent migration of human coronary smooth muscle cells through suppression of increase in oxidative stress.

    PubMed

    Yasunari, K; Maeda, K; Minami, M; Yoshikawa, J

    2001-06-01

    In vitro and in vivo evidence of a decrease in vascular smooth muscle cell (SMC) migration induced by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has been reported. When added to SMC cultures for 6 hours, the HMG-CoA reductase inhibitors fluvastatin, simvastatin, and pravastatin at 1 micromol/L resulted in a 48%, 50%, and 16% suppression, respectively, of human coronary SMC migration; these reductions mirrored the suppression in oxidative stress induced by 1 micromol/L lysophosphatidylcholine (lyso-PC) of 50%, 53% and 19%, respectively. The hydroxylated metabolites of fluvastatin, M(2) and M(3), at 1 micromol/L also suppressed the enhancement of SMC migration by 58% and 45% and the increase in oxidative stress induced by lyso-PC of 58% and 49%, respectively. Lyso-PC activated phospholipase D and protein kinase C (PKC), and this activation was also suppressed by HMG-CoA reductase inhibitors. The inhibition of phospholipase D and PKC was reversed by 100 micromol/L mevalonate, its isoprenoid derivative, farnesol, and geranylgeraniol but not by 10 micromol/L squalene. Antisense oligodeoxynucleotides at 5 micromol/L to PKC-alpha, but not those to the PKC-beta isoform, suppressed the lyso-PC-mediated increases in SMC migration and oxidative stress. These findings suggest that HMG-CoA reductase inhibitors have direct antimigratory effects on the vascular wall beyond their effects on plasma lipids and that they might exert such antimigratory effects via suppression of the phospholipase D- and PKC (possibly PKC-alpha)-induced increase in oxidative stress, which might in turn prevent significant coronary artery disease.

  13. Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect.

    PubMed

    Picone, Pasquale; Nuzzo, Domenico; Caruana, Luca; Messina, Elisa; Barera, Annalisa; Vasto, Sonya; Di Carlo, Marta

    2015-05-01

    Clinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformin's effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy.

    PubMed

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen; Chen, Gang

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.

  15. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    PubMed Central

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  16. Oxidative stress and increased formation of vasoconstricting F2-isoprostanes in patients with reversible cerebral vasoconstriction syndrome.

    PubMed

    Chen, Shih-Pin; Chung, Yu-Ting; Liu, Tsung-Yun; Wang, Yen-Feng; Fuh, Jong-Ling; Wang, Shuu-Jiun

    2013-08-01

    The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) is unknown. Oxidative stress is detrimental to endothelial function and vascular reactivity. We hypothesized that the oxidative stress marker 8-iso-prostaglandin F2α, which is also a potent vasoconstrictor, might contribute to the pathogenesis of RCVS. Recruited participants included 103RCVS patients, 53 patients with primary headache with acute severe attacks, and 54 healthy controls. Subjects recruited prior to 2009 were discovery cohort, whereas those after 2009, replication cohort. Urine samples were obtained from all patients at registration and from 79 patients with RCVS again at remission stage. Urine 8-iso-prostaglandin F2α was analyzed by liquid chromatography-tandem mass spectrometry. Patients with RCVS received magnetic resonance angiography and transcranial color-coded sonography. In RCVS patients, the urine 8-iso-prostaglandin F2α level was higher than that in the other groups in discovery, replication, and combined cohorts (RCVS, 0.29±0.18; primary headache with acute severe attacks, 0.21±0.19; control, 0.18±0.09ng/mg creatinine; P<0.001), and it was positively correlated with the flow velocities of major intracranial arteries, especially within the first week of disease onset (middle cerebral artery, Spearman's correlation coefficient [rs]=0.580, P=0.002; anterior cerebral artery, rs=0.472, P=0.042; posterior cerebral artery, rs=0.457, P=0.022; basilar artery, rs= 0.530, P=0.002). The 8-iso-prostaglandin F2α level decreased from the ictalto remission stage in RCVS patients (0.31±0.21 vs 0.16±0.10ng/mg creatinine, P<0.001). 8-Iso-prostaglandin F2α was higher in patients with RCVS and correlated with the severity of vasoconstrictions. Further studies are required to explore its potential pathogenic role. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Role of oxidative stress on platelet hyperreactivity during aging.

    PubMed

    Fuentes, Eduardo; Palomo, Iván

    2016-03-01

    Thrombotic events are common causes of morbidity and mortality in the elderly. Age-accelerated vascular injury is commonly considered to result from increased oxidative stress. There is abundant evidence that oxidative stress regulate several components of thrombotic processes, including platelet activation. Thus oxidative stress can trigger platelet hyperreactivity by decreasing nitric oxide bioavailability. Therefore oxidative stress measurement may help in the early identification of asymptomatic subjects at risk of thrombosis. In addition, oxidative stress inhibitors and platelet-derived nitric oxide may represent a novel anti-aggregation/-activation approach. In this article the relative contribution of oxidative stress and platelet activation in aging is explored.

  18. Depletion of cytosolic or mitochondrial thioredoxin increases CYP2E1 induced oxidative stress via an ASK-1-JNK1 pathway in HepG2 cells

    PubMed Central

    Yang, Lili; Wu, Defeng; Wang, Xiaodong; Cederbaum, Arthur I

    2011-01-01

    Thioredoxin is an important reducing molecule in biological systems. Increasing CYP2E1 activity induces oxidative stress and cell toxicity. However, whether thioredoxin protects cells against CYP2E1 induced oxidative stress and toxicity is unknown. SiRNA were used to knockdown either cytosolic (TRX-1) or mitochondrial thioredoxin (TRX-2) in HepG2 cells expressing CYP2E1 (E47 cells) or without expressing CYP2E1 (C34 cells). Cell viability decreased 40–60% in E47 but not C34 cells with 80–90% knockdown of either TRX-1 or TRX-2. Depletion of either thioredoxin also potentiated the toxicity by either a glutathione synthesis inhibitor or TNFα in E47 cells. Generation of reactive oxygen species and 4-HNE protein adducts increased in E47 but not C34 cells with either thioredoxin knockdown. GSH was decreased and adding GSH completely blocked E47 cell death induced by either thioredoxin knockdown. Lowering TRX-1 or TRX-2 in E47 cells caused an early activation of ASK-1, followed by phosphorylation of JNK1 after 48 hrs of siRNA treatment. JNK inhibitor caused a partial recovery of E47 cell viability after thioredoxin knockdown. In conclusion, knockdown of TRX-1 or TRX-2 sensitizes cells to CYP2E1 induced oxidant stress partially via ASK-1 and JNK1 signaling pathways. Both TRX-1 and TRX-2 are important for defense against CYP2E1-induced oxidative stress. PMID:21557999

  19. Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: cochlear and cortical responses after an increase in antioxidant defense.

    PubMed

    Fetoni, Anna Rita; De Bartolo, Paola; Eramo, Sara Letizia Maria; Rolesi, Rolando; Paciello, Fabiola; Bergamini, Christian; Fato, Romana; Paludetti, Gaetano; Petrosini, Laura; Troiani, Diana

    2013-02-27

    This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q10 analog (Qter) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q9 and Q10 (CoQ9 and CoQ10, respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II-III and V-VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ10 analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ9 and CoQ10 content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway.

  20. Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

    PubMed

    Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

    2015-11-01

    The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

  1. Deletion of lec-10, a galectin-encoding gene, increases susceptibility to oxidative stress in Caenorhabditis elegans.

    PubMed

    Nemoto-Sasaki, Yoko; Kasai, Ken-ichi

    2009-12-01

    Galectins are a family of beta-galactoside-binding lectins. They are involved in the regulation of a variety of biological phenomena in mammals. However, little is known about their roles in invertebrates. Caenorhabditis elegans is a well-characterized model organism whose complete genome has been sequenced. C. elegans is now being studied extensively in various fields of medical sciences. In this study, we examined the phenotypes of a mutant strain of C. elegans (tm1262) lacking lec-10, a galectin-encoding gene. We observed no difference in the rates of embryonic lethality and larval arrest/slow growth between this mutant strain and the wild-type strain. No apparent morphological defect was observed in the lec-10-deletion mutant (tm1262). Moreover, the life-spans of this mutant and the wild-type strain were equivalent. However, this mutant showed significantly greater susceptibility to paraquat and hydrogen peroxide than the wild type did. The lec-10-deletion mutants (tm1262) were as susceptible as the daf-16-deletion mutants (mu86) to paraquat and hydrogen peroxide. These results suggest that the deletion of lec-10 does not have a notable effect on the worm's survival under laboratory conditions. However, this study indicates that lec-10 does confer some protection against oxidative stress.

  2. Precision-cut liver slices from diet-induced obese rats exposed to ethanol are susceptible to oxidative stress and increased fatty acid synthesis.

    PubMed

    Duryee, Michael J; Willis, Monte S; Schaffert, Courtney S; Reidelberger, Roger D; Dusad, Anand; Anderson, Daniel R; Klassen, Lynell W; Thiele, Geoffrey M

    2014-02-01

    Oxidative stress from fat accumulation in the liver has many deleterious effects. Many believe that there is a second hit that causes relatively benign fat accumulation to transform into liver failure. Therefore, we evaluated the effects of ethanol on ex vivo precision-cut liver slice cultures (PCLS) from rats fed a high-fat diet resulting in fatty liver. Age-matched male Sprague-Dawley rats were fed either high-fat (obese) (45% calories from fat, 4.73 kcal/g) or control diet for 13 mo. PCLS were prepared, incubated with 25 mM ethanol for 24, 48, and 72 h, harvested, and evaluated for ethanol metabolism, triglyceride production, oxidative stress, and cytokine expression. Ethanol metabolism and acetaldehyde production decreased in PCLS from obese rats compared with age-matched controls (AMC). Increased triglyceride and smooth muscle actin production was observed in PCLS from obese rats compared with AMC, which further increased following ethanol incubation. Lipid peroxidation, measured by thiobarbituric acid reactive substances assay, increased in response to ethanol, whereas GSH and heme oxygenase I levels were decreased. TNF-α and IL-6 levels were increased in the PCLS from obese rats and increased further with ethanol incubation. Diet-induced fatty liver increases the susceptibility of the liver to toxins such as ethanol, possibly by the increased oxidative stress and cytokine production. These findings support the concept that the development of fatty liver sensitizes the liver to the effects of ethanol and leads to the start of liver failure, necrosis, and eventually cirrhosis.

  3. Oxidative stress and glycemic regulation.

    PubMed

    Ceriello, A

    2000-02-01

    Oxidative stress is an acknowledged pathogenetic mechanism in diabetic complications. Hyperglycemia is a widely known cause of enhanced free radical concentration, whereas oxidative stress involvement in glycemic regulation is still debated. Glucose transport is a cascade of events starting from the interaction of insulin with its own receptor at the plasma membrane and ending with intracellular glucose metabolism. In this complex series of events, each step plays an important role and can be inhibited by a negative effect of oxidative stress. Several studies show that an acute increase in the blood glucose level may impair the physiological homeostasis of many systems in living organisms. The mechanisms through which acute hyperglycemia exerts these effects may be identified in the production of free radicals. It has been suggested that insulin resistance may be accompanied by intracellular production of free radicals. In adipocytes cultured in vitro, insulin increases the production of hydrogen peroxide, which has been shown to mimic the action of insulin. These data allow us to hypothesize that a vicious circle between hyperinsulinemia and free radicals could be operating: insulin resistance might cause elevated plasma free radical concentrations, which, in turn, might be responsible for a deterioration of insulin action, with hyperglycemia being a contributory factor. Data supporting this hypothesis are available. Vitamin E improves insulin action in healthy, elderly, and non-insulin-dependent diabetic subjects. Similar results can be obtained by vitamin C administration.

  4. AMPK-mediated increase of glycolysis as an adaptive response to oxidative stress in human cells: implication of the cell survival in mitochondrial diseases.

    PubMed

    Wu, Shi-Bei; Wei, Yau-Huei

    2012-02-01

    We report that the energy metabolism shifts to anaerobic glycolysis as an adaptive response to oxidative stress in the primary cultures of skin fibroblasts from patients with MERRF syndrome. In order to unravel the molecular mechanism involved in the alteration of energy metabolism under oxidative stress, we treated normal human skin fibroblasts (CCD-966SK cells) with sub-lethal doses of H(2)O(2). The results showed that several glycolytic enzymes including hexokinase type II (HK II), lactate dehydrogenase (LDH) and glucose transporter 1 (GLUT1) were up-regulated in H(2)O(2)-treated normal skin fibroblasts. In addition, the glycolytic flux of skin fibroblasts was increased by H(2)O(2) in a dose-dependent manner through the activation of AMP-activated protein kinase (AMPK) and phosphorylation of its downstream target, phosphofructokinase 2 (PFK2). Moreover, we found that the AMPK-mediated increase of glycolytic flux by H(2)O(2) was accompanied by an increase of intracellular NADPH content. By treatment of the cells with glycolysis inhibitors, an AMPK inhibitor or genetic knockdown of AMPK, respectively, the H(2)O(2)-induced increase of NADPH was abrogated leading to the overproduction of intracellular ROS and cell death. Significantly, we showed that phosphorylation levels of AMPK and glycolysis were up-regulated to confer an advantage of survival for MERRF skin fibroblasts. Taken together, our findings suggest that the increased production of NADPH by AMPK-mediated increase of the glycolytic flux contributes to the adaptation of MERRF skin fibroblasts and H(2)O(2)-treated normal skin fibroblasts to oxidative stress. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Manganese leads to an increase in markers of oxidative stress as well as to a shift in the ratio of Fe(II)/(III) in rat brain tissue.

    PubMed

    Fernsebner, Katharina; Zorn, Julia; Kanawati, Basem; Walker, Alesia; Michalke, Bernhard

    2014-04-01

    Occupationally or environmentally caused chronic exposure to Manganese (Mn) can lead to a degeneration of dopaminergic neurons inducing a Parkinson-like complaint called manganism. Deciphering the ongoing neurodegenerative mechanisms in the affected brain is still a major task for understanding the complex modes of action. Therefore, we applied a non-toxic, oral feeding in rats simulating a chronic exposure to Mn. Analysis of brain extracts by electrospray ionization Fourier transform resonance mass spectrometry (ESI-FT-ICR-MS) revealed an increase in markers of oxidative stress like glutathione disulfide (GSSG), prostaglandins, and 15(S)-HETE, a marker of lipid peroxidation. Furthermore, acetylcholinesterase (AchE) activity and glutamate concentrations were elevated in brain samples of Mn-supplemented rats, suggesting oxidative stress in the brain tissue. Application of ion chromatography coupled to inductively coupled plasma-optical emission spectrometry (IC-ICP-OES) further showed a shift of Fe(III) towards Fe(II) in the brain samples enabling for example the action of the Fenton reaction. This is the first time that changes in the Fe-species distribution could be related to Mn-induced neuroinflammation and is therefore enlarging the knowledge of this complex neurodegenerative condition. The combination of our findings provides substantial evidence that Mn-induced neuroinflammation leads to oxidative stress triggered by multifactorial pathophysiological processes.

  6. Leptin Administration Downregulates the Increased Expression Levels of Genes Related to Oxidative Stress and Inflammation in the Skeletal Muscle of ob/ob Mice

    PubMed Central

    Sáinz, Neira; Rodríguez, Amaia; Catalán, Victoria; Becerril, Sara; Ramírez, Beatriz; Gómez-Ambrosi, Javier; Frühbeck, Gema

    2010-01-01

    Obese leptin-deficient ob/ob mice exhibit a low-grade chronic inflammation together with a low muscle mass. Our aim was to analyze the changes in muscle expression levels of genes related to oxidative stress and inflammatory responses in leptin deficiency and to identify the effect of in vivo leptin administration. Ob/ob mice were divided in three groups as follows: control ob/ob, leptin-treated ob/ob (1 mg/kg/d) and leptin pair-fed ob/ob mice. Gastrocnemius weight was lower in control ob/ob than in wild type mice (P < .01) exhibiting an increase after leptin treatment compared to control and pair-fed (P < .01) ob/ob animals. Thiobarbituric acid reactive substances, markers of oxidative stress, were higher in serum (P < .01) and gastrocnemius (P = .05) of control ob/ob than in wild type mice and were significantly decreased (P < .01) by leptin treatment. Leptin deficiency altered the expression of 1,546 genes, while leptin treatment modified the regulation of 1,127 genes with 86 of them being involved in oxidative stress, immune defense and inflammatory response. Leptin administration decreased the high expression of Crybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1 and Serpinb1a observed in control ob/ob mice, indicating that it improves inflammation and muscle loss. PMID:20671928

  7. Low micromolar zinc exerts cytotoxic action under H2O2-induced oxidative stress: excessive increase in intracellular Zn2+ concentration.

    PubMed

    Matsui, Hiroko; Oyama, Tomohiro M; Okano, Yoshiro; Hashimoto, Erika; Kawanai, Takuya; Oyama, Yasuo

    2010-09-30

    The ability of zinc to retard oxidative processes has been recognized for many years. However, zinc is cytotoxic under certain oxidative stress. In this study, we investigated the effect of H2O2 on intracellular Zn2+ concentration of rat thymocytes and its relation to the cytotoxicity. Experiments were cytometrically performed by the use of fluorescent probes, propidium iodide, FluoZin-3-AM, and 5-chloromethylfluorescein diacetate. ZnCl2 potentiated cytotoxicity of H2O2 while TPEN, a chelator for intracellular Zn2+, attenuated it. Results suggested an involvement of intracellular Zn2+ in the cytotoxicity of H2O2. H2O2 at concentrations of 30microM or more (up to 1000microM) significantly increased intracellular Zn2+ concentration. There were two mechanisms. (1) H2O2 decreased cellular content of nonprotein thiols, possibly resulting in release of Zn2+ from thiols as cellular Zn2+ binding sites. (2) H2O2 increased membrane Zn2+ permeability because external ZnCl2 application further elevated intracellular Zn2+ concentration. Micromolar H2O2 may induce excessive elevation of intracellular Zn2+ concentration that is harmful to cellular functions. However, the incubation with micromolar ZnCl2 alone increased cellular content of nonprotein thiols, one of the factors protecting cells against oxidative stress. Though zinc is generally considered to be protective with its antioxidant property, this study reveals the toxic effect of zinc even in micromolar range under oxidative stress induced by H2O2. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Increased glyoxalase I levels inhibit accumulation of oxidative stress and an advanced glycation end product in mouse mesangial cells cultured in high glucose.

    PubMed

    Kim, Ki Mo; Kim, Young Sook; Jung, Dong Ho; Lee, Jun; Kim, Jin Sook

    2012-01-15

    Chronic high glucose levels lead to the formation of advanced glycation end-products (AGEs) as well as AGE precursors, such as methylglyoxal (MG) and glyoxal, via non-enzymatic glycation reactions in patients with diabetic mellitus. Glyoxalase 1 (GLO-1) detoxifies reactive dicarbonyls that form AGEs. To investigate the interaction between AGEs and GLO-1 in mesangial cells (MCs) under diabetic conditions, AGE levels and markers of oxidative stress were measured in GLO-1-overexpressing MCs (GLO-1-MCs) cultured in high glucose. Furthermore, we also examined levels of high glucose-induced apoptosis in GLO-1-MCs. In glomerular MCs, high glucose levels increased the formation of both MG and argpyrimidine (an MG-derived adduct) as well as GLO-1 expression. GLO-1-MCs had lower intracellular levels of MG accumulation, 8-hydroxy-deoxyguanosine (an oxidative DNA damage marker), 4-hydroxyl-2-nonenal (a lipid peroxidation product), and nitrosylated protein (a marker of oxidative-nitrosative stress) compared to control cells. Expression of mitochondrial oxidative phosphorylation complexes I, II, and III was also decreased in GLO-1-MCs. Furthermore, fewer GLO-1-MCs showed evidence of apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling assay, and activation of both poly (ADP-ribose) polymerase 1 cleavage and caspase-3 was lower in GLO-1-MCs than in control cells cultured in high glucose. These results suggest that GLO-1 plays a role in high glucose-mediated signaling by reducing MG accumulation and oxidative stress in diabetes mellitus. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  9. Increased dietary iron and radiation in rats promote oxidative stress, induce localized and systemic immune system responses, and alter colon mucosal environment.

    PubMed

    Morgan, Jennifer L L; Ritchie, Lauren E; Crucian, Brian E; Theriot, Corey; Wu, Honglu; Sams, Clarence; Smith, Scott M; Turner, Nancy D; Zwart, Sara R

    2014-03-01

    Astronauts are exposed to increased body iron stores and radiation, both of which can cause oxidative damage leading to negative health effects. The purpose of this study was to investigate combined effects of high dietary iron (650 mg/kg diet) and radiation exposure (0.375 Gy cesium-137 every other day for 16 d) on markers of oxidative stress, immune system function, and colon mucosal environment in male Sprague-Dawley rats (n=8/group). Control rats consumed adequate iron (45 mg/kg diet) and were not irradiated. Combined treatments increased liver glutathione peroxidase, serum catalase, and colon myeloperoxidase while decreasing total fecal short-chain fatty acid concentrations. The high-iron diet alone increased leukocyte count. Radiation decreased the T-cell CD4:CD8 ratio. Plasma iron was negatively correlated with cytokine production in activated monocytes. Genes involved in colon microbial signaling, immune response, and injury repair were altered by radiation. Genes involved with injury repair and pathogen recognition changed with dietary iron. These data demonstrate that dietary iron and radiation, alone and combined, contribute to oxidative stress that is related to immune system alterations in circulation and the colon. The model presented may help us better understand the changes to these systems that have been identified among astronauts.

  10. 17β-estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia.

    PubMed

    Dietrich, Alicia K; Humphreys, Gwendolyn I; Nardulli, Ann M

    2013-11-01

    While it is well established that 17β-estradiol (E2) protects the rodent brain from ischemia-induced damage, it has been unclear how this neuroprotective effect is mediated. Interestingly, convincing evidence has also demonstrated that maintaining or increasing the expression of the oxidative stress response and DNA repair protein apurinic endonuclease 1 (Ape1) is instrumental in reducing ischemia-induced damage in the brain. Since E2 increases expression of the oxidative stress response proteins Cu/Zn superoxide dismutase and thioredoxin in the brain, we hypothesized that E2 may also increase Ape1 expression and that this E2-induced expression of Ape1 may help to mediate the neuroprotective effects of E2 in the brain. To test this hypothesis, we utilized three model systems including primary cortical neurons, brain slice cultures, and whole animals. Although estrogen receptor α and Ape1 were expressed in primary cortical neurons, E2 did not alter Ape1 expression in these cells. However, immunofluorescent staining and quantitative Western blot analysis demonstrated that estrogen receptor α and Ape1 were expressed in the nuclei of cortical neurons in brain slice cultures and that E2 increased Ape1 expression in the cerebral cortex of these cultures. Furthermore, Ape1 expression was increased and oxidative DNA damage was decreased in the cerebral cortices of ovariectomized female C57Bl/6J mice that had been treated with E2 and exposed to hypoxia. Taken together, our studies demonstrate that the neuronal microenvironment may be required for increased Ape1 expression and that E2 enhances expression of Ape1 and reduces oxidative DNA damage, which may in turn help to reduce ischemia-induced damage in the cerebral cortex and mediate the neuroprotective effects of E2.

  11. [Magnesium and the oxidative stress].

    PubMed

    Spasov, A A; Zheltova, A A; Kharitonov, M V

    2012-07-01

    Magnesium deficiency has been shown to result in alterations of cellular functions and biological activity of molecules. The review discusses possible relationship between Mg2+ deficiency and development of oxidative stress. Decrease of Mg2+ concentration in tissues and blood is accompanied with elevation of the oxidative stress markers, including products of the oxidative modification of lipids, proteins and DNA. The reduction in antioxidant defenses is synchronous with oxidative stress markers elevation. Different mechanisms including systemic reactions (hyperactivation of inflammation and endothelial dysfunction) and cellular changes (mitochondrial dysfunction and excessive production of fatty acids) are supposed to be involved in development and maintenance of the oxidative stress due to Mg2+ deficiency. Therefore the facts consolidated into the review evidence clear relation between Mg2+ deficiency and the oxidative stress development.

  12. Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes

    PubMed Central

    Marinić, Jelena; Broznić, Dalibor; Milin, Čedomila

    2016-01-01

    Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE) on time-dependent changes in the hepatic oxidative state in a model of liver regeneration—a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight) or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2. PMID:26925195

  13. Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes.

    PubMed

    Marinić, Jelena; Broznić, Dalibor; Milin, Čedomila

    2016-01-01

    Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE) on time-dependent changes in the hepatic oxidative state in a model of liver regeneration-a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight) or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2.

  14. Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use

    PubMed Central

    Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J. A.; Bramness, Jørgen G.; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G.; Ramin, Pedram; Rousis, Nikolaos I.; Reid, Malcolm J.; Thomas, Kevin V.

    2016-01-01

    Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F2-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F2α (8-iso-PGF2α) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3′-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF2α, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF2α mass load was found to be strongly associated with that of trans-3′-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF2α as a wastewater biomarker for the assessment of community public health. PMID:27976726

  15. Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use.

    PubMed

    Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J A; Bramness, Jørgen G; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G; Ramin, Pedram; Rousis, Nikolaos I; Reid, Malcolm J; Thomas, Kevin V

    2016-12-15

    Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F2-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F2α (8-iso-PGF2α) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3'-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF2α, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF2α mass load was found to be strongly associated with that of trans-3'-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF2α as a wastewater biomarker for the assessment of community public health.

  16. Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use

    NASA Astrophysics Data System (ADS)

    Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J. A.; Bramness, Jørgen G.; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G.; Ramin, Pedram; Rousis, Nikolaos I.; Reid, Malcolm J.; Thomas, Kevin V.

    2016-12-01

    Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F2-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F2α (8-iso-PGF2α) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3‧-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF2α, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF2α mass load was found to be strongly associated with that of trans-3‧-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF2α as a wastewater biomarker for the assessment of community public health.

  17. The administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to cigarette smoke.

    PubMed

    Pena, Karina Braga; Ramos, Camila de Oliveira; Soares, Nícia Pedreira; da Silva, Pamela Félix; Bandeira, Ana Carla Balthar; Costa, Guilherme de Paula; Cangussú, Sílvia Dantas; Talvani, André; Bezerra, Frank Silva

    2016-01-01

    This study aimed to evaluate the effects of a high refined carbohydrate diet and pulmonary inflammatory response in C57BL/6 mice exposed to cigarette smoke (CS). Twenty-four male mice were divided into four groups: control group (CG), which received a standard diet; cigarette smoke group (CSG), which was exposed to CS; a high refined carbohydrate diet group (RG), which received a high refined carbohydrate diet; and a high refined carbohydrates diet and cigarette smoke group (RCSG), which received a high refined carbohydrate diet and was exposed to CS. The animals were monitored for food intake and body weight gain for 12 weeks. After this period, the CSG and RCSG were exposed to CS for five consecutive days. At the end of the experimental protocol, all animals were euthanized for subsequent analyses. There was an increase of inflammatory cells in the bronchoalveolar lavage fluid (BALF) of CSG compared to CG and RCSG compared to CG, CSG, and RG. In addition, in the BALF, there was an increase of tumor necrosis factor alpha in RCSG compared to CG, CSG, and RG; interferon gamma increase in RCSG compared to the CSG; and increase in interleukin-10 in RCSG compared to CG and RG. Lipid peroxidation increased in RCSG compared to CG, CSG, and RG. Furthermore, the oxidation of proteins increased in CSG compared to CG. The analysis of oxidative stress showed an increase in superoxide dismutase in RCSG compared to CG, CSG, and RG and an increase in the catalase activity in RCSG compared with CG. In addition, there was a decrease in the glutathione reduced/glutathione total ratio of CSG, RG, and RCSG compared to CG. Therefore, the administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to CS.

  18. The administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to cigarette smoke

    PubMed Central

    Pena, Karina Braga; Ramos, Camila de Oliveira; Soares, Nícia Pedreira; da Silva, Pamela Félix; Bandeira, Ana Carla Balthar; Costa, Guilherme de Paula; Cangussú, Sílvia Dantas; Talvani, André; Bezerra, Frank Silva

    2016-01-01

    This study aimed to evaluate the effects of a high refined carbohydrate diet and pulmonary inflammatory response in C57BL/6 mice exposed to cigarette smoke (CS). Twenty-four male mice were divided into four groups: control group (CG), which received a standard diet; cigarette smoke group (CSG), which was exposed to CS; a high refined carbohydrate diet group (RG), which received a high refined carbohydrate diet; and a high refined carbohydrates diet and cigarette smoke group (RCSG), which received a high refined carbohydrate diet and was exposed to CS. The animals were monitored for food intake and body weight gain for 12 weeks. After this period, the CSG and RCSG were exposed to CS for five consecutive days. At the end of the experimental protocol, all animals were euthanized for subsequent analyses. There was an increase of inflammatory cells in the bronchoalveolar lavage fluid (BALF) of CSG compared to CG and RCSG compared to CG, CSG, and RG. In addition, in the BALF, there was an increase of tumor necrosis factor alpha in RCSG compared to CG, CSG, and RG; interferon gamma increase in RCSG compared to the CSG; and increase in interleukin-10 in RCSG compared to CG and RG. Lipid peroxidation increased in RCSG compared to CG, CSG, and RG. Furthermore, the oxidation of proteins increased in CSG compared to CG. The analysis of oxidative stress showed an increase in superoxide dismutase in RCSG compared to CG, CSG, and RG and an increase in the catalase activity in RCSG compared with CG. In addition, there was a decrease in the glutathione reduced/glutathione total ratio of CSG, RG, and RCSG compared to CG. Therefore, the administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to CS. PMID:28008246

  19. [Oxidative stress and endothelial dysfunction].

    PubMed

    Jarasūniene, Dalia; Simaitis, Audrius

    2003-01-01

    Growing numbers of morbidity and mortality due to the Coronary Heart Disease (CHD) is recognized as the more increasing challenge in the world. The initial stage of atherosclerosis, early diagnosis and treatment of CHD are the main objectives of current research. Endothelium dysfunction, the earliest expression of the atherosclerotic process is associated with subtle biochemical changes that gradually are transformed into the structural changes of the arterial wall. The theory of free radicals is the most common among the atherosclerosis explanations. Overproduction or impaired neutralization of the free radicals accounts for oxidative stress that is causing substantial damage to the low density lipoproteins, nitric oxyde (NO), endothelium cells, tissue cells and finally leads to the endothelium dysfuction. Pathophysiology of oxidative stress and its role in the endothelium dysfunction are discussed in this paper. Positive role of various medications (statins, angiotensin converting enzym inhibitors, aldosteron antagonists, estrogens, antioxidants, b-blockers with vasodilatative properties) to the oxidative stress and consequently to the endothelium dysfuction are discussed as well.

  20. Increased blood oxidative stress in experimental menopause rat model: the effects of vitamin A low-dose supplementation upon antioxidant status in bilateral ovariectomized rats.

    PubMed

    Behr, Guilherme Antônio; Schnorr, Carlos Eduardo; Moreira, José Cláudio Fonseca

    2012-04-01

    Menopause has been reported to be associated with increased oxidative stress and metabolic disorders among women worldwide. Disarrangements in the redox state similar to those observed in women during the decline of ovarian hormonal activity can be obtained experimentally through rat bilateral ovariectomy. The search for alternative treatments to improve life quality in postmenopausal woman is really important. The aim of this study was to evaluate biochemical and oxidative stress parameters that distinguish sham-operated female rats from Wistar rats bilaterally ovariectomized (OVX). Additionally, we have also investigated the effects of retinol palmitate (a vitamin A supplement) low-dose supplementation (500 or 1500 IU/kg/day, during 30 days) upon blood and plasma antioxidant status in OVX rats. Ovariectomy caused an increase in body weight gain, pronounced uterine atrophy, decreased plasma triglycerides and increased total cholesterol levels, and reduced acid uric content. Moreover, we found increased blood peroxidase activities (catalase and glutathione peroxidase), decreased plasma non-enzymatic antioxidant defenses total reactive antioxidant potential and total antioxidant reactivity, decreased protein and non-protein SH levels, accompanied by increased protein oxidative damage (carbonyl). In addition, vitamin A low-dose supplementation was capable to ameliorate antioxidant status in OVX rats, restoring both enzymatic and non-enzymatic defenses, promoting reduction in plasma SH content, and decreasing protein oxidative damage levels. This is the first work in the literature showing that vitamin A at low dose may be beneficial in the treatment of menopause symptoms. Further studies will be made to better understand the effects of vitamin A supplementation in menopause rat model.

  1. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress.

    PubMed

    Liu, Dong; Chan, Sic L; de Souza-Pinto, Nadja C; Slevin, John R; Wersto, Robert P; Zhan, Ming; Mustafa, Khadija; de Cabo, Rafael; Mattson, Mark P

    2006-01-01

    The high-metabolic demand of neurons and their reliance on glucose as an energy source places them at risk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential (Deltapsim) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements. Neural cells with increased levels of UCP4 exhibit decreased Deltapsim, reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of Deltapsim to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing glucose uptake and shifting the mode of ATP production from mitochondrial respiration to glycolysis, thereby maintaining cellular ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload.

  2. Willow bark extract increases antioxidant enzymes and reduces oxidative stress through activation of Nrf2 in vascular endothelial cells and Caenorhabditis elegans.

    PubMed

    Ishikado, Atsushi; Sono, Yoko; Matsumoto, Motonobu; Robida-Stubbs, Stacey; Okuno, Aya; Goto, Masashi; King, George L; Blackwell, T Keith; Makino, Taketoshi

    2013-12-01

    Willow bark extract (WBE) is listed in the European Pharmacopoeia and has been traditionally used for treating fever, pain, and inflammation. Recent studies have demonstrated its clinical usefulness. This study investigated the antioxidative effects of WBE in human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. WBE prevented oxidative-stress-induced cytotoxicity of HUVECs and death of C. elegans. WBE dose-dependently increased mRNA and protein expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) target genes heme oxygenase-1, γ-glutamylcysteine ligase modifier and catalytic subunits, and p62 and intracellular glutathione (GSH) in HUVECs. In the nematode C. elegans, WBE increased the expression of the gcs-1::green fluorescent protein reporter, a well-characterized target of the Nrf2 ortholog SKN-1, in a manner that was SKN-1-dependent. WBE increased intranuclear expression and DNA binding of Nrf2 and the activity of an antioxidant response element (ARE) reporter plasmid in HUVECs. WBE-induced expression of Nrf2-regulated genes and increased GSH levels in HUVECs were reduced by Nrf2 and p38 small interfering (si) RNAs and by the p38-specific inhibitor SB203580. Nrf2 siRNA reduced the cytoprotective effect of WBE against oxidative stress in HUVECs. Salicin, a major anti-inflammatory ingredient of WBE, failed to activate ARE-luciferase activity, whereas a salicin-free WBE fraction showed intensive activity. WBE induced antioxidant enzymes and prevented oxidative stress through activation of Nrf2 independent of salicin, providing a new potential explanation for the clinical usefulness of WBE. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. [Vitamins and oxidative stress].

    PubMed

    Kodentsova, V M; Vrzhesinskaia, O A; Mazo, V K

    2013-01-01

    The central and local stress limiting systems, including the antioxidant defense system involved in defending the organism at the cellular and systemic levels from excess activation response to stress influence, leading to damaging effects. The development of stress, regardless of its nature [cold, increased physical activity, aging, the development of many pathologies (cardiovascular, neurodegenerative diseases, diseases of the gastrointestinal tract, ischemia, the effects of burns), immobilization, hypobaric hypoxia, hyperoxia, radiation effects etc.] leads to a deterioration of the vitamin status (vitamins E, A, C). Damaging effect on the antioxidant defense system is more pronounced compared to the stress response in animals with an isolated deficiency of vitamins C, A, E, B1 or B6 and the combined vitamins deficiency in the diet. Addition missing vitamin or vitamins restores the performance of antioxidant system. Thus, the role of vitamins in adaptation to stressors is evident. However, vitamins C, E and beta-carotene in high doses, significantly higher than the physiological needs of the organism, may be not only antioxidants, but may have also prooxidant properties. Perhaps this explains the lack of positive effects of antioxidant vitamins used in extreme doses for a long time described in some publications. There is no doubt that to justify the current optimal doses of antioxidant vitamins and other dietary antioxidants specially-designed studies, including biochemical testing of initial vitamin and antioxidant status of the organism, as well as monitoring their change over time are required.

  4. Indoxyl Sulfate Affects Glial Function Increasing Oxidative Stress and Neuroinflammation in Chronic Kidney Disease: Interaction between Astrocytes and Microglia.

    PubMed

    Adesso, Simona; Magnus, Tim; Cuzzocrea, Salvatore; Campolo, Michela; Rissiek, Björn; Paciello, Orlando; Autore, Giuseppina; Pinto, Aldo; Marzocco, Stefania

    2017-01-01

    Indoxyl sulfate (IS) is a protein-bound uremic toxin resulting from the metabolism of dietary tryptophan which accumulates in patients with impaired renal function, such as chronic kidney disease (CKD). IS is a well-known nephrovascular toxin but little is known about its effects on central nervous system (CNS) cells. Considering the growing interest in the field of CNS comorbidities in CKD, we studied the effect of IS on CNS cells. IS (15-60 μM) treatment in C6 astrocyte cells increased reactive oxygen species release and decreased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation, and heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 expression. Moreover, IS increased Aryl hydrocarbon Receptor (AhR) and Nuclear Factor-kB (NF-kB) activation in these cells. Similiar observations were made in primary mouse astrocytes and mixed glial cells. Inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression, tumor necrosis factor-α and interleukin-6 release and nitrotyrosine formation were increased by IS (15-60 μM) in primary mouse astrocytes and mixed glial cells. IS increased AhR and NF-kB nuclear translocation and reduced Nrf2 translocation and HO-1 expression in primary glial cells. In addition, IS induced cell death in neurons in a dose dependent fashion. Injection of IS (800 mg/kg, i.p.) into mice induced histological changes and increased COX-2 expression and nitrotyrosine formation in thebrain tissue. Taken together, our results show a significant contribution of IS in generating a neurotoxic enviroment and it could also have a potential role in neurodegeneration. IS could be considered also a potential therapeutical target for CKD-associated neurodegenerative complications.

  5. Indoxyl Sulfate Affects Glial Function Increasing Oxidative Stress and Neuroinflammation in Chronic Kidney Disease: Interaction between Astrocytes and Microglia

    PubMed Central

    Adesso, Simona; Magnus, Tim; Cuzzocrea, Salvatore; Campolo, Michela; Rissiek, Björn; Paciello, Orlando; Autore, Giuseppina; Pinto, Aldo; Marzocco, Stefania

    2017-01-01

    Indoxyl sulfate (IS) is a protein-bound uremic toxin resulting from the metabolism of dietary tryptophan which accumulates in patients with impaired renal function, such as chronic kidney disease (CKD). IS is a well-known nephrovascular toxin but little is known about its effects on central nervous system (CNS) cells. Considering the growing interest in the field of CNS comorbidities in CKD, we studied the effect of IS on CNS cells. IS (15–60 μM) treatment in C6 astrocyte cells increased reactive oxygen species release and decreased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation, and heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 expression. Moreover, IS increased Aryl hydrocarbon Receptor (AhR) and Nuclear Factor-kB (NF-kB) activation in these cells. Similiar observations were made in primary mouse astrocytes and mixed glial cells. Inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression, tumor necrosis factor-α and interleukin-6 release and nitrotyrosine formation were increased by IS (15–60 μM) in primary mouse astrocytes and mixed glial cells. IS increased AhR and NF-kB nuclear translocation and reduced Nrf2 translocation and HO-1 expression in primary glial cells. In addition, IS induced cell death in neurons in a dose dependent fashion. Injection of IS (800 mg/kg, i.p.) into mice induced histological changes and increased COX-2 expression and nitrotyrosine formation in thebrain tissue. Taken together, our results show a significant contribution of IS in generating a neurotoxic enviroment and it could also have a potential role in neurodegeneration. IS could be considered also a potential therapeutical target for CKD-associated neurodegenerative complications. PMID:28659803

  6. Pressure overload-induced mild cardiac hypertrophy reduces left ventricular transmural differences in mitochondrial respiratory chain activity and increases oxidative stress

    PubMed Central

    Kindo, Michel; Gerelli, Sébastien; Bouitbir, Jamal; Charles, Anne-Laure; Zoll, Joffrey; Hoang Minh, Tam; Monassier, Laurent; Favret, Fabrice; Piquard, François; Geny, Bernard

    2012-01-01

    Objective: Increased mechanical stress and contractility characterizes normal left ventricular (LV) subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced LV hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n = 10 for each group). Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilized fibers, Amplex Red fluorescence and citrate synthase activity. Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (−36.7%, P < 0.01) and complex IV activity (−57.4%, P < 0.05). Mitochondrial hydrogen peroxide (H2O2) production was similar in both LV layers. Aortic banding induced mild LVH (+31.7% LV mass), associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (−23.6 and −33.3%), increased mitochondrial H2O2 production (+86.9 and +73.1%), free radical leak (+27.2% and +36.3%) and citrate synthase activity (+27.2% and +36.3%) in Endo and Epi, respectively. Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (−57.4 vs. −12.2%; P = 0.02). Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH. PMID:22934079

  7. Ziram and sodium N,N-dimethyldithiocarbamate inhibit ubiquitin activation through intracellular metal transport and increased oxidative stress in HEK293 cells.

    PubMed

    Dennis, Kathleen E; Valentine, William M

    2015-04-20

    Ubiquitin activating enzyme E1 plays a pivotal role in ubiquitin based protein signaling through regulating the initiating step of the cascade. Previous studies demonstrated that E1 is inhibited by covalent modification of reactive cysteines contained within the ubiquitin-binding groove and by conditions that increase oxidative stress and deplete cellular antioxidants. In this study, we determined the relative contribution of covalent adduction and oxidative stress to E1 inhibition produced by ziram and sodium N,N-dimethyldithiocarbamate (DMDC) in HEK293 cells. Although no dithiocarbamate-derived E1 adducts were identified on E1 using shotgun LC/MS/MS for either ziram or DMDC, both dithiocarbamates significantly decreased E1 activity, with ziram demonstrating greater potency. Ziram increased intracellular levels of zinc and copper, DMDC increased intracellular levels of only copper, and both dithiocarbamates enhanced oxidative injury evidenced by elevated levels of protein carbonyls and expression of heme oxygenase-1. To assess the contribution of intracellular copper transport to E1 inhibition, coincubations were performed with the copper chelator triethylenetetramine hydrochloride (TET). TET significantly protected E1 activity for both of the dithiocarbamates and decreased the associated oxidative injury in HEK293 cells as well as prevented dithiocarbamate-mediated lipid peroxidation assayed using an ethyl aracidonate micelle system. Because TET did not completely ameliorate intracellular transport of copper or zinc for ziram, TET apparently maintained E1 activity through its ability to diminish dithiocarbamate-mediated oxidative stress. Experiments to determine the relative contribution of elevated intracellular zinc and copper were performed using a metal free incubation system and showed that increases in either metal were sufficient to inhibit E1. To evaluate the utility of the HEK293 in vitro system for screening environmental agents, a series of additional

  8. Low-level laser therapy (904nm) can increase collagen and reduce oxidative and nitrosative stress in diabetic wounded mouse skin.

    PubMed

    Tatmatsu-Rocha, José Carlos; Ferraresi, Cleber; Hamblin, Michael R; Damasceno Maia, Flávio; do Nascimento, Nilberto Robson Falcão; Driusso, Patricia; Parizotto, Nivaldo Antonio

    2016-11-01

    Over the last decade we have seen an increased interest in the use of Low-Level Laser Therapy (LLLT) in diseases that involve increased oxidative stress. It is well established that hyperglycemia in diabetes elicits a rise in reactive oxygen species (ROS) production but the effect of LLLT remains unclear. This study aimed to investigate whether LLLT was able to improve oxidative/nitrosative stress parameters in the wound healing process in diabetic mice. Twenty male mice were divided into four groups: non-irradiated control (NIC), irradiated control (IC), non-irradiated and diabetic (NID), irradiated and diabetic (ID). Diabetes was induced by administration of streptozotocin. Wounds were created 120days after the induction of diabetes in groups IC and ID and these groups were irradiated daily for 5days (superpulsed 904nm laser, average power 40mW, 60s). All animals were sacrificed 1day after the last irradiation and histology, collagen amount, catalase activity, nitrite and thiobarbituric acid reactive substances (TBARS) were measured. Histology showed that collagen fibers were more organized in IC and ID when compared to NID group, and significant differences in collagen content were found in group ID versus NID. Catalase activity was higher in IC group compared to other groups (p<0.001). TBARS levels were higher in IC versus NIC, but were lower in ID versus NID (p<0.001). Nitrite was lower in both irradiated groups versus the respective non-irradiated groups (p<0.001). Delayed wound healing in diabetes is still a challenge in clinical practice with high social costs. The increased production of collagen and decreased oxidative and nitrosative stress suggests that LLLT may be a viable therapeutic alternative in diabetic wound healing. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.

    PubMed

    Huang, Yun-Ching; Chin, Chih-Chien; Chen, Chih-Shou; Shindel, Alan W; Ho, Dong-Ru; Lin, Ching-Shwun; Shi, Chung-Sheng

    2015-01-01

    Cigarette use is an independent risk factor for the development of erectile dysfunction (ED). While the association between chronic smoking and ED is well established, the fundamental mechanism(s) of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS) for 4 weeks (n = 10), 12 weeks (n = 10), and 24 weeks (n = 10). At the 24-week time point all rats were assessed with intracavernous pressure (ICP) during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS). Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP) was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.

  10. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model

    PubMed Central

    Huang, Yun-Ching; Chin, Chih-Chien; Chen, Chih-Shou; Shindel, Alan. W.; Ho, Dong-Ru; Lin, Ching-Shwun; Shi, Chung-Sheng

    2015-01-01

    Cigarette use is an independent risk factor for the development of erectile dysfunction (ED). While the association between chronic smoking and ED is well established, the fundamental mechanism(s) of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS) for 4 weeks (n = 10), 12 weeks (n = 10), and 24 weeks (n = 10). At the 24-week time point all rats were assessed with intracavernous pressure (ICP) during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS). Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP) was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED. PMID:26491965

  11. Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress.

    PubMed

    Main, Penelope A E; Thomas, Philip; Esterman, Adrian; Fenech, Michael F

    2013-07-01

    Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case-sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally

  12. Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress

    PubMed Central

    Fenech, Michael F.

    2013-01-01

    Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case–sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally

  13. Clinical Relevance of Biomarkers of Oxidative Stress

    PubMed Central

    Frijhoff, Jeroen; Winyard, Paul G.; Zarkovic, Neven; Davies, Sean S.; Stocker, Roland; Cheng, David; Knight, Annie R.; Taylor, Emma Louise; Oettrich, Jeannette; Ruskovska, Tatjana; Gasparovic, Ana Cipak; Cuadrado, Antonio; Weber, Daniela; Poulsen, Henrik Enghusen; Grune, Tilman; Schmidt, Harald H.H.W.

    2015-01-01

    Abstract Significance: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. Critical Issues: The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. Future Directions: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 23, 1144–1170. PMID:26415143

  14. Ischemia-modified albumin (IMA) is increased in patients with chronic hepatitis C infection and related to markers of oxidative stress and inflammation.

    PubMed

    Zuwała-Jagiełło, Jolanta; Warwas, Maria; Pazgan-Simon, Monika

    2012-01-01

    Inflammation and oxidative stress have been reported in patients with chronic hepatitis C (CHC) infection, but their influence on ischemia-modified albumin (IMA) levels and diabetes prevalence remains unknown. Sixty-three CHC patients, 28 with diabetes, and 40 healthy controls were enrolled in the study. Circulating levels of oxidative stress markers [Nε-(carboxymethyl)lysine- advanced glycation end products (CML-AGEs) and advanced oxidation protein products-(AOPPs)], pro-inflammatory cytokines (interleukin-6, and tumor necrosis factor α), and high-sensitivity C-reactive protein (hsCRP) were assessed. Compared with the controls, the CHC patients with diabetes showed a significant increase in plasma concentrations of IMA, AOPPs, interleukin-6 and hsCRP (P < 0.05). The values of IMA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were found between hsCRP and presence of diabetes, IMA (both P < 0.01) and AOPP levels (P < 0.05). CML-AGEs did not show any significant correlation with IMA, markers of inflammation and presence of diabetes. In conclusion, we have documented significant elevation in plasma levels of IMA and AOPPs in CHC patients. In addition, circulating IMA was associated with inflammation markers and diabetes prevalence. This observation suggests a relationship between IMA and inflammation in CHC patients with diabetes, which may represent one of the mechanisms involved in the accelerated atherosclerosis in this population.

  15. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally-aging mice

    PubMed Central

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Michelle Jennifer; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-01-01

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer’s disease and normal aging is understudied. In the present study we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer’s disease, by crossing APP/PSEN1+ bigenic mice with SVCT2+/− heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2+/− mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2+/− and APP/PSEN1+, mice, and the combination genotype SVCT2+/−APP/PSEN1+, were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2+/−) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2+/− mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2+/−APP/PSEN1+ mice compared to APP/PSEN1+ mice with normal brain vitamin C. The data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways. PMID:25642732

  16. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

    PubMed

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Jennifer Michelle; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-04-15

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

  17. Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure.

    PubMed

    Bouch, Sheena; O'Reilly, Megan; Harding, Richard; Sozo, Foula

    2015-09-01

    Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21% O2), mild (40% O2), or moderate (65% O2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects) or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress [heme oxygenase-1 (HO-1) and nitrotyrosine staining] and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65% O2 group than in the 21% O2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40% O2 and 65% O2 groups relative to the 21% O2 group. Exposure to 65% O2, but not 40% O2, led to larger alveoli and lower tissue fraction in the short term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40% O2 or 65% O2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65% O2, 40% O2 does not affect lung architecture.

  18. Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and l-DOPA reversible motor deficits.

    PubMed

    Masoud, S T; Vecchio, L M; Bergeron, Y; Hossain, M M; Nguyen, L T; Bermejo, M K; Kile, B; Sotnikova, T D; Siesser, W B; Gainetdinov, R R; Wightman, R M; Caron, M G; Richardson, J R; Miller, G W; Ramsey, A J; Cyr, M; Salahpour, A

    2015-02-01

    The dopamine transporter is a key protein responsible for regulating dopamine homeostasis. Its function is to transport dopamine from the extracellular space into the presynaptic neuron. Studies have suggested that accumulation of dopamine in the cytosol can trigger oxidative stress and neurotoxicity. Previously, ectopic expression of the dopamine transporter was shown to cause damage in non-dopaminergic neurons due to their inability to handle cytosolic dopamine. However, it is unknown whether increasing dopamine transporter activity will be detrimental to dopamine neurons that are inherently capable of storing and degrading dopamine. To address this issue, we characterized transgenic mice that over-express the dopamine transporter selectively in dopamine neurons. We report that dopamine transporter over-expressing (DAT-tg) mice display spontaneous loss of midbrain dopamine neurons that is accompanied by increases in oxidative stress markers, 5-S-cysteinyl-dopamine and 5-S-cysteinyl-DOPAC. In addition, metabolite-to-dopamine ratios are increased and VMAT2 protein expression is decreased in the striatum of these animals. Furthermore, DAT-tg mice also show fine motor deficits on challenging beam traversal that are reversed with l-DOPA treatment. Collectively, our findings demonstrate that even in neurons that routinely handle dopamine, increased uptake of this neurotransmitter through the dopamine transporter results in oxidative damage, neuronal loss and l-DOPA reversible motor deficits. In addition, DAT over-expressing animals are highly sensitive to MPTP-induced neurotoxicity. The effects of increased dopamine uptake in these transgenic mice could shed light on the unique vulnerability of dopamine neurons in Parkinson's disease.

  19. Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits

    PubMed Central

    Masoud, ST; Vecchio, LM; Bergeron, Y; Hossain, MM; Nguyen, LT; Bermejo, MK; Kile, B; Sotnikova, TD; Siesser, WB; Gainetdinov, RR; Wightman, RM; Caron, MG; Richardson, JR; Miller, GW; Ramsey, AJ; Cyr, M; Salahpour, A

    2015-01-01

    The dopamine transporter is a key protein responsible for regulating dopamine homeostasis. Its function is to transport dopamine from the extracellular space into the presynaptic neuron. Studies have suggested that accumulation of dopamine in the cytosol can trigger oxidative stress and neurotoxicity. Previously, ectopic expression of the dopamine transporter was shown to cause damage in non-dopaminergic neurons due to their inability to handle cytosolic dopamine. However, it is unknown whether increasing dopamine transporter activity will be detrimental to dopamine neurons that are inherently capable of storing and degrading dopamine. To address this issue, we characterized transgenic mice that over-express the dopamine transporter selectively in dopamine neurons. We report that dopamine transporter over-expressing (DAT-tg) mice display spontaneous loss of midbrain dopamine neurons that is accompanied by increases in oxidative stress markers, 5-S-cysteinyl-dopamine and 5-S-cysteinyl-DOPAC. In addition, metabolite-to-dopamine ratios are increased and VMAT2 protein expression is decreased in the striatum of these animals. Furthermore, DAT-tg mice also show fine motor deficits on challenging beam traversal that are reversed with L-DOPA treatment. Collectively, our findings demonstrate that even in neurons that routinely handle dopamine, increased uptake of this neurotransmitter through the dopamine transporter results in oxidative damage, neuronal loss and LDOPA reversible motor deficits. In addition, DAT over-expressing animals are highly sensitive to MPTP-induced neurotoxicity. The effects of increased dopamine uptake in these transgenic mice could shed light on the unique vulnerability of dopamine neurons in Parkinson’s disease. PMID:25447236

  20. Increasing the Vegetable Intake Dose Is Associated with a Rise in Plasma Carotenoids without Modifying Oxidative Stress or Inflammation in Overweight or Obese Postmenopausal Women123

    PubMed Central

    Crane, Tracy E.; Kubota, Chieri; West, Julie L.; Kroggel, Mark A.; Wertheim, Betsy C.; Thomson, Cynthia A.

    2011-01-01

    The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women. PMID:21865569

  1. Increasing the repeating units of ethylene glycol-based dimethacrylates directed toward reduced oxidative stress and co-stimulatory factors expression in human monocytic cells.

    PubMed

    Tamura, Atsushi; Fukumoto, Izumi; Yui, Nobuhiko; Matsumura, Mitsuaki; Miura, Hiroyuki

    2015-03-01

    The ethylene glycol-based dimethacrylates are commonly used in biomaterials and dental restorative materials as a cross-linking agent. In this study, toxic effect of triethylene glycol dimethacrylate (TEGDMA) and poly(ethylene glycol) dimethacrylates (PEG-DMAs) with various ethylene glycol repeating units was investigated in terms of cytotoxicity, oxidative stress, and the expression of co-stimulatory factors in human leukemia cell line (THP-1 cells) to verify the effect of ethylene glycol repeating units. Note that the 1-octanol/water partition coefficient of PEG-based dimethacrylates decreased with increasing the ethylene glycol repeating units, indicating that the hydrophilicity of PEG-DMAs increased with ethylene glycol repeating units. The toxic effect of PEG-DMAs such as cytotoxicity, oxidative stress, and the expression of CD86 in treated THP-1 cells are reduced with increasing the ethylene glycol repeating units in PEG-DMAs. However, the expression of CD54 in treated THP-1 cells was not influenced with the ethylene glycol repeating units and the maximal expression level of CD54 was observed at the concentration range of 2-4 mM for all samples. Accordingly, hydrophilic character of PEG-DMAs with long ethylene glycol chains definitely alleviates the some toxic aspect of PEG-based DMAs. This finding would provide important insight into the design of new biomaterials and dental materials with superior biocompatibility. © 2014 Wiley Periodicals, Inc.

  2. Hydrogen sulfide releasing aspirin, ACS14, attenuates high glucose-induced increased methylglyoxal and oxidative stress in cultured vascular smooth muscle cells.

    PubMed

    Huang, Qian; Sparatore, Anna; Del Soldato, Piero; Wu, Lingyun; Desai, Kaushik

    2014-01-01

    Hydrogen sulfide is a gasotransmitter with vasodilatory and anti-inflammatory properties. Aspirin is an irreversible cyclooxygenase inhibitor anti-inflammatory drug. ACS14 is a novel synthetic hydrogen sulfide releasing aspirin which inhibits cyclooxygenase and has antioxidant effects. Methylglyoxal is a chemically active metabolite of glucose and fructose, and a major precursor of advanced glycation end products formation. Methylglyoxal is harmful when produced in excess. Plasma methylglyoxal levels are significantly elevated in diabetic patients. Our aim was to investigate the effects of ACS14 on methylglyoxal levels in cultured rat aortic vascular smooth muscle cells. We used cultured rat aortic vascular smooth muscle cells for the study. Methylglyoxal was measured by HPLC after derivatization, and nitrite+nitrate with an assay kit. Western blotting was used to determine NADPH oxidase 4 (NOX4) and inducible nitric oxide synthase (iNOS) protein expression. Dicholorofluorescein assay was used to measure oxidative stress. ACS14 significantly attenuated elevation of intracellular methylglyoxal levels caused by incubating cultured vascular smooth muscle cells with methylglyoxal (30 µM) and high glucose (25 mM). ACS14, but not aspirin, caused a significant attenuation of increase in nitrite+nitrate levels caused by methylglyoxal or high glucose. ACS14, aspirin, and sodium hydrogen sulfide (NaHS, a hydrogen sulfide donor), all attenuated the increase in oxidative stress caused by methylglyoxal and high glucose in cultured cells. ACS14 prevented the increase in NOX4 expression caused by incubating the cultured VSMCs with MG (30 µM). ACS14, aspirin and NaHS attenuated the increase in iNOS expression caused by high glucose (25 mM). In conclusion, ACS14 has the novel ability to attenuate an increase in methylglyoxal levels which in turn can reduce oxidative stress, decrease the formation of advanced glycation end products and prevent many of the known deleterious effects

  3. Role of NADPH oxidases in inducing a selective increase of oxidant stress and cyclin D1 and checkpoint 1 over-expression during progression to human gastric adenocarcinoma.

    PubMed

    Montalvo-Javé, Eduardo E; Olguín-Martínez, Marisela; Hernández-Espinosa, Diego R; Sánchez-Sevilla, Lourdes; Mendieta-Condado, Edgar; Contreras-Zentella, Martha L; Oñate-Ocaña, Luis F; Escalante-Tatersfield, Tomás; Echegaray-Donde, Agustín; Ruiz-Molina, Juan M; Herrera, Miguel F; Morán, Julio; Hernández-Muñoz, Rolando

    2016-04-01

    Gastric cancer is one of the main causes of global mortality. Here, reactive oxygen species (ROS) could largely contribute to gastric carcinogenesis. Hence, the present work was aimed to assess the role of ROS, oxidant status, NADPH oxidases (NOXs) expression, during human gastric adenocarcinoma. We obtained subcellular fraction from samples of gastric mucosa taken from control subjects (n = 20), and from 40 patients with gastric adenocarcinoma, as well as samples of distant areas (tumour-free gastric mucosa). Parameters indicative of lipid peroxidation and cell proliferation were selectively increased in both tumour-free and in cancerous gastric mucosa, despite of glutathione (GSH) content, glutathione reductase (GR) and superoxide dismutase (SOD) activities were increased in the adenocarcinoma. These high levels of antioxidant defences inversely correlated with down-regulated expression for NOX2 and 4; however, over-expression of NOX1 occurred with increased caspase-3 activity and overexpressed checkpoint 1 (MDC1) and cyclin D1 proteins. In the tumour-free mucosa an oxidant stress took place, without changing total GSH but with decreased activities for GR and mitochondrial SOD; moreover, over-expression of checkpoint 1 (MDC1) correlated with lower NOX2 and 4 expression in this mucosa. Chronically injured gastric mucosa increases lipoperoxidative events and cell proliferation. In the adenocarcinoma, cell proliferation was further enhanced, oxidant stress decreased which seemed to be linked to NOX1, MDC1 and cyclin D1 over-expression, but with a lower NOXs activity leading a 'low tone' of ROS formation. Therefore, our results could be useful for early detection and treatment of gastric adenocarcinoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Increased vitamin e content in the lung after ozone exposure: A possible mobilization in response to oxidative stress. (Reannouncement with new availability information)

    SciTech Connect

    Elsayed, N.M.; Mustafa, M.G.; Mead, J.F.

    1990-11-01

    Vitamin E(vE) is a biological free radical scavenger capable of providing antioxidant protection depending upon its tissue content. In previous studies, we observed that vE increased significantly in rat lungs after oxidant exposure, and we postulated that vE may be mobilized to the lung from other body sites under oxidative stress. To test this hypothesis, we fed Long-Evans rats either a vE-supplemented or a vE-deficient diet, injected them intraperitoneally with carbon 14-labeled vE, and then exposed half of each group to 0.5 ppm ozone (O3) for 5 days. After exposure, we determined vE content and label retention in lungs, liver, kidney, heart, brain, plasma, and white adipose tissue. Tissue vE content of all tissues generally reflected the dietary level, but labeled vE retention in all tissues was inversely related to tissue content, possibly reflecting a saturation of existing vE receptor sites in supplemented rats. Following O3 exposure, lung vE content increased significantly in supplemented rats and decreased in deficient rats, but the decrease was not statistically significant, and vE content remained unchanged in all other tissues of both dietary groups. Retention of 14C-labeled vE increased in all tissues of O3-exposed rats of both dietary groups, except in vE-deficient adipose tissue and vE-supplemented brain, where it decreased, and plasma, where it did not change. The marked increases in lung vE content and labeled vE retention of O3-exposed vE-supplemented rats support our hypothesis that vE may be mobilized to the lung in response to oxidative stress, providing that the vitamin is sufficiently available in other body sites.

  5. Sympathetic Hyperactivity, Increased Tyrosine Hydroxylase and Exaggerated Corpus Cavernosum Relaxations Associated with Oxidative Stress Plays a Major Role in the Penis Dysfunction in Townes Sickle Cell Mouse

    PubMed Central

    Claudino, Mário A.; Calmasini, Fabiano B.; Alexandre, Eduardo C.; Franco-Penteado, Carla; Burnett, Arthur L.; Antunes, Edson; Costa, Fernando F.

    2016-01-01

    Background Sickle cell disease patients display priapism that may progress to erectile dysfunction. However, little is known about the pathophysiological alterations of corpus cavernosum in sickle cell disease. Objective Thus, this study aimed to evaluate the functional and molecular alterations of sympathetic machinery and nitric oxide—cyclic guanosine monophosphate signaling pathway in Townes transgenic sickle cell disease mice. Methods Concentration–response curves to contractile (phenylephrine) and relaxant agents (acetylcholine and sodium nitroprusside) were obtained in corpus cavernosum strips from sickle and C57BL/6 (control) mice. Neurogenic contractions and nitrergic relaxations were obtained using electrical-field stimulation. Measurements of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), phosphodiesterase-5 (PDE5) and α1A-, α1B- and α1D-adrenoceptor mRNA expressions and reactive-oxygen species were performed. Tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expressions in cavernosal tissues were also measured. Results The neurogenic contractions were higher in the sickle cell disease group, in association with elevated tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expression, as well as increased tyrosine hydroxylase mRNA expression. Likewise, phenylephrine-induced contractions were greater in the sickle mice, whereas α1A-, α1B- and α1D-adrenoceptor mRNA expression remained unchanged. Cavernosal relaxations to acetylcholine, sodium nitroprusside and EFS were higher in sickle mice, accompanied by decreased eNOS and nNOS, along with lower PDE5 mRNA expression. An increase of about 40% in reactive-oxygen species generation in corpus cavernosum from sickle mice was also detected. Conclusion Our study shows that decreased nitric oxide bioavailability in erectile tissue due to increased oxidative stress leads to both sympathetic hyperactivity

  6. Chronic cigarette smoking causes hypertension, increased oxidative stress, impaired NO bioavailability, endothelial dysfunction, and cardiac remodeling in mice

    PubMed Central

    Talukder, M. A. Hassan; Johnson, Wesley M.; Varadharaj, Saradhadevi; Lian, Jiarui; Kearns, Patrick N.; El-Mahdy, Mohamed A.; Liu, Xiaoping

    2011-01-01

    Cigarette smoking is a major independent risk factor for cardiovascular disease. While the association between chronic smoking and cardiovascular disease is well established, the underlying mechanisms are incompletely understood, partly due to the lack of adequate in vivo animal models. Here, we report a mouse model of chronic smoking-induced cardiovascular pathology. Male C57BL/6J mice were exposed to whole body mainstream cigarette smoke (CS) using a SCIREQ “InExpose” smoking system (48 min/day, 5 days/wk) for 16 or 32 wk. Age-matched, air-exposed mice served as nonsmoking controls. Blood pressure was measured, and cardiac MRI was performed. In vitro vascular ring and isolated heart experiments were performed to measure vascular reactivity and cardiac function. Blood from control and smoking mice was studied for the nitric oxide (NO) decay rate and reactive oxygen species (ROS) generation. With 32 wk of CS exposure, mice had significantly less body weight gain and markedly higher blood pressure. At 32 wk of CS exposure, ACh-induced vasorelaxation was significantly shifted to the right and downward, left ventricular mass was significantly larger along with an increased heart-to-body weight ratio, in vitro cardiac function tended to be impaired with high afterload, white blood cells had significantly higher ROS generation, and the blood NO decay rate was significantly faster. Thus, smoking led to blunted weight gain, hypertension, endothelial dysfunction, leukocyte activation with ROS generation, decreased NO bioavailability, and mild cardiac hypertrophy in mice that were not otherwise predisposed to disease. This mouse model is a useful tool to enable further elucidation of the molecular and cellular mechanisms of smoking-induced cardiovascular diseases. PMID:21057039

  7. Chronic cigarette smoking causes hypertension, increased oxidative stress, impaired NO bioavailability, endothelial dysfunction, and cardiac remodeling in mice.

    PubMed

    Talukder, M A Hassan; Johnson, Wesley M; Varadharaj, Saradhadevi; Lian, Jiarui; Kearns, Patrick N; El-Mahdy, Mohamed A; Liu, Xiaoping; Zweier, Jay L

    2011-01-01

    Cigarette smoking is a major independent risk factor for cardiovascular disease. While the association between chronic smoking and cardiovascular disease is well established, the underlying mechanisms are incompletely understood, partly due to the lack of adequate in vivo animal models. Here, we report a mouse model of chronic smoking-induced cardiovascular pathology. Male C57BL/6J mice were exposed to whole body mainstream cigarette smoke (CS) using a SCIREQ "InExpose" smoking system (48 min/day, 5 days/wk) for 16 or 32 wk. Age-matched, air-exposed mice served as nonsmoking controls. Blood pressure was measured, and cardiac MRI was performed. In vitro vascular ring and isolated heart experiments were performed to measure vascular reactivity and cardiac function. Blood from control and smoking mice was studied for the nitric oxide (NO) decay rate and reactive oxygen species (ROS) generation. With 32 wk of CS exposure, mice had significantly less body weight gain and markedly higher blood pressure. At 32 wk of CS exposure, ACh-induced vasorelaxation was significantly shifted to the right and downward, left ventricular mass was significantly larger along with an increased heart-to-body weight ratio, in vitro cardiac function tended to be impaired with high afterload, white blood cells had significantly higher ROS generation, and the blood NO decay rate was significantly faster. Thus, smoking led to blunted weight gain, hypertension, endothelial dysfunction, leukocyte activation with ROS generation, decreased NO bioavailability, and mild cardiac hypertrophy in mice that were not otherwise predisposed to disease. This mouse model is a useful tool to enable further elucidation of the molecular and cellular mechanisms of smoking-induced cardiovascular diseases.

  8. Oxidative stress in androgenetic alopecia

    PubMed Central

    Prie, BE; Iosif, L; Tivig, I; Stoian, I; Giurcaneanu, C

    2016-01-01

    Rationale:Androgenetic alopecia is not considered a life threatening disease but can have serious impacts on the patient’s psychosocial life. Genetic, hormonal, and environmental factors are considered responsible for the presence of androgenetic alopecia. Recent literature reports have proved the presence of inflammation and also of oxidative stress at the level of dermal papilla cells of patients with androgenetic alopecia Objective:We have considered of interest to measure the oxidative stress parameters in the blood of patients with androgenetic alopecia Methods and results:27 patients with androgenetic alopecia and 25 age-matched controls were enrolled in the study. Trolox Equivalent Antioxidant Capacity (TEAC), malondialdehyde (MDA) and total thiols levels were measured on plasma samples. Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and also non protein thiols levels together with TEAC activity were determined on erythrocytes samples No statistically significant changes were observed for TEAC erythrocytes, non-protein thiols, GPx and CAT activities. Significantly decreased (p<0.01) SOD activity was found in patients with androgenetic alopecia. For plasma samples decreased TEAC activity (p<0.001), increased MDA levels (p<0.001) and no change in total thiols concentration were found in patients when compared with the controls. Discussions:Decreased total antioxidant activity and increased MDA levels found in plasma samples of patients with androgenetic alopecia are indicators of oxidative stress presence in these patients. Significantly decreased SOD activity but no change in catalase, glutathione peroxidase, non protein thiols level and total antioxidant activity in erythrocytes are elements which suggest the presence of a compensatory mechanism for SOD dysfunction in red blood cells of patients with androgenetic alopecia. Abbreviations: AAG = androgenetic alopecia, MDA = malondialdehyde, SOD = superoxide dismutase

  9. Oxidative stress in androgenetic alopecia.

    PubMed

    Prie, B E; Iosif, L; Tivig, I; Stoian, I; Giurcaneanu, C

    2016-01-01

    Rationale:Androgenetic alopecia is not considered a life threatening disease but can have serious impacts on the patient's psychosocial life. Genetic, hormonal, and environmental factors are considered responsible for the presence of androgenetic alopecia. Recent literature reports have proved the presence of inflammation and also of oxidative stress at the level of dermal papilla cells of patients with androgenetic alopecia Objective:We have considered of interest to measure the oxidative stress parameters in the blood of patients with androgenetic alopecia Methods and results:27 patients with androgenetic alopecia and 25 age-matched controls were enrolled in the study. Trolox Equivalent Antioxidant Capacity (TEAC), malondialdehyde (MDA) and total thiols levels were measured on plasma samples. Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and also non protein thiols levels together with TEAC activity were determined on erythrocytes samples No statistically significant changes were observed for TEAC erythrocytes, non-protein thiols, GPx and CAT activities. Significantly decreased (p<0.01) SOD activity was found in patients with androgenetic alopecia. For plasma samples decreased TEAC activity (p<0.001), increased MDA levels (p<0.001) and no change in total thiols concentration were found in patients when compared with the controls. Discussions:Decreased total antioxidant activity and increased MDA levels found in plasma samples of patients with androgenetic alopecia are indicators of oxidative stress presence in these patients. Significantly decreased SOD activity but no change in catalase, glutathione peroxidase, non protein thiols level and total antioxidant activity in erythrocytes are elements which suggest the presence of a compensatory mechanism for SOD dysfunction in red blood cells of patients with androgenetic alopecia.

  10. Exploring the mechanisms of alcohol-related damage in oral mucosa - is oxidative stress associated with the increase in cell proliferation in rat tongue epithelium?

    PubMed

    Carrard, Vinicius C; Pires, Aline S; Mendez, Marina; Pasquali, Matheus A B; Badauy, Cristiano M; Lauxen, Isabel S; Moreira, José Cláudio F; Sant'ana Filho, Manoel

    2013-02-01

    Alcohol consumption has been related to a cell proliferation increase in oral epithelium but its mechanism remains unclear. The aim of this study was to investigate whether oxidative stress parameters are implicated in the induction of cell proliferation in rat tongue epithelium after different times of chronic alcohol consumption. Cell proliferation was assessed in tongue epithelium using AgNOR (argyrophilic proteins related to active nucleolar organizer regions) quantification. Oxidative stress parameters [lipid peroxidation, protein carbonyls, superoxide dismutase activity and catalase (CAT) activity and immunocontent] and Nrf2 immunocontent were quantified in tongue homogenates. Mean AgNOR numbers (mAgNOR) per nucleus was 2.22 ± 0.30 in ventral tongue epithelium after 120 days of alcohol consumption (vs. 1.87 ± 0.18 for control animals and 1.91 ± 0.23 for animals treated with alcohol for 60 days) indicating cell proliferation increase (p < 0.05, ANOVA followed by Tukey post hoc). Interestingly, 60 days of alcohol consumption induced changes in oxidative stress parameters, but no alteration in cell proliferation. Vitamin E co-treatment was conduced in order to evaluate its possible protective effects. The 120 day Tween + vitamin E + alcohol treatment induced an increase in mAgNORs when compared to the Tween + vitamin E treated group (respectively 2.10 ± 0.30 vs. 1.77 ± 0.11, p < 0.05, ANOVA followed by Tukey post hoc), showing that vitamin E co-treatment had no protective effects. In addition, an inverse association was observed between CAT activity and AgNORs quantity (R = -0.32; p < 0.05, Person's correlation) as well as the possible involvement of Nrf2 in alcohol-related damage. Our findings suggest that the increase in cell proliferation associated with alcohol-related damage has no direct relation