Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

PubMed Central

Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

2010-01-01

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

11th International Conference of Radiation Research

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

NONE

1999-07-18

Topics discussed in the conference included the following: Radiation Physics, Radiation Chemistry and modelling--Radiation physics and dosimetry; Electron transfer in biological media; Radiation chemistry; Biophysical and biochemical modelling; Mechanisms of DNA damage; Assays of DNA damage; Energy deposition in micro volumes; Photo-effects; Special techniques and technologies; Oxidative damage. Molecular and cellular effects-- Photobiology; Cell cycle effects; DNA damage: Strand breaks; DNA damage: Bases; DNA damage Non-targeted; DNA damage: other; Chromosome aberrations: clonal; Chromosomal aberrations: non-clonal; Interactions: Heat/Radiation/Drugs; Biochemical effects; Protein expression; Gene induction; Co-operative effects; ``Bystander'' effects; Oxidative stress effects; Recovery from radiation damage. DNA damage and repair -- DNAmore » repair genes; DNA repair deficient diseases; DNA repair enzymology; Epigenetic effects on repair; and Ataxia and ATM.« less

Cadmium-induced oxidative stress and histological damage in the myocardium. Effects of a soy-based diet

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

Ferramola, Mariana L.; Pérez Díaz, Matías F.F.; Honoré, Stella M.

Cd exposure has been associated to an augmented risk for cardiovascular disease. We investigated the effects of 15 and 100 ppm of Cd on redox status as well as histological changes in the rat heart and the putative protective effect of a soy-based diet. Male Wistar rats were separated into 6 groups and treated during 60 days as follows: groups (1), (2) and (3) were fed a casein-based diet; groups (4), (5) and (6), a soy-based diet; (1) and (4) were given tap water; (2) and (5) tap water containing 15 ppm of Cd{sup 2+}; and (3) and (6) tapmore » water containing 100 ppm of Cd{sup 2+}. Serum lipid peroxides increased and PON-1 activity decreased in group (3). Lipoperoxidation also increased in the heart of all intoxicated groups; however protein oxidation only augmented in (3) and reduced glutathione levels diminished in (2) and (3). Catalase activity increased in groups (3) and (6) while superoxide dismutase activity increased only in (6). Glutathione peroxidase activity decreased in groups (3) and (6). Nrf2 expression was higher in groups (3) and (6), and MTI expression augmented in (3). Histological examination of the heart tissue showed the development of hypertrophic and fusion of cardiomyocytes along with foci of myocardial fiber necrosis. The transmission electron microscopy analysis showed profound ultra-structural damages. No protection against tissue degeneration was observed in animals fed the soy-based diet. Our findings indicate that even though the intake of a soy-based diet is capable of ameliorating Cd induced oxidative stress, it failed in preventing cardiac damage. -- Highlights: ► Cd intoxication produces extracellular and ultrastructural damage in the myocardium. ► The intake of a soy-based diet ameliorated Cd-induced oxidative stress. ► Cd-induced myocardial damage wasn't prevented by the intake of a soy-based diet. ► Cd-induced myocardial degeneration may not be caused by oxidative stress generation. ► Histology evaluation is needed to establish the extent of Cd-induced cardiac damage.« less

Base excision repair: NMR backbone assignments of Escherichia coli formamidopyrimidine-DNA glycosylase

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

Buchko, Garry W.; Wallace, Susan S.; Kennedy, Michael A.

2002-03-01

Oxidative damage is emerging as one of the most important mechanisms responsible for mutagenesis, carcinogenesis, aging, and various diseases (Farr and Kogma, 1991). One of the potential targets for oxidation is cellular DNA. While exposure to exogenous agents, such as ionizing radiation and chemicals, contributes to damaging DNA, the most important oxidative agents are endogenous, such as the reactive free radicals produced during normal oxidative metabolism (Adelman et., 1988). To mitigate the potentially deleterious effects of oxidative DNA damage virtually all aerobic organisms have developed complex repair mechanisms (Petit and Sancar, 1999). One repair mechanism, base excision repair (BER), appearsmore » to be responsible for replacing most oxidative DNA damage (David and Williams, 1998). Formamidopyrimidine-DNA glycosylase (Fpg), a 269-residue metalloprotein with a molecular weight of 30.2 kDa, is a key BER enzyme in prokaryotes (Boiteaux et al., 1987). Substrates recognized and released by Fpg include 7,8-dihydro-8-oxoguanine (8-oxoG), 2,6 diamino-4-hydroxy-5-formamido pyrimidine (Fapy-G), the adenine equivalents 8-oxoA and Fapy-A, 5-hydroxycytosine, 5-hydroxyuracil, B ureidoisobutiric acid, and a-R-hydroxy-B-ureidoisobutiric acid (Freidberg et al., 1995). In vitro Fpg bind double-stranded DNA and performs three catalytic activities: (i) DNA glycosylase, (ii) AP lyase, and (iii) deoxyribophosphodiesterase.« less

Selective enzymatic cleavage and labeling for sensitive capillary electrophoresis laser-induced fluorescence analysis of oxidized DNA bases.

PubMed

Li, Cuiping; Wang, Hailin

2015-08-07

Oxidatively generated DNA damage is considered to be a significant contributing factor to cancer, aging, and age-related human diseases. It is important to detect oxidatively generated DNA damage to understand and clinically diagnosis diseases caused by oxidative damage. In this study, using selective enzymatic cleavage and quantum dot (QD) labeling, we developed a novel capillary electrophoresis-laser induced fluorescence method for the sensitive detection of oxidized DNA bases. First, oxidized DNA bases are recognized and removed by one DNA base excision repair glycosylase, leaving apurinic and apyrimidinic sites (AP sites) at the oxidized positions. The AP sites are further excised by the AP nicking activity of the chosen glycosylase, generating a nucleotide gap with 5'- and 3'- phosphate groups. After dephosphorylation with one alkaline phosphatase, a biotinylated ddNTP is introduced into the nucleotide space within the DNA strand by DNA polymerase I. The biotin-tagged DNA is further labeled with a QD-streptavidin conjugate via non-covalent interactions. The DNA-bound QD is well-separated from excess DNA-unbound QD by highly efficient capillary electrophoresis and is sensitively detected by online coupled laser-induced fluorescence analysis. Using this method, we can assess the trace levels of oxidized DNA bases induced by the Fenton reaction and UV irradiation. Interestingly, the use of the formamidopyrimidine glycosylase (FPG) protein and endonuclease VIII enables the detection of oxidized purine and pyrimidine bases, respectively. Using the synthesized standard DNA, the approach has low limits of detection of 1.1×10(-19)mol in mass and 2.9pM in concentration. Copyright © 2015 Elsevier B.V. All rights reserved.

Base Excision Repair of Oxidative DNA Damage

PubMed Central

David, Sheila S.; O’Shea, Valerie L.; Kundu, Sucharita

2010-01-01

Base excision repair plays an important role in preventing mutations associated with the common product of oxidative damage, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine glycosylases use an intricate series of steps to efficiently search and locate 8-oxoguanine lesions within the multitude of undamaged bases. The importance of prevention of mutations associated with 8-oxoguanine has also been illustrated by direct connections between defects in the BER glycosylase MUTYH and colorectal cancer. In addition, the properties of other guanine oxidation products and the BER glycosylases that remove them are being uncovered. This work is providing surprising and intriguing new insights into the process of base excision repair. PMID:17581577

Toxicity of nano- and micro-sized ZnO particles in human lung epithelial cells

NASA Astrophysics Data System (ADS)

Lin, Weisheng; Xu, Yi; Huang, Chuan-Chin; Ma, Yinfa; Shannon, Katie B.; Chen, Da-Ren; Huang, Yue-Wern

2009-01-01

This is the first comprehensive study to evaluate the cytotoxicity, biochemical mechanisms of toxicity, and oxidative DNA damage caused by exposing human bronchoalveolar carcinoma-derived cells (A549) to 70 and 420 nm ZnO particles. Particles of either size significantly reduced cell viability in a dose- and time-dependent manner within a rather narrow dosage range. Particle mass-based dosimetry and particle-specific surface area-based dosimetry yielded two distinct patterns of cytotoxicity in both 70 and 420 nm ZnO particles. Elevated levels of reactive oxygen species (ROS) resulted in intracellular oxidative stress, lipid peroxidation, cell membrane leakage, and oxidative DNA damage. The protective effect of N-acetylcysteine on ZnO-induced cytotoxicity further implicated oxidative stress in the cytotoxicity. Free Zn2+ and metal impurities were not major contributors of ROS induction as indicated by limited free Zn2+ cytotoxicity, extent of Zn2+ dissociation in the cell culture medium, and inductively-coupled plasma-mass spectrometry metal analysis. We conclude that (1) exposure to both sizes of ZnO particles leads to dose- and time-dependent cytotoxicity reflected in oxidative stress, lipid peroxidation, cell membrane damage, and oxidative DNA damage, (2) ZnO particles exhibit a much steeper dose-response pattern unseen in other metal oxides, and (3) neither free Zn2+ nor metal impurity in the ZnO particle samples is the cause of cytotoxicity.

Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2

PubMed Central

Grindel, Annemarie; Guggenberger, Bianca; Eichberger, Lukas; Pöppelmeyer, Christina; Gschaider, Michaela; Tosevska, Anela; Mare, George; Briskey, David; Brath, Helmut; Wagner, Karl-Heinz

2016-01-01

Background Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration. Methods Female T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals. Results No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group. Conclusion BMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria. PMID:27598300

Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2.

PubMed

Grindel, Annemarie; Guggenberger, Bianca; Eichberger, Lukas; Pöppelmeyer, Christina; Gschaider, Michaela; Tosevska, Anela; Mare, George; Briskey, David; Brath, Helmut; Wagner, Karl-Heinz

2016-01-01

Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration. Female T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals. No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group. BMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.

Sulfur and selenium antioxidants: challenging radical scavenging mechanisms and developing structure-activity relationships based on metal binding.

PubMed

Zimmerman, Matthew T; Bayse, Craig A; Ramoutar, Ria R; Brumaghim, Julia L

2015-04-01

Because sulfur and selenium antioxidants can prevent oxidative damage, numerous animal and clinical trials have investigated the ability of these compounds to prevent the oxidative stress that is an underlying cause of cardiovascular disease, Alzheimer's disease, and cancer, among others. One of the most common sources of oxidative damage is metal-generated hydroxyl radical; however, very little research has focused on determining the metal-binding abilities and structural attributes that affect oxidative damage prevention by sulfur and selenium compounds. In this review, we describe our ongoing investigations into sulfur and selenium antioxidant prevention of iron- and copper-mediated oxidative DNA damage. We determined that many sulfur and selenium compounds inhibit Cu(I)-mediated DNA damage and that DNA damage prevention varies dramatically when Fe(II) is used in place of Cu(I) to generate hydroxyl radical. Oxidation potentials of the sulfur or selenium compounds do not correlate with their ability to prevent DNA damage, highlighting the importance of metal coordination rather than reactive oxygen species scavenging as an antioxidant mechanism. Additional gel electrophoresis, mass spectrometry, and UV-visible studies confirmed sulfur and selenium antioxidant binding to Cu(I) and Fe(II). Ultimately, our studies established that both the hydroxyl-radical-generating metal ion and the chemical environment of the sulfur or selenium significantly affect DNA damage prevention and that metal coordination is an essential mechanism for these antioxidants. Copyright © 2015 Elsevier Inc. All rights reserved.

Hide and seek: How do DNA glycosylases locate oxidatively damaged DNA bases amidst a sea of undamaged bases?

PubMed

Lee, Andrea J; Wallace, Susan S

2017-06-01

The first step of the base excision repair (BER) pathway responsible for removing oxidative DNA damage utilizes DNA glycosylases to find and remove the damaged DNA base. How glycosylases find the damaged base amidst a sea of undamaged bases has long been a question in the BER field. Single molecule total internal reflection fluorescence microscopy (SM TIRFM) experiments have allowed for an exciting look into this search mechanism and have found that DNA glycosylases scan along the DNA backbone in a bidirectional and random fashion. By comparing the search behavior of bacterial glycosylases from different structural families and with varying substrate specificities, it was found that glycosylases search for damage by periodically inserting a wedge residue into the DNA stack as they redundantly search tracks of DNA that are 450-600bp in length. These studies open up a wealth of possibilities for further study in real time of the interactions of DNA glycosylases and other BER enzymes with various DNA substrates. Copyright © 2016 Elsevier Inc. All rights reserved.

Carotenoids, Birdsong and Oxidative Status: Administration of Dietary Lutein Is Associated with an Increase in Song Rate and Circulating Antioxidants (Albumin and Cholesterol) and a Decrease in Oxidative Damage

PubMed Central

Casagrande, Stefania; Pinxten, Rianne; Zaid, Erika; Eens, Marcel

2014-01-01

Despite the appealing hypothesis that carotenoid-based colouration signals oxidative status, evidence supporting the antioxidant function of these pigments is scarce. Recent studies have shown that lutein, the most common carotenoid used by birds, can enhance the expression of non-visual traits, such as birdsong. Nevertheless, the underlying physiological mechanisms remain unclear. In this study we hypothesized that male European starlings (Sturnus vulgaris) fed extra lutein increase their song rate as a consequence of an improved oxidative status. Although birdsong may be especially sensitive to the redox status, this has, to the best of our knowledge, never been tested. Together with the determination of circulating oxidative damage (ROMs, reactive oxygen metabolites), we quantified uric acid, albumin, total proteins, cholesterol, and testosterone, which are physiological parameters potentially sensitive to oxidation and/or related to both carotenoid functions and birdsong expression. We found that the birds fed extra lutein sang more frequently than control birds and showed an increase of albumin and cholesterol together with a decrease of oxidative damage. Moreover, we could show that song rate was associated with high levels of albumin and cholesterol and low levels of oxidative damage, independently from testosterone levels. Our study shows for the first time that song rate honestly signals the oxidative status of males and that dietary lutein is associated with the circulation of albumin and cholesterol in birds, providing a novel insight to the theoretical framework related to the honest signalling of carotenoid-based traits. PMID:25549336

Carotenoids, birdsong and oxidative status: administration of dietary lutein is associated with an increase in song rate and circulating antioxidants (albumin and cholesterol) and a decrease in oxidative damage.

PubMed

Casagrande, Stefania; Pinxten, Rianne; Zaid, Erika; Eens, Marcel

2014-01-01

Despite the appealing hypothesis that carotenoid-based colouration signals oxidative status, evidence supporting the antioxidant function of these pigments is scarce. Recent studies have shown that lutein, the most common carotenoid used by birds, can enhance the expression of non-visual traits, such as birdsong. Nevertheless, the underlying physiological mechanisms remain unclear. In this study we hypothesized that male European starlings (Sturnus vulgaris) fed extra lutein increase their song rate as a consequence of an improved oxidative status. Although birdsong may be especially sensitive to the redox status, this has, to the best of our knowledge, never been tested. Together with the determination of circulating oxidative damage (ROMs, reactive oxygen metabolites), we quantified uric acid, albumin, total proteins, cholesterol, and testosterone, which are physiological parameters potentially sensitive to oxidation and/or related to both carotenoid functions and birdsong expression. We found that the birds fed extra lutein sang more frequently than control birds and showed an increase of albumin and cholesterol together with a decrease of oxidative damage. Moreover, we could show that song rate was associated with high levels of albumin and cholesterol and low levels of oxidative damage, independently from testosterone levels. Our study shows for the first time that song rate honestly signals the oxidative status of males and that dietary lutein is associated with the circulation of albumin and cholesterol in birds, providing a novel insight to the theoretical framework related to the honest signalling of carotenoid-based traits.

Involvement of DNA polymerase beta in repairing oxidative damages induced by antitumor drug adriamycin

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

Liu Shukun; Wu Mei; Zhang Zunzhen, E-mail: zhangzunzhen@163.co

2010-08-01

Adriamycin (ADM) is a widely used antineoplastic drug. However, the increasing cellular resistance has become a serious limitation to ADM clinical application. The most important mechanism related to ADM-induced cell death is oxidative DNA damage mediated by reactive oxygen species (ROS). Base excision repair (BER) is a major pathway in the repair of DNA single strand break (SSB) and oxidized base. In this study, we firstly applied the murine embryo fibroblasts wild-type (pol {beta} +/+) and homozygous pol {beta} null cell (pol {beta} -/-) as a model to investigate ADM DNA-damaging effects and the molecular basis underlying these effects. Here,more » cellular sensitivity to ADM was examined using colorimetric assay and colony forming assay. ADM-induced cellular ROS level and the alteration of superoxide dismutase (SOD) activity were measured by commercial kits. Further, DNA strand break, chromosomal damage and gene mutation were assessed by comet assay, micronucleus test and hprt gene mutation assay, respectively. The results showed that pol {beta} -/- cells were more sensitive to ADM compared with pol {beta} +/+ cells and more severe SSB and chromosomal damage as well as higher hprt gene mutation frequency were observed in pol {beta} -/- cells. ROS level in pol {beta} -/- cells increased along with decreased activity of SOD. These results demonstrated that pol {beta} deficiency could enable ROS accumulation with SOD activity decrease, further elevate oxidative DNA damage, and subsequently result in SSB, chromosome cleavage as well as gene mutation, which may be partly responsible for the cytotoxicity of ADM and the hypersensitivity of pol {beta} -/- cells to ADM. These findings suggested that pol {beta} is vital for repairing oxidative damage induced by ADM.« less

Effects of Military activity and habitat quality on DNA damage and oxidative stress in the largest population of the Federally threatened gopher tortoise.

PubMed

Theodorakis, Christopher W; Adams, S Marshall; Smith, Chandra; Rotter, Jamie; Hay, Ashley; Eslick, Joy

2017-12-01

Department of Defense lands are essential for providing important habitat for threatened, endangered, and at-risk species (TER-S). However, there is little information on the effects of military-related contaminants on TER-S on these lands in field situations. Thus, this study examined genotoxicity and oxidative stress in gopher tortoises (Gopherus polyphemus) on Camp Shelby, MS-the largest known population of this species, which is listed as an "endangered species" in Mississippi and a "threatened species" by the U.S. government. Blood was collected from tortoises at 19 different sites on the base with different levels of habitat quality (high-quality and low-quality habitat) and military activity (high, low, and no military activity). Oxidative stress was quantified as lipid peroxidation and GSSG/GSH ratios, while DNA damage was determined using flow cytometry. Our results suggest that: (1) for tortoises residing in low-quality habitats, oxidative stress and DNA damage increased with increasing military activity, while in high-quality habitats, oxidative stress and DNA damage decreased with increasing military activity; (2) in the absence of military activity, tortoises in high-quality habitat had higher levels of oxidative stress and DNA damage than those in low-quality habitat, and (3) there were interactions between military activity, habitat quality, and landuse in terms of the amount of observable DNA damage and oxidative stress. In particular, on high-quality habitat, tortoises from areas with high levels of military activity had lower levels of oxidative stress and DNA damage biomarkers than on reference sites. This may represent a compensatory or hormetic response. Conversely, on low-quality habitats, the level of oxidative stress and DNA damage was lower on the reference sites. Thus, tortoises on higher-quality habitats may have a greater capacity for compensatory responses. In terms of management implications, it is suggested that low quality habitats should be a higher priority for remediation, and lower priority for conducting military activities.

Nanomaterial induction of oxidative stress in lung epithelial cells and macrophages

NASA Astrophysics Data System (ADS)

Wang, Lin; Pal, Anoop K.; Isaacs, Jacqueline A.; Bello, Dhimiter; Carrier, Rebecca L.

2014-09-01

Oxidative stress in the lung epithelial A549 cells and macrophages J774A.1 due to contact with commercially important nanomaterials [i.e., nano-silver (nAg), nano-alumina (nAl2O3), single-wall carbon nanotubes (CNT), and nano-titanium oxide anatase (nTiO2)] was evaluated. Nanomaterial-induced intracellular oxidative stress was analyzed by both H2DCFDA fluorescein probe and GSH depletion, extracellular oxidative stress was assessed by H2HFF fluorescein probes, and the secretion of chemokine IL-8 by A549 cells due to elevation of cellular oxidative stress was also monitored, in order to provide a comprehensive in vitro study on nanomaterial-induced oxidative stress in lung. In addition, results from this study were also compared with an acellular "ferric reducing ability of serum" (FRAS) assay and a prokaryotic cell-based assay in evaluating oxidative damage caused by the same set of nanomaterials, for comparison purposes. In general, it was found that nanomaterial-induced oxidative stress is highly cell-type dependent. In A549 lung epithelial cells, nAg appeared to induce highest level of oxidative stress and cell death followed by CNT, nTiO2, and nAl2O3. Different biological oxidative damage (BOD) assays' (i.e., H2DCFA, GSH, and IL-8 release) results generally agreed with each other, and the same trends of nanomaterial-induced BOD were also observed in acellular FRAS and prokaryotic E. coli K12-based assay. In macrophage J774A.1 cells, nAl2O3 and nTiO2 appeared to induce highest levels of oxidative stress. These results suggest that epithelial and macrophage cell models may provide complimentary information when conducting cell-based assays to evaluate nanomaterial-induced oxidative damage in lung.

GSTP1 Loss results in accumulation of oxidative DNA base damage and promotes prostate cancer cell survival following exposure to protracted oxidative stress.

PubMed

Mian, Omar Y; Khattab, Mohamed H; Hedayati, Mohammad; Coulter, Jonathan; Abubaker-Sharif, Budri; Schwaninger, Julie M; Veeraswamy, Ravi K; Brooks, James D; Hopkins, Lisa; Shinohara, Debika Biswal; Cornblatt, Brian; Nelson, William G; Yegnasubramanian, Srinivasan; DeWeese, Theodore L

2016-02-01

Epigenetic silencing of glutathione S-transferase π (GSTP1) is a hallmark of transformation from normal prostatic epithelium to adenocarcinoma of the prostate. The functional significance of this loss is incompletely understood. The present study explores the effects of restored GSTP1 expression on glutathione levels, accumulation of oxidative DNA damage, and prostate cancer cell survival following oxidative stress induced by protracted, low dose rate ionizing radiation (LDR). GSTP1 protein expression was stably restored in LNCaP prostate cancer cells. The effect of GSTP1 restoration on protracted LDR-induced oxidative DNA damage was measured by GC-MS quantitation of modified bases. Reduced and oxidized glutathione levels were measured in control and GSTP1 expressing populations. Clonogenic survival studies of GSTP1- transfected LNCaP cells after exposure to protracted LDR were performed. Global gene expression profiling and pathway analysis were performed. GSTP1 expressing cells accumulated less oxidized DNA base damage and exhibited decreased survival compared to control LNCaP-Neo cells following oxidative injury induced by protracted LDR. Restoration of GSTP1 expression resulted in changes in modified glutathione levels that correlated with GSTP1 protein levels in response to protracted LDR-induced oxidative stress. Survival differences were not attributable to depletion of cellular glutathione stores. Gene expression profiling and pathway analysis following GSTP1 restoration suggests this protein plays a key role in regulating prostate cancer cell survival. The ubiquitous epigenetic silencing of GSTP1 in prostate cancer results in enhanced survival and accumulation of potentially promutagenic DNA adducts following exposure of cells to protracted oxidative injury suggesting a protective, anti-neoplastic function of GSTP1. The present work provides mechanistic backing to the tumor suppressor function of GSTP1 and its role in prostate carcinogenesis. © 2015 Wiley Periodicals, Inc.

GSTP1 Loss Results in Accumulation of Oxidative DNA Base Damage and Promotes Prostate Cancer Cell Survival Following Exposure to Protracted Oxidative Stress

PubMed Central

Mian, Omar Y.; Khattab, Mohamed H.; Hedayati, Mohammad; Coulter, Jonathan; Abubaker-Sharif, Budri; Schwaninger, Julie M.; Veeraswamy, Ravi K.; Brooks, James D.; Hopkins, Lisa; Shinohara, Debika Biswal; Cornblatt, Brian; Nelson, William G.; Yegnasubramanian, Srinivasan; DeWeese, Theodore L.

2016-01-01

BACKGROUND Epigenetic silencing of glutathione S-transferase π (GSTP1) is a hallmark of transformation from normal prostatic epithelium to adenocarcinoma of the prostate. The functional significance of this loss is incompletely understood. The present study explores the effects of restored GSTP1 expression on glutathione levels, accumulation of oxidative DNA damage, and prostate cancer cell survival following oxidative stress induced by protracted, low dose rate ionizing radiation (LDR). METHODS GSTP1 protein expression was stably restored in LNCaP prostate cancer cells. The effect of GSTP1 restoration on protracted LDR-induced oxidative DNA damage was measured by GC-MS quantitation of modified bases. Reduced and oxidized glutathione levels were measured in control and GSTP1 expressing populations. Clonogenic survival studies of GSTP1-transfected LNCaP cells after exposure to protracted LDR were performed. Global gene expression profiling and pathway analysis were performed. RESULTS GSTP1 expressing cells accumulated less oxidized DNA base damage and exhibited decreased survival compared to control LNCaP-Neo cells following oxidative injury induced by protracted LDR. Restoration of GSTP1 expression resulted in changes in modified glutathione levels that correlated with GSTP1 protein levels in response to protracted LDR-induced oxidative stress. Survival differences were not attributable to depletion of cellular glutathione stores. Gene expression profiling and pathway analysis following GSTP1 restoration suggests this protein plays a key role in regulating prostate cancer cell survival. CONCLUSIONS The ubiquitous epigenetic silencing of GSTP1 in prostate cancer results in enhanced survival and accumulation of potentially promutagenic DNA adducts following exposure of cells to protracted oxidative injury suggesting a protective, anti-neoplastic function of GSTP1. The present work provides mechanistic backing to the tumor suppressor function of GSTP1 and its role in prostate carcinogenesis. PMID:26447830

Apn1 AP-endonuclease is essential for the repair of oxidatively damaged DNA bases in yeast frataxin-deficient cells.

PubMed

Lefevre, Sophie; Brossas, Caroline; Auchère, Françoise; Boggetto, Nicole; Camadro, Jean-Michel; Santos, Renata

2012-09-15

Frataxin deficiency results in mitochondrial dysfunction and oxidative stress and it is the cause of the hereditary neurodegenerative disease Friedreich ataxia (FA). Here, we present evidence that one of the pleiotropic effects of oxidative stress in frataxin-deficient yeast cells (Δyfh1 mutant) is damage to nuclear DNA and that repair requires the Apn1 AP-endonuclease of the base excision repair pathway. Major phenotypes of Δyfh1 cells are respiratory deficit, disturbed iron homeostasis and sensitivity to oxidants. These phenotypes are weak or absent under anaerobiosis. We show here that exposure of anaerobically grown Δyfh1 cells to oxygen leads to down-regulation of antioxidant defenses, increase in reactive oxygen species, delay in G1- and S-phases of the cell cycle and damage to mitochondrial and nuclear DNA. Nuclear DNA lesions in Δyfh1 cells are primarily caused by oxidized bases and single-strand breaks that can be detected 15-30 min after oxygen exposition. The Apn1 enzyme is essential for the repair of the DNA lesions in Δyfh1 cells. Compared with Δyfh1, the double Δyfh1Δapn1 mutant shows growth impairment, increased mutagenesis and extreme sensitivity to H(2)O(2). On the contrary, overexpression of the APN1 gene in Δyfh1 cells decreases spontaneous and induced mutagenesis. Our results show that frataxin deficiency in yeast cells leads to increased DNA base oxidation and requirement of Apn1 for repair, suggesting that DNA damage and repair could be important features in FA disease progression.

Oxidative DNA Base Damage in MCF-10A Breast Epithelial Cells at Clinically Achievable Concentrations of Doxorubicin

PubMed Central

Gajewski, Ewa; Gaur, Shikha; Akman, Steven A.; Matsumoto, Linda; van Balgooy, Josephus N.A.; Doroshow, James H.

2009-01-01

The cellular metabolism of doxorubicin generates reactive oxygen species with significant potential to damage DNA. Such DNA damage can result in mutations if not adequately repaired by cellular DNA repair pathways. Secondary malignancies have been reported in patients who have received doxorubicin-containing chemotherapeutic regimens; however, the underlying molecular mechanism(s) to explain the development of these tumors remains under active investigation. We have previously demonstrated the presence of DNA bases modified by oxidation in the peripheral blood mononuclear cells of patients with breast cancer following treatment with doxorubicin. In those studies, doxorubicin was administered by continuous infusion over 96 hours to minimize the risk of cardiac toxicity. To evaluate potential mechanisms underlying doxorubicin-induced DNA base oxidation in non-malignant tissues, MCF-10A breast epithelial cells were cultured for 96 hours with the same doxorubicin concentration achieved in vivo (0.1 μM). During doxorubicin exposure, MCF-10A cells underwent growth arrest and apoptosis, developed elevated levels of reactive oxygen species, and demonstrated a time-dependent and significant increase in the levels of 11 oxidized DNA bases, as determined by gas chromatography/mass spectroscopy. Diminished expression of DNA repair enzymes was also observed over the same time course. Thus, clinically achievable concentrations of doxorubicin induce a level of oxidative stress in MCF-10A cells that is capable of oxidizing DNA bases and significantly altering cellular proliferation. PMID:17445777

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

PubMed

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

2007-11-21

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

Redox proteomic evaluation of oxidative modification and recovery in a 3D reconstituted human skin tissue model exposed to UVB.

PubMed

Dyer, J M; Haines, S R; Thomas, A; Wang, W; Walls, R J; Clerens, S; Harland, D P

2017-04-01

Exposure to UV in humans resulting in sunburn triggers a complex series of events that are a mix of immediate and delayed damage mediation and healing. While studies on the effects of UV exposure on DNA damage and repair have been reported, changes in the oxidative modification of skin proteins are poorly understood at the molecular level, despite the important role played by structural proteins in skin tissue, and the effect of the integrity of these proteins on skin appearance and health. Proteomic molecular mapping of oxidation was here applied to try to enhance understanding of skin damage and recovery from oxidative damage and UVB exposure. A redox proteomic-based approach was applied to evaluating skin protein modification when exposed to varying doses of UVB after initial oxidative stress, via tracking changes in protein oxidation during the healing process in vitro using a full-thickness reconstituted human skin tissue model. Bioassays and structural evaluation confirmed that our cultured skin tissues underwent a normal physiological response to UVB exposure. A set of potential skin marker peptides was generated, for use in tracking skin protein oxidative modification. Exposure to UVB after thermal oxidative stress was found to result in higher levels of skin protein oxidation than a non-irradiated control for up to seven days after exposure. Recovery of the skin proteins from oxidative stress, as assessed by the overall protein oxidation levels, was found to be impaired by UVB exposure. Oxidative modification was largely observed in skin structural proteins. Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin proteins, with higher exposure levels leading to increasingly impaired recovery from this damage. This has potential implications for the functional performance of the proteins and inter-related skin health and cosmetic appearance. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Markers of oxidative DNA damage in human interventions with fruit and berries.

PubMed

Freese, Riitta

2006-01-01

Diets rich in fruit and vegetables are associated with a decreased risk of several cancers via numerous possible mechanisms. For example, phytochemicals may decrease oxidative DNA damage and enhance DNA repair. Markers of oxidative DNA damage in human dietary intervention trials used most frequently include oxidized nucleosides such as 7-hydro-8-oxo-2'-deoxyguanosine, which can be analyzed from isolated DNA or urine. Single-cell gel electrophoresis has been widely used to measure baseline or H2O2-induced DNA strand breaks or sites of modified bases sensitive to repair enzymes recognizing oxidized purines or pyrimidines. Recently, markers of DNA repair also have been used. Few controlled human dietary interventions have investigated the specific effects of fruit or berries. There are indications that kiwifruit can decrease H2O2 sensitivity of lymphocyte DNA ex vivo and enhance DNA repair. Carefully controlled studies with flavonoid-rich fruit or berry juices found only few significant differences; less rigorously controlled studies gave more optimistic results. Data on the effects of fruit and berries on DNA damage in humans are scarce and inconclusive; adequately controlled studies with validated markers are needed. Because levels of DNA damage are usually low in young healthy volunteers, groups with an enhanced risk of DNA damage should be studied.

Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes.

PubMed

Zana, Marianna; Szécsényi, Anita; Czibula, Agnes; Bjelik, Annamária; Juhász, Anna; Rimanóczy, Agnes; Szabó, Krisztina; Vetró, Agnes; Szucs, Péter; Várkonyi, Agnes; Pákáski, Magdolna; Boda, Krisztina; Raskó, István; Janka, Zoltán; Kálmán, János

2006-06-30

The aim of the present study was to investigate the oxidative status of lymphocytes from children (n=7) and adults (n=18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults.

A network of enzymes involved in repair of oxidative DNA damage in Neisseria meningitidis

PubMed Central

Li, Yanwen; Pelicic, Vladimir; Freemont, Paul S.; Baldwin, Geoff S.; Tang, Christoph M.

2013-01-01

Although oxidative stress is a key aspect of innate immunity, little is known about how host-restricted pathogens successfully repair DNA damage. Base excision repair (BER) is responsible for correcting nucleobases damaged by oxidative stress, and is essential for bloodstream infection caused by the human pathogen, Neisseria meningitidis. We have characterised meningococcal BER enzymes involved in the recognition and removal of damaged nucleobases, and incision of the DNA backbone. We demonstrate that the bi-functional glycosylase/lyases Nth and MutM share several overlapping activities and functional redundancy. However MutM and other members of the GO system, which deal with 8-oxoG, a common lesion of oxidative damage, are not required for survival of N. meningitidis under oxidative stress. Instead, the mismatch repair pathway provides back-up for the GO system, while the lyase activity of Nth can substitute for the meningococcal AP endonuclease, NApe. Our genetic and biochemical evidence show that DNA repair is achieved through a robust network of enzymes that provides a flexible system of DNA repair. This network is likely to reflect successful adaptation to the human nasopharynx, and might provide a paradigm for DNA repair in other prokaryotes. PMID:22296581

Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli.

PubMed

Moore, Jessica M; Correa, Raul; Rosenberg, Susan M; Hastings, P J

2017-07-01

Bacteria, yeast and human cancer cells possess mechanisms of mutagenesis upregulated by stress responses. Stress-inducible mutagenesis potentially accelerates adaptation, and may provide important models for mutagenesis that drives cancers, host pathogen interactions, antibiotic resistance and possibly much of evolution generally. In Escherichia coli repair of double-strand breaks (DSBs) becomes mutagenic, using low-fidelity DNA polymerases under the control of the SOS DNA-damage response and RpoS general stress response, which upregulate and allow the action of error-prone DNA polymerases IV (DinB), II and V to make mutations during repair. Pol IV is implied to compete with and replace high-fidelity DNA polymerases at the DSB-repair replisome, causing mutagenesis. We report that up-regulated Pol IV is not sufficient for mutagenic break repair (MBR); damaged bases in the DNA are also required, and that in starvation-stressed cells, these are caused by reactive-oxygen species (ROS). First, MBR is reduced by either ROS-scavenging agents or constitutive activation of oxidative-damage responses, both of which reduce cellular ROS levels. The ROS promote MBR other than by causing DSBs, saturating mismatch repair, oxidizing proteins, or inducing the SOS response or the general stress response. We find that ROS drive MBR through oxidized guanines (8-oxo-dG) in DNA, in that overproduction of a glycosylase that removes 8-oxo-dG from DNA prevents MBR. Further, other damaged DNA bases can substitute for 8-oxo-dG because ROS-scavenged cells resume MBR if either DNA pyrimidine dimers or alkylated bases are induced. We hypothesize that damaged bases in DNA pause the replisome and allow the critical switch from high fidelity to error-prone DNA polymerases in the DSB-repair replisome, thus allowing MBR. The data imply that in addition to the indirect stress-response controlled switch to MBR, a direct cis-acting switch to MBR occurs independently of DNA breakage, caused by ROS oxidation of DNA potentially regulated by ROS regulators.

Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli

PubMed Central

Moore, Jessica M.; Correa, Raul; Rosenberg, Susan M.

2017-01-01

Bacteria, yeast and human cancer cells possess mechanisms of mutagenesis upregulated by stress responses. Stress-inducible mutagenesis potentially accelerates adaptation, and may provide important models for mutagenesis that drives cancers, host pathogen interactions, antibiotic resistance and possibly much of evolution generally. In Escherichia coli repair of double-strand breaks (DSBs) becomes mutagenic, using low-fidelity DNA polymerases under the control of the SOS DNA-damage response and RpoS general stress response, which upregulate and allow the action of error-prone DNA polymerases IV (DinB), II and V to make mutations during repair. Pol IV is implied to compete with and replace high-fidelity DNA polymerases at the DSB-repair replisome, causing mutagenesis. We report that up-regulated Pol IV is not sufficient for mutagenic break repair (MBR); damaged bases in the DNA are also required, and that in starvation-stressed cells, these are caused by reactive-oxygen species (ROS). First, MBR is reduced by either ROS-scavenging agents or constitutive activation of oxidative-damage responses, both of which reduce cellular ROS levels. The ROS promote MBR other than by causing DSBs, saturating mismatch repair, oxidizing proteins, or inducing the SOS response or the general stress response. We find that ROS drive MBR through oxidized guanines (8-oxo-dG) in DNA, in that overproduction of a glycosylase that removes 8-oxo-dG from DNA prevents MBR. Further, other damaged DNA bases can substitute for 8-oxo-dG because ROS-scavenged cells resume MBR if either DNA pyrimidine dimers or alkylated bases are induced. We hypothesize that damaged bases in DNA pause the replisome and allow the critical switch from high fidelity to error-prone DNA polymerases in the DSB-repair replisome, thus allowing MBR. The data imply that in addition to the indirect stress-response controlled switch to MBR, a direct cis-acting switch to MBR occurs independently of DNA breakage, caused by ROS oxidation of DNA potentially regulated by ROS regulators. PMID:28727736

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

PubMed

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

2016-12-15

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

Global Protein Oxidation Profiling Suggests Efficient Mitochondrial Proteome Homeostasis During Aging*

PubMed Central

Ramallo Guevara, Carina; Philipp, Oliver; Hamann, Andrea; Werner, Alexandra; Osiewacz, Heinz D.; Rexroth, Sascha; Rögner, Matthias; Poetsch, Ansgar

2016-01-01

The free radical theory of aging is based on the idea that reactive oxygen species (ROS) may lead to the accumulation of age-related protein oxidation. Because themajority of cellular ROS is generated at the respiratory electron transport chain, this study focuses on the mitochondrial proteome of the aging model Podospora anserina as target for ROS-induced damage. To ensure the detection of even low abundant modified peptides, separation by long gradient nLC-ESI-MS/MS and an appropriate statistical workflow for iTRAQ quantification was developed. Artificial protein oxidation was minimized by establishing gel-free sample preparation in the presence of reducing and iron-chelating agents. This first large scale, oxidative modification-centric study for P. anserina allowed the comprehensive quantification of 22 different oxidative amino acid modifications, and notably the quantitative comparison of oxidized and nonoxidized protein species. In total 2341 proteins were quantified. For 746 both protein species (unmodified and oxidatively modified) were detected and the modification sites determined. The data revealed that methionine residues are preferably oxidized. Further prominent identified modifications in decreasing order of occurrence were carbonylation as well as formation of N-formylkynurenine and pyrrolidinone. Interestingly, for the majority of proteins a positive correlation of changes in protein amount and oxidative damage were noticed, and a general decrease in protein amounts at late age. However, it was discovered that few proteins changed in oxidative damage in accordance with former reports. Our data suggest that P. anserina is efficiently capable to counteract ROS-induced protein damage during aging as long as protein de novo synthesis is functioning, ultimately leading to an overall constant relationship between damaged and undamaged protein species. These findings contradict a massive increase in protein oxidation during aging and rather suggest a protein damage homeostasis mechanism even at late age. PMID:26884511

The antileishmanial drug miltefosine (Impavido(®)) causes oxidation of DNA bases, apoptosis, and necrosis in mammalian cells.

PubMed

Castelo Branco, Patrícia Valéria; Soares, Rossy-Eric Pereira; de Jesus, Luís Cláudio Lima; Moreira, Vanessa Ribeiro; Alves, Hugo José; de Castro Belfort, Marta Regina; Silva, Vera Lucia Maciel; Ferreira Pereira, Silma Regina

2016-08-01

Miltefosine was developed to treat skin cancer; further studies showed that the drug also has activity against Leishmania. Miltefosine is the first oral agent for treating leishmaniasis. However, its mechanism of action is not completely understood. We have evaluated the induction of DNA damage by miltefosine. Cytotoxicity and genotoxicity (comet assay) tests were performed on human leukocytes exposed to the drug in vitro. Apoptosis and necrosis were also evaluated. In vivo tests were conducted in Swiss male mice (Mus musculus) treated orally with miltefosine. Oxidation of DNA bases in peripheral blood cells was measured using the comet assay followed by digestion with formamidopyrimidine glycosylase (FPG), which removes oxidized guanine bases. The micronucleus test was performed on bone marrow erythrocytes. Miltefosine caused DNA damage, apoptosis, and necrosis in vitro. Mice treated with miltefosine showed an increase in the DNA damage score, which was further increased following FPG digestion. The micronucleus test was also positive. Copyright © 2016 Elsevier B.V. All rights reserved.

4β-Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells.

PubMed

Tang, Jen-Yang; Huang, Hurng-Wern; Wang, Hui-Ru; Chan, Ya-Ching; Haung, Jo-Wen; Shu, Chih-Wen; Wu, Yang-Chang; Chang, Hsueh-Wei

2018-03-01

Reactive oxygen species (ROS) induction had been previously reported in 4β-hydroxywithanolide (4βHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4βHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4βHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells. 4βHWE decreased cell viability, changed cell morphology and induced ROS generation in oral cancer cells rather than oral normal cells, which were recovered by a free radical scavenger N-acetylcysteine (NAC). For immunofluorescence, 4βHWE also accumulated more of the DSB marker, γH2AX foci, in oral cancer cells than in oral normal cells. For western blotting, DSB signaling proteins such as γH2AX and MRN complex (MRE11, RAD50, and NBS1) were overexpressed in 4βHWE-treated oral cancer cells in different concentrations and treatment time. In the formamidopyrimidine-DNA glycolyase (Fpg)-based comet assay and 8-oxodG-based flow cytometry, the 8-oxodG expressions were higher in 4βHWE-treated oral cancer cells than in oral normal cells. All the 4βHWE-induced DSB and oxidative DNA damage to oral cancer cells were recovered by NAC pretreatment. Taken together, the 4βHWE selectively induced DSB and oxidative DNA damage for the ROS-mediated selective killing of oral cancer cells. © 2017 Wiley Periodicals, Inc.

Walking the Oxidative Stress Tightrope: A Perspective from the Naked Mole-Rat, the Longest-Living Rodent

PubMed Central

Rodriguez, Karl A.; Wywial, Ewa; Perez, Viviana I.; Lambert, Adrian J.; Edrey, Yael H.; Lewis, Kaitlyn N.; Grimes, Kelly; Lindsey, Merry L.; Brand, Martin D.; Buffenstein, Rochelle

2014-01-01

Reactive oxygen species (ROS), by-products of aerobic metabolism, cause oxidative damage to cells and tissue and not surprisingly many theories have arisen to link ROS-induced oxidative stress to aging and health. While studies clearly link ROS to a plethora of divergent diseases, their role in aging is still debatable. Genetic knock-down manipulations of antioxidants alter the levels of accrued oxidative damage, however, the resultant effect of increased oxidative stress on lifespan are equivocal. Similarly the impact of elevating antioxidant levels through transgenic manipulations yield inconsistent effects on longevity. Furthermore, comparative data from a wide range of endotherms with disparate longevity remain inconclusive. Many long-living species such as birds, bats and mole-rats exhibit high-levels of oxidative damage, evident already at young ages. Clearly, neither the amount of ROS per se nor the sensitivity in neutralizing ROS are as important as whether or not the accrued oxidative stress leads to oxidative-damage-linked age-associated diseases. In this review we examine the literature on ROS, its relation to disease and the lessons gleaned from a comparative approach based upon species with widely divergent responses. We specifically focus on the longest lived rodent, the naked mole-rat, which maintains good health and provides novel insights into the paradox of maintaining both an extended healthspan and lifespan despite high oxidative stress from a young age. PMID:21736541

Three job stress models/concepts and oxidative DNA damage in a sample of workers in Japan.

PubMed

Inoue, Akiomi; Kawakami, Norito; Ishizaki, Masao; Tabata, Masaji; Tsuchiya, Masao; Akiyama, Miki; Kitazume, Akiko; Kuroda, Mitsuyo; Shimazu, Akihito

2009-04-01

Three job stress models/concepts (the job demands-control [DC] model, the effort-reward imbalance [ERI] model, and organizational justice) have been linked to coronary heart disease (CHD) at work. In recent years, oxidative DNA damage has been identified as a new risk factor for CHD. However, evidence for the association between these job stressors and oxidative DNA damage is limited. The present cross-sectional study investigated the association between these job stress models/concepts and oxidative DNA damage as a possible mediator of the adverse health effects of job stress. A total of 166 male and 51 female workers of a manufacturing factory in Japan were surveyed using a mailed questionnaire regarding job stressors and demographic, occupational, and lifestyle variables. Urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were also measured. In male subjects, the urinary concentrations of 8-OHdG were significantly higher among the group with lower interactional justice, one of the two components of organizational justice; however, no association was observed with the DC model or the ERI model. In female subjects, high job demands/control ratio was significantly and positively associated with the urinary concentrations of 8-OHdG. Interactional justice among male workers and the DC model-based strain among female workers may be associated with increased urinary concentrations of 8-OHdG which possibly reflects oxidative DNA damage.

Development and evaluation of yeast-based GFP and luciferase reporter assays for chemical-induced genotoxicity and oxidative damage.

PubMed

Suzuki, Hajime; Sakabe, Takahiro; Hirose, Yuu; Eki, Toshihiko

2017-01-01

We aimed to develop the bioassays for genotixicity and/or oxidative damage using the recombinant yeast. A genotoxicity assay was developed using recombinant Saccharomyces cerevisiae strain BY4741 with a green fluorescent protein (GFP) reporter plasmid, driven by the DNA damage-responsive RNR3 promoter. Enhanced fluorescence induction was observed in DNA repair-deficient strains treated with methyl methanesulfonate, but not with hydrogen peroxide. A GFP reporter yeast strain driven by the oxidative stress-responsive TRX2 promoter was newly developed to assess oxidative damage, but fluorescence was poorly induced by oxidants. In place of GFP, yeast strains with luciferase gene reporter plasmids (luc2 and luc2CP, encoding stable and unstable luciferase, respectively) were prepared. Transient induction of luciferase activity was clearly detected only in a TRX2 promoter-driven luc2CP reporter strain within 90 min of oxidant exposure. However, luciferase was strongly induced by hydroxyurea in the RNR3 promoter-driven luc2 and GFP reporter strains over 8 h after the exposure, suggesting that the RNR3 promoter is continuously upregulated by DNA damage, whereas the TRX2 promoter is transiently activated by oxidative agents. Luciferase activity levels were also increased in a TRX2-promoter-driven luc2CP reporter strain treated with tert-butyl hydroperoxide and menadione and weakly induced with diamide and diethyl maleate. Weakly enhanced luciferase activity induction was detected in the sod1Δ, sod2Δ, and rad27Δ strains treated with hydrogen peroxide compared with that in the wild-type strain. In conclusion, tests using GFP and stable luciferase reporters are useful for genotoxicity, and oxidative damage can be clearly detected by assay with an unstable luciferase reporter.

Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide

DOE PAGES

Freudenthal, Bret D.; Beard, William A.; Perera, Lalith; ...

2014-11-17

Oxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2’-deoxyguanosine found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate E. coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerase discriminates between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities,more » nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine (Cy) and 8-oxodGTP(syn) utilizes its Hoogsteen edge to base pair with adenine (Ad). Here in this paper we utilized time-lapse crystallography to follow 8-oxo-dGTP insertion opposite Ad or Cy with human DNA pol β, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxodGTP utilizes charge modulation during insertion that can lead to a blocked DNA repair intermediate.« less

Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide

NASA Astrophysics Data System (ADS)

Freudenthal, Bret D.; Beard, William A.; Perera, Lalith; Shock, David D.; Kim, Taejin; Schlick, Tamar; Wilson, Samuel H.

2015-01-01

Oxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2'-deoxyguanosine, which is found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate Escherichia coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerases discriminate between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with adenine. Here we use time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human pol β, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen-bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can lead to a blocked DNA repair intermediate.

5-s-Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons.

PubMed

Spencer, Jeremy P E; Whiteman, Matthew; Jenner, Peter; Halliwell, Barry

2002-04-01

A decrease in reduced glutathione levels in dopamine containing nigral cells in Parkinson's disease may result from the formation of cysteinyl-adducts of catecholamines, which in turn exert toxicity on nigral cells. We show that exposure of neurons (CSM 14.1) to 5-S-cysteinyl conjugates of dopamine, L-DOPA, DOPAC or DHMA causes neuronal damage, increases in oxidative DNA base modification and an elevation of caspase-3 activity in cells. Damage to neurons was apparent 12-48 h of post-exposure and there were increases in caspase-3 activity in neurons after 6 h. These changes were paralleled by large increases in pyrimidine and purine base oxidation products, such as 8-OH-guanine suggesting that 5-S-cysteinyl conjugates of catecholamines are capable of diffusing into cells and stimulating the formation of reactive oxygen species (ROS), which may then lead to a mechanism of cell damage involving caspase-3. Indeed, intracellular ROS were observed to rise sharply on exposure to the conjugates. These results suggest one mechanism by which oxidative stress may occur in the substantia nigra in Parkinson's disease.

Determinants of spontaneous mutation in the bacterium Escherichia coli as revealed by whole-genome sequencing

PubMed Central

Foster, Patricia L.; Lee, Heewook; Popodi, Ellen; Townes, Jesse P.; Tang, Haixu

2015-01-01

A complete understanding of evolutionary processes requires that factors determining spontaneous mutation rates and spectra be identified and characterized. Using mutation accumulation followed by whole-genome sequencing, we found that the mutation rates of three widely diverged commensal Escherichia coli strains differ only by about 50%, suggesting that a rate of 1–2 × 10−3 mutations per generation per genome is common for this bacterium. Four major forces are postulated to contribute to spontaneous mutations: intrinsic DNA polymerase errors, endogenously induced DNA damage, DNA damage caused by exogenous agents, and the activities of error-prone polymerases. To determine the relative importance of these factors, we studied 11 strains, each defective for a major DNA repair pathway. The striking result was that only loss of the ability to prevent or repair oxidative DNA damage significantly impacted mutation rates or spectra. These results suggest that, with the exception of oxidative damage, endogenously induced DNA damage does not perturb the overall accuracy of DNA replication in normally growing cells and that repair pathways may exist primarily to defend against exogenously induced DNA damage. The thousands of mutations caused by oxidative damage recovered across the entire genome revealed strong local-sequence biases of these mutations. Specifically, we found that the identity of the 3′ base can affect the mutability of a purine by oxidative damage by as much as eightfold. PMID:26460006

Direct participation of DNA in the formation of singlet oxygen and base damage under UVA irradiation.

PubMed

Yagura, Teiti; Schuch, André Passaglia; Garcia, Camila Carrião Machado; Rocha, Clarissa Ribeiro Reily; Moreno, Natália Cestari; Angeli, José Pedro Friedmann; Mendes, Davi; Severino, Divinomar; Bianchini Sanchez, Angelica; Di Mascio, Paolo; de Medeiros, Marisa Helena Gennari; Menck, Carlos Frederico Martins

2017-07-01

UVA light is hardly absorbed by the DNA molecule, but recent works point to a direct mechanism of DNA lesion by these wavelengths. UVA light also excite endogenous chromophores, which causes DNA damage through ROS. In this study, DNA samples were irradiated with UVA light in different conditions to investigate possible mechanisms involved in the induction of DNA damage. The different types of DNA lesions formed after irradiation were determined through the use of endonucleases, which recognize and cleave sites containing oxidized bases and cyclobutane pyrimidine dimers (CPDs), as well as through antibody recognition. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxodG) was also studied in more detail using electrochemical detection. The results show that high NaCl concentration and concentrated DNA are capable of reducing the induction of CPDs. Moreover, concerning damage caused by oxidative stress, the presence of sodium azide and metal chelators reduce their induction, while deuterated water increases the amounts of oxidized bases, confirming the involvement of singlet oxygen in the generation of these lesions. Curiously, however, high concentrations of DNA also enhanced the formation of oxidized bases, in a reaction that paralleled the increase in the formation of singlet oxygen in the solution. This was interpreted as being due to an intrinsic photosensitization mechanism, depending directly on the DNA molecule to absorb UVA and generate singlet oxygen. Therefore, the DNA molecule itself may act as a chromophore for UVA light, locally producing a damaging agent, which may lead to even greater concerns about the deleterious impact of sunlight. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxidatively-induced DNA damage and base excision repair in euthymic patients with bipolar disorder.

PubMed

Ceylan, Deniz; Tuna, Gamze; Kirkali, Güldal; Tunca, Zeliha; Can, Güneş; Arat, Hidayet Ece; Kant, Melis; Dizdaroglu, Miral; Özerdem, Ayşegül

2018-05-01

Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51). The expression of DNA repair enzymes OGG1 and NEIL1 were measured using quantitative real-time polymerase chain reaction. The levels of malondialdehyde were measured using high performance liquid chromatography. Seven DNA base lesions in DNA of leukocytes of patients and healthy individuals were identified and quantified. Three of them had significantly elevated levels in bipolar patients when compared to healthy individuals. No elevation of lipid peroxidation marker malondialdehyde was observed. The level of OGG1 expression was significantly reduced in bipolar patients compared to healthy individuals, whereas the two groups exhibited similar levels of NEIL1 expression. Our results suggest that oxidatively-induced DNA damage occurs and base excision repair capacity may be decreased in bipolar patients when compared to healthy individuals. Measurement of oxidatively-induced DNA base lesions and the expression of DNA repair enzymes may be of great importance for large scale basic research and clinical studies of bipolar disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases

PubMed Central

Mitra, Joy; Guerrero, Erika N.; Hegde, Pavana M.; Wang, Haibo; Boldogh, Istvan; Rao, Kosagi Sharaf; Mitra, Sankar; Hegde, Muralidhar L.

2014-01-01

The primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases. PMID:25036887

Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart.

PubMed

Gredilla, R; Barja, G; López-Torres, M

2001-10-01

Oxygen radicals of mitochondrial origin are involved in oxidative damage. In order to analyze the possible relationship between metabolic rate, oxidative stress and oxidative damage, OF1 female mice were rendered hyper- and hypothyroid by chronic administration of 0.0012% L-thyroxine (T4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid peroxidation in the heart, although the endogenous levels of lipid peroxidation were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochondrial DNA was greater than that to genomic DNA. Hyperthyroidism decreased oxidative damage to genomic DNA. Hypothyroidism did not modify oxidative damage in the lipid fraction but significantly decreased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to lipids and DNA, and cellular redox potential in the mouse heart. A higher oxidative stress in the hyperthyroid group is presumably neutralized in the case of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxidative damage in the different cell compartments.

The role of the RB tumour suppressor pathway in oxidative stress responses in the haematopoietic system

PubMed Central

Macleod, Kay F.

2010-01-01

Exposure to pro-oxidants and defects in the repair of oxidative base damage are associated with disease and ageing and also contribute to the development of anaemia, bone marrow failure and haematopoietic malignancies. This Review assesses emerging data indicative of a specific role for the RB tumour suppressor pathway in the response of the haematopoietic system to oxidative stress. This is mediated through signalling pathways that involve DNA damage sensors, forkhead box O (Foxo) transcription factors and p38 mitogen-activated protein kinases and has downstream consequences for cell cycle progression, antioxidant capacity, mitochondrial mass and cellular metabolism. PMID:18800074

Base Excision Repair and Lesion-Dependent Subpathways for Repair of Oxidative DNA Damage

PubMed Central

Svilar, David; Goellner, Eva M.; Almeida, Karen H.

2011-01-01

Abstract Nuclear and mitochondrial genomes are under continuous assault by a combination of environmentally and endogenously derived reactive oxygen species, inducing the formation and accumulation of mutagenic, toxic, and/or genome-destabilizing DNA lesions. Failure to resolve these lesions through one or more DNA-repair processes is associated with genome instability, mitochondrial dysfunction, neurodegeneration, inflammation, aging, and cancer, emphasizing the importance of characterizing the pathways and proteins involved in the repair of oxidative DNA damage. This review focuses on the repair of oxidative damage–induced lesions in nuclear and mitochondrial DNA mediated by the base excision repair (BER) pathway in mammalian cells. We discuss the multiple BER subpathways that are initiated by one of 11 different DNA glycosylases of three subtypes: (a) bifunctional with an associated β-lyase activity; (b) monofunctional; and (c) bifunctional with an associated β,δ-lyase activity. These three subtypes of DNA glycosylases all initiate BER but yield different chemical intermediates and hence different BER complexes to complete repair. Additionally, we briefly summarize alternate repair events mediated by BER proteins and the role of BER in the repair of mitochondrial DNA damage induced by ROS. Finally, we discuss the relation of BER and oxidative DNA damage in the onset of human disease. Antioxid. Redox Signal. 14, 2491–2507. PMID:20649466

Effects of dietary almond- and olive oil-based docosahexaenoic acid- and vitamin E-enriched beverage supplementation on athletic performance and oxidative stress markers.

PubMed

Capó, X; Martorell, M; Busquets-Cortés, C; Sureda, A; Riera, J; Drobnic, F; Tur, J A; Pons, A

2016-12-07

Functional beverages based on almonds and olive oil and enriched with α-tocopherol and docosahexaenoic acid (DHA) could be useful in modulating oxidative stress and enhancing physical performance in sportsmen. The aim of this work was to evaluate the effects of supplementation with functional beverages on physical performance, plasma and erythrocyte fatty acids' and polyphenol handling, oxidative and nitrative damage, and antioxidant and mitochondrial gene expression in young and senior athletes. Athletes performed maximal exercise tests before and after one month of dietary supplementation and blood samples were taken immediately before and one hour after each test. The beverages did not alter performance parameters during maximal exercise. Supplementation increased polyunsaturated and reduced saturated plasma fatty acids while increasing the DHA erythrocyte content; it maintained basal plasma and blood polyphenol levels, but increased the blood cell polyphenol concentration in senior athletes. Supplementation protects against oxidative damage although it enhances nitrative damage in young athletes. The beverages enhance the gene expression of antioxidant enzymes in peripheral blood mononuclear cells after exercise in young athletes.

A new oxidation based technique for artifact free TEM specimen preparation of nuclear graphite

NASA Astrophysics Data System (ADS)

Johns, Steve; Shin, Wontak; Kane, Joshua J.; Windes, William E.; Ubic, Rick; Karthik, Chinnathambi

2018-07-01

Graphite is a key component in designs of current and future nuclear reactors whose in-service lifetimes are dependent upon the mechanical performance of the graphite. Irradiation damage from fast neutrons creates lattice defects which have a dynamic effect on the microstructure and mechanical properties of graphite. Transmission electron microscopy (TEM) can offer real-time monitoring of the dynamic atomic-level response of graphite subjected to irradiation; however, conventional TEM specimen-preparation techniques, such as argon ion milling itself, damage the graphite specimen and introduce lattice defects. It is impossible to distinguish these defects from the ones created by electron or neutron irradiation. To ensure that TEM specimens are artifact-free, a new oxidation-based technique has been developed. Bulk nuclear grades of graphite (IG-110 and NBG-18) and highly oriented pyrolytic graphite (HOPG) were initially mechanically thinned to ∼60 μm. Discs 3 mm in diameter were then oxidized at temperatures between 575 °C and 625 °C in oxidizing gasses using a new jet-polisher-like set-up in order to achieve optimal oxidation conditions to create self-supporting electron-transparent TEM specimens. The quality of these oxidized specimens were established using optical and electron microscopy. Samples oxidized at 575 °C exhibited large areas of electron transparency and the corresponding lattice imaging showed no apparent damage to the graphite lattice.

A new oxidation based technique for artifact free TEM specimen preparation of nuclear graphite

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

Johns, Steve; Shin, Wontak; Kane, Joshua J.

Graphite is a key component in designs of current and future nuclear reactors whose in-service lifetimes are dependent upon the mechanical performance of the graphite. Irradiation damage from fast neutrons creates lattice defects which have a dynamic effect on the microstructure and mechanical properties of graphite. Transmission electron microscopy (TEM) can offer real-time monitoring of the dynamic atomic-level response of graphite subjected to irradiation; however, conventional TEM specimen-preparation techniques, such as argon ion milling itself, damage the graphite specimen and introduce lattice defects. It is impossible to distinguish these defects from the ones created by electron or neutron irradiation. Thus,tomore » ensure that TEM specimens are artifact-free, a new oxidation-based technique has been developed. Bulk nuclear grades of graphite (IG-110 and NBG-18) and highly oriented pyrolytic graphite (HOPG) were initially mechanically thinned to ~60μm. Discs 3mm in diameter were then oxidized at temperatures between 575°C and 625°C in oxidizing gasses using a new jet-polisher-like set-up in order to achieve optimal oxidation conditions to create self-supporting electron-transparent TEM specimens. The quality of these oxidized specimens were established using optical and electron microscopy. Samples oxidized at 575°C exhibited large areas of electron transparency and the corresponding lattice imaging showed no apparent damage to the graphite lattice.« less

A new oxidation based technique for artifact free TEM specimen preparation of nuclear graphite

DOE PAGES

Johns, Steve; Shin, Wontak; Kane, Joshua J.; ...

2018-04-03

Graphite is a key component in designs of current and future nuclear reactors whose in-service lifetimes are dependent upon the mechanical performance of the graphite. Irradiation damage from fast neutrons creates lattice defects which have a dynamic effect on the microstructure and mechanical properties of graphite. Transmission electron microscopy (TEM) can offer real-time monitoring of the dynamic atomic-level response of graphite subjected to irradiation; however, conventional TEM specimen-preparation techniques, such as argon ion milling itself, damage the graphite specimen and introduce lattice defects. It is impossible to distinguish these defects from the ones created by electron or neutron irradiation. Thus,tomore » ensure that TEM specimens are artifact-free, a new oxidation-based technique has been developed. Bulk nuclear grades of graphite (IG-110 and NBG-18) and highly oriented pyrolytic graphite (HOPG) were initially mechanically thinned to ~60μm. Discs 3mm in diameter were then oxidized at temperatures between 575°C and 625°C in oxidizing gasses using a new jet-polisher-like set-up in order to achieve optimal oxidation conditions to create self-supporting electron-transparent TEM specimens. The quality of these oxidized specimens were established using optical and electron microscopy. Samples oxidized at 575°C exhibited large areas of electron transparency and the corresponding lattice imaging showed no apparent damage to the graphite lattice.« less

NEIL2 Protects against Oxidative DNA Damage Induced by Sidestream Smoke in Human Cells

PubMed Central

Sarker, Altaf H.; Chatterjee, Arpita; Williams, Monique; Lin, Sabrina; Havel, Christopher; Jacob III, Peyton; Boldogh, Istvan; Hazra, Tapas K.; Talbot, Prudence; Hang, Bo

2014-01-01

Secondhand smoke (SHS) is a confirmed lung carcinogen that introduces thousands of toxic chemicals into the lungs. SHS contains chemicals that have been implicated in causing oxidative DNA damage in the airway epithelium. Although DNA repair is considered a key defensive mechanism against various environmental attacks, such as cigarette smoking, the associations of individual repair enzymes with susceptibility to lung cancer are largely unknown. This study investigated the role of NEIL2, a DNA glycosylase excising oxidative base lesions, in human lung cells treated with sidestream smoke (SSS), the main component of SHS. To do so, we generated NEIL2 knockdown cells using siRNA-technology and exposed them to SSS-laden medium. Representative SSS chemical compounds in the medium were analyzed by mass spectrometry. An increased production of reactive oxygen species (ROS) in SSS-exposed cells was detected through the fluorescent detection and the induction of HIF-1α. The long amplicon–quantitative PCR (LA-QPCR) assay detected significant dose-dependent increases of oxidative DNA damage in the HPRT gene of cultured human pulmonary fibroblasts (hPF) and BEAS-2B epithelial cells exposed to SSS for 24 h. These data suggest that SSS exposure increased oxidative stress, which could contribute to SSS-mediated toxicity. siRNA knockdown of NEIL2 in hPF and HEK 293 cells exposed to SSS for 24 h resulted in significantly more oxidative DNA damage in HPRT and POLB than in cells with control siRNA. Taken together, our data strongly suggest that decreased repair of oxidative DNA base lesions due to an impaired NEIL2 expression in non-smokers exposed to SSS would lead to accumulation of mutations in genomic DNA of lung cells over time, thus contributing to the onset of SSS-induced lung cancer. PMID:24595271

Glycosylases utilize ``stop and go'' motion to locate DNA damage

NASA Astrophysics Data System (ADS)

Nelson, Shane

2015-03-01

Oxidative damage to DNA results in alterations that are mutagenic or even cytotoxic. Base excision repair is a mechanism that functions to identify and correct these lesions, and is present in organisms ranging from bacteria to humans. DNA glycosylases are the first enzymes in this pathway and function to locate and remove oxidatively damaged bases, and do so utilizing only thermal energy. However, the question remains of how these enzymes locate and recognize a damaged base among millions of undamaged bases. Utilizing fluorescence video microscopy with high spatial and temporal resolution, we have observed a number of different fluorescently labeled glycosylases (including bacterial FPG, NEI, and NTH as well as mammalian MutyH and OGG). These enzymes diffuse along DNA tightropes at approximately 0.01 +/- 0.005 μm2/s with binding lifetimes ranging from one second to several minutes. Chemically induced damage to the DNA substrate causes a ~ 50% reduction in diffusion coefficients and a ~ 400% increase in binding lifetimes, while mutation of the key ``wedge residue'' - which has been shown to be responsible for damage detection - results in a 200% increase in the diffusion coefficient. Utilizing a sliding window approach to measure diffusion coefficients within individual trajectories, we observe that distributions of diffusion coefficients are bimodal, consistent with periods of diffusive motion interspersed with immobile periods. Utilizing a unique chemo-mechanical simulation approach, we demonstrate that the motion of these glycosylases can be explained as free diffusion along the helical pitch of the DNA, punctuated with two different types of pauses: 1) rapid, short-lived pauses as the enzyme rapidly probes DNA bases to interrogate for damage and, 2) less frequent, longer lived pauses that reflect the enzyme bound to and catalytically removing a damaged base. These simulations also indicate that the wedge residue is critical for interrogation and recognition of damage, and thus enzymes missing this residue diffuse faster. Similarly, chemically induced damage increases the frequency with which the enzymes encounter damaged bases, resulting in slower diffusion.

Using digital flow cytometry to assess the degradation of three cyanobacteria species after oxidation processes.

PubMed

Wert, Eric C; Dong, Mei Mei; Rosario-Ortiz, Fernando L

2013-07-01

Depending on drinking water treatment conditions, oxidation processes may result in the degradation of cyanobacteria cells causing the release of toxic metabolites (microcystin), odorous metabolites (MIB, geosmin), or disinfection byproduct precursors. In this study, a digital flow cytometer (FlowCAM(®)) in combination with chlorophyll-a analysis was used to evaluate the ability of ozone, chlorine, chlorine dioxide, and chloramine to damage or lyse cyanobacteria cells added to Colorado River water. Microcystis aeruginosa (MA), Oscillatoria sp. (OSC) and Lyngbya sp. (LYN) were selected for the study due to their occurrence in surface water supplies, metabolite production, and morphology. Results showed that cell damage was observed without complete lysis or fragmentation of the cell membrane under many of the conditions tested. During ozone and chlorine experiments, the unicellular MA was more susceptible to oxidation than the filamentous OSC and LYN. Rate constants were developed based on the loss of chlorophyll-a and oxidant exposure, which showed the oxidants degraded MA, OSC, and LYN according to the order of ozone > chlorine ~ chlorine dioxide > chloramine. Digital and binary images taken by the digital flow cytometer provided qualitative insight regarding cell damage. When applying this information, drinking water utilities can better understand the risk of cell damage or lysis during oxidation processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

FIBER OPTIC BIOSENSOR FOR DNA DAMAGE

EPA Science Inventory

This paper describes a fiber optic biosensor for the rapid and sensitive detection of radiation-induced or chemically-induced oxidative DNA damage. The assay is based on the hybridization and temperature-induced dissociation (melting curves) of synthetic oligonucleotides. The...

Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage.

PubMed

Moat, S J; Hill, M H; McDowell, I F W; Pullin, C H; Ashfield-Watt, P A L; Clark, Z E; Whiting, J M; Newcombe, R G; Lewis, M J; Powers, H J

2003-03-01

Various mechanisms have been proposed to explain the association between plasma total homocysteine (tHcy) and risk of cardiovascular disease, including oxidative activity of homocysteine. To explore the putative role of reactive oxygen species in the association between plasma tHcy and risk of cardiovascular disease in healthy individuals. A double-blind, placebo-controlled crossover intervention to increase folate intake through diet (increased consumption of folate-rich foods) and supplement (400 micro g folic acid) was carried out in 126 healthy men and women. Measurements were made of antioxidant activity in red blood cells and plasma, and products of oxidant damage in plasma. Diet and supplement-based interventions led to an increase in measures of folate status and a reduction in plasma tHcy. This was not associated with any significant change in measures of antioxidant activity (plasma and red blood cell glutathione peroxidase activity and red blood cell superoxide dismutase activity) or oxidant damage (plasma malondialdehyde), although an improvement in plasma total antioxidant capacity just failed to reach significance. In healthy individuals lowering plasma tHcy does not have any functional implications regarding oxidative damage.

Base excision repair, the redox environment and therapeutic implications.

PubMed

Storr, S J; Woolston, C M; Martin, S G

2012-01-01

Control of redox homeostasis is crucial for a number of cellular processes with deregulation leading to a number of serious consequences including oxidative damage such induction of DNA base lesions. The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. Pharmacological inhibition of BER is becoming an increasingly active area of research with the emergence of PARP inhibitors in cancer therapy. The redox status of the cell is modulated by a number of systems, including a large number of anti-oxidant enzymes who function in the control of superoxide and hydrogen peroxide, and ultimately in the release of the damaging hydroxyl radical. Here we provide an overview of reactive oxygen species (ROS) production and its modulation by antioxidant enzymes. The review also discusses the effect of ROS on the BER pathway, particularly in relation to cancer. Finally, as the modulation of the redox environment is of interest in cancer therapy, with certain agents having the potential to reverse chemo- and radiotherapy resistance or treat therapy related toxicity, we discuss redox modulating agents currently under development.

Duplex Interrogation by a Direct DNA Repair Protein in Search of Base Damage

PubMed Central

Yi, Chengqi; Chen, Baoen; Qi, Bo; Zhang, Wen; Jia, Guifang; Zhang, Liang; Li, Charles J.; Dinner, Aaron R.; Yang, Cai-Guang; He, Chuan

2012-01-01

ALKBH2 is a direct DNA repair dioxygenase guarding mammalian genome against N1-methyladenine, N3-methylcytosine, and 1,N6-ethenoadenine damage. A prerequisite for repair is to identify these lesions in the genome. Here we present crystal structures of ALKBH2 bound to different duplex DNAs. Together with computational and biochemical analyses, our results suggest that DNA interrogation by ALKBH2 displays two novel features: i) ALKBH2 probes base-pair stability and detects base pairs with reduced stability; ii) ALKBH2 does not have nor need a “damage-checking site”, which is critical for preventing spurious base-cleavage for several glycosylases. The demethylation mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed to normal bases, and that a flipped, non-substrate base remains intact in the active site. Overall, the combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly. PMID:22659876

Biomarkers of oxidative damage and antioxidant defense capacity in Caiman latirostris blood.

PubMed

Poletta, Gisela L; Simoniello, María Fernanda; Mudry, Marta D

2016-01-01

Several xenobiotics, and among them pesticides, can produce oxidative stress, providing a mechanistic basis for their observed toxicity. Chronic oxidative stress induces deleterious modifications to DNA, lipids and proteins that are used as effective biomarkers to study pollutant-mediated oxidative stress. No previous report existed on the application of oxidative damage and antioxidant defense biomarkers in Caiman latirostris blood, while few studies reported in other crocodilians were done in organs or muscles of dead animals. The aim of this study was to characterize a new set of oxidative stress biomarkers in C. latirostris blood, through the modification of conventional techniques: 1) damage to lipids by thiobarbituric acid reactive substances (TBARS), 2) damage to DNA by comet assay modified with the enzymes FPG and Endo III, and 3) antioxidant defenses: catalase, superoxide dismutase and glutathione; in order to apply them in future biomonitoring studies. We successfully adapted standard procedures for CAT, SOD, GSH and TBARS determination in C. latirostris blood. Calibration curves for FPG and Endo III showed that the three dilutions tested were appropriate to conduct the modified comet assay for the detection of oxidized bases in C. latirostris erythrocytes. One hour of incubation allowed a complete repair of the damage generated. The incorporation of these biomarkers in biomonitoring studies of caiman populations exposed to xenobiotics is highly important considering that this species has recovered from a serious endangered state through the implementation of sustainable use programs in Argentina, and represents nowadays a relevant economic resource for many human communities. Copyright © 2015 Elsevier Inc. All rights reserved.

The in vivo antioxidant action and the reduction of oxidative stress by boysenberry extract is dependent on base diet constituents in rats.

PubMed

Barnett, Laura E; Broomfield, Anne M; Hendriks, Wouter H; Hunt, Martin B; McGhie, Tony K

2007-06-01

Dietary antioxidants are often defined by in vitro measures of antioxidant activity. Such measures are valid indicators of the antioxidant potential, but provide little evidence of activity as a dietary antioxidant. This study was undertaken to assess the in vivo antioxidant efficacy of a berry fruit extract by measuring biomarkers of oxidative damage to protein (carbonyls), lipids (malondialdehyde), and DNA (8-oxo-2'-deoxyguanosine urinary excretion) and plasma antioxidant status (antioxidant capacity, vitamin E) in rats when fed basal diets containing fish and soybean oils, which are likely to generate different levels of oxidative stress. Boysenberry (Rubus loganbaccus x baileyanus Britt) extract was used as the dietary antioxidant. The basal diets (chow, synthetic/soybean oil, or synthetic/fish oil) had significant effects on the biomarkers of oxidative damage and antioxidant status, with rats fed the synthetic/fish oil diet having the lowest levels of oxidative damage and the highest antioxidant status. When boysenberry extract was added to the diet, there was little change in 8-oxo-2'-deoxyguanosine excretion in urine, oxidative damage to proteins decreased, and plasma malondialdehyde either increased or decreased depending on the basal diet. This study showed that boysenberry extract functioned as an in vivo antioxidant and raised the antioxidant status of plasma while decreasing some biomarkers of oxidative damage, but the effect was highly modified by basal diet. Our results are further evidence of complex interactions among dietary antioxidants, background nutritional status as determined by diet, and the biochemical nature of the compartments in which antioxidants function.

Testing the Effects of dl-Alpha-Tocopherol Supplementation on Oxidative Damage, Total Antioxidant Protection and the Sex-Specific Responses of Reproductive Effort and Lifespan to Dietary Manipulation in Australian Field Crickets (Teleogryllus commodus)

PubMed Central

Archer, C. Ruth; Hempenstall, Sarah; Royle, Nick J.; Selman, Colin; Willis, Sheridan; Rapkin, James; Blount, Jon D.; Hunt, John

2015-01-01

The oxidative stress theory predicts that the accumulation of oxidative damage causes aging. More generally, oxidative damage could be a cost of reproduction that reduces survival. Both of these hypotheses have mixed empirical support. To better understand the life-history consequences of oxidative damage, we fed male and female Australian field crickets (Teleogryllus commodus) four diets differing in their protein and carbohydrate content, which have sex-specific effects on reproductive effort and lifespan. We supplemented half of these crickets with the vitamin E isoform dl-alpha-tocopherol and measured the effects of nutrient intake on lifespan, reproduction, oxidative damage and antioxidant protection. We found a clear trade-off between reproductive effort and lifespan in females but not in males. In direct contrast to the oxidative stress theory, crickets fed diets that improved their lifespan had high levels of oxidative damage to proteins. Supplementation with dl-alpha-tocopherol did not significantly improve lifespan or reproductive effort. However, males fed diets that increased their reproductive investment experienced high oxidative damage to proteins. While this suggests that male reproductive effort could elevate oxidative damage, this was not associated with reduced male survival. Overall, these results provide little evidence that oxidative damage plays a central role in mediating life-history trade-offs in T. commodus. PMID:26783958

Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells.

PubMed

Zhai, Qingfeng; Duan, Huawei; Wang, Yadong; Huang, Chuanfeng; Niu, Yong; Dai, Yufei; Bin, Ping; Liu, Qingjun; Chen, Wen; Ma, Junxiang; Zheng, Yuxin

2012-08-01

Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose-effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chronic Oxidative Damage together with Genome Repair Deficiency in the Neurons is a Double Whammy for Neurodegeneration: Is Damage Response Signaling a Potential Therapeutic Target?

PubMed Central

Wang, Haibo; Dharmalingam, Prakash; Vasquez, Velmarini; Mitra, Joy; Boldogh, Istvan; Rao, K. S.; Kent, Thomas A.; Mitra, Sankar; Hegde, Muralidhar L.

2016-01-01

A foremost challenge for the neurons, which are among the most oxygenated cells, is the genome damage caused by chronic exposure to endogenous reactive oxygen species (ROS), formed as cellular respiratory byproducts. Strong metabolic activity associated with high transcriptional levels in these long lived post-mitotic cells render them vulnerable to oxidative genome damage, including DNA strand breaks and mutagenic base lesions. There is growing evidence for the accumulation of unrepaired DNA lesions in the central nervous system (CNS) during accelerated ageing and progressive neurodegeneration. Several germ line mutations in DNA repair or DNA damage response (DDR) signaling genes are uniquely manifested in the phenotype of neuronal dysfunction and are etiologically linked to many neurodegenerative disorders. Studies in our lab and elsewhere revealed that pro-oxidant metals, ROS and misfolded amyloidogenic proteins not only contribute to genome damage in CNS, but also impede their repair/DDR signaling leading to persistent damage accumulation, a common feature in sporadic neurodegeneration. Here, we have reviewed recent advances in our understanding of the etiological implications of DNA damage vs. repair imbalance, abnormal DDR signaling in triggering neurodegeneration and potential of DDR as a target for the amelioration of neurodegenerative diseases. PMID:27663141

The effect of predator exposure and reproduction on oxidative stress parameters in the Catarina scallop Argopecten ventricosus.

PubMed

Guerra, C; Zenteno-Savín, T; Maeda-Martínez, A N; Abele, D; Philipp, E E R

2013-05-01

Predation is known to impact growth and reproduction, and the physiological state of the prey, including its susceptibility to oxidative stress. In this study, we investigated how prolonged exposure to predators modulates tissue specific antioxidant defense and oxidative damage in the short-lived epibenthic scallop Argopecten ventricosus (2years maximum lifespan). Scallops that were experimentally exposed to predators had not only lower antioxidant capacities (superoxide dismutase and catalase), but also lower oxidative damage (protein carbonyls and TBARS=thiobarbituric acid reactive substances including lipid peroxides) in gills and mantle compared to individuals not exposed to predators. In contrast, oxidative damage in the swimming muscle was higher in predator-exposed scallops. When predator-exposed scallops were on the verge of spawning, levels of oxidative damage increased in gills and mantle in spite of a parallel increase in antioxidant defense in both tissues. Levels of oxidative damage increased also in the swimming muscle whereas muscle antioxidant capacities decreased. Interestingly, post-spawned scallops restored antioxidant capacities and oxidative damage to immature levels, suggesting they can recover from spawning-related oxidative stress. Our results show that predator exposure and gametogenesis modulate oxidative damage in a tissue specific manner and that high antioxidant capacities do not necessarily coincide with low oxidative damage. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2013-01-01

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

Effect of Creep and Oxidation on Reduced Creep-Fatigue life of Ni-based Alloy 617 at 850 C

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

Chen, Xiang; Yang, Zhiqing; Sokolov, Mikhail A

Low cycle fatigue (LCF) and creep fatigue testing of Ni-based alloy 617 was carried out at 850 C. Compared with its LCF life, the material s creep fatigue life decreases to different extents depending on test conditions. To elucidate the microstructure-fatigue property relationship for alloy 617 and the effect of creep and oxidation on its fatigue life, systematic microstructural investigations were carried out using scanning electron microscopy, energy-dispersive X-ray spectroscopy, and electron backscatter diffraction (EBSD). In LCF tests, as the total strain range increased, deformations concentrated near high angle grain boundaries (HAGBs). The strain hold period in the creep fatiguemore » tests introduced additional creep damage to the material, which revealed the detrimental effect of the strain hold time on the material fatigue life in two ways. First, the strain hold time enhanced the localized deformation near HAGBs, resulting in the promotion of intergranular cracking of alloy 617. Second, the strain hold time encouraged grain boundary sliding, which resulted in interior intergranular cracking of the material. Oxidation accelerated the initiation of intergranular cracking in alloy 617. In the crack propagation stage, if oxidation was promoted and the cyclic oxidation damage was greater than the fatigue damage, oxidation-assisted intergranular crack growth resulted in a significant reduction in the material s fatigue life.« less

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

2002-01-01

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

DNA damage in cells exhibiting radiation-induced genomic instability

DOE PAGES

Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

2015-02-22

Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

Alkaline Comet Assay for Assessing DNA Damage in Individual Cells.

PubMed

Pu, Xinzhu; Wang, Zemin; Klaunig, James E

2015-08-06

Single-cell gel electrophoresis, commonly called a comet assay, is a simple and sensitive method for assessing DNA damage at the single-cell level. It is an important technique in genetic toxicological studies. The comet assay performed under alkaline conditions (pH >13) is considered the optimal version for identifying agents with genotoxic activity. The alkaline comet assay is capable of detecting DNA double-strand breaks, single-strand breaks, alkali-labile sites, DNA-DNA/DNA-protein cross-linking, and incomplete excision repair sites. The inclusion of digestion of lesion-specific DNA repair enzymes in the procedure allows the detection of various DNA base alterations, such as oxidative base damage. This unit describes alkaline comet assay procedures for assessing DNA strand breaks and oxidative base alterations. These methods can be applied in a variety of cells from in vitro and in vivo experiments, as well as human studies. Copyright © 2015 John Wiley & Sons, Inc.

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

PubMed

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

2001-12-19

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

Effects of Weather Conditions on Oxidative Stress, Oxidative Damage, and Antioxidant Capacity in a Wild-Living Mammal, the European Badger (Meles meles).

PubMed

Bilham, Kirstin; Newman, Chris; Buesching, Christina D; Noonan, Michael J; Boyd, Amy; Smith, Adrian L; Macdonald, David W

Wild-living animals are subject to weather variability that may cause the generation of reactive oxygen species, resulting in oxidative stress and tissue damage, potentially driving demographic responses. Our 3-yr field study investigated the effects of seasonal weather conditions on biomarkers for oxidative stress, oxidative damage, and antioxidant defense in the European badger (Meles meles). We found age class effects: cubs were more susceptible to oxidative stress and oxidative damage than adults, especially very young cubs in the spring, when they also exhibited lower antioxidant biomarkers than adults. Although previous studies have found that intermediate spring and summer rainfall and warmer temperatures favor cub survival, counterintuitively these conditions were associated with more severe oxidative damage. Oxidative damage was high in cubs even when antioxidant biomarkers were high. In contrast, adult responses accorded with previous survival analyses. Wetter spring and summer conditions were associated with higher oxidative damage, but they were also associated with higher antioxidant biomarkers. Autumnal weather did not vary substantially from normative values, and thus effects were muted. Winter carryover effects were partially evident, with drier and milder conditions associated with greater oxidative damage in the following spring but also with higher antioxidant capacity. Plausibly, warmer conditions promoted more badger activity, with associated metabolic costs at a time of year when food supply is limited. Modeling biomarkers against projected climate change scenarios predicted greater future risks of oxidative damage, although not necessarily exceeding antioxidant capacity. This interdisciplinary approach demonstrates that individual adaptive physiological responses are associated with variation in natural environmental conditions.

Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: evidence for oxidatively DNA damage generation.

PubMed

Pinto, A Viviana; Deodato, Elder L; Cardoso, Janine S; Oliveira, Eliza F; Machado, Sérgio L; Toma, Helena K; Leitão, Alvaro C; de Pádula, Marcelo

2010-06-01

Although titanium dioxide (TiO(2)) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO(2) is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO(2)-UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO(2) associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO(2) plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO(2) protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO(2) plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO(2) plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine. Copyright 2010 Elsevier B.V. All rights reserved.

Differential effects of vitamins E and C and carotenoids on growth, resistance to oxidative stress, fledging success and plumage colouration in wild great tits.

PubMed

Marri, Viviana; Richner, Heinz

2014-05-01

Oxidative stress is the imbalance between the production of reactive species and antioxidants, which causes damage to lipids, proteins and DNA. Antioxidants, like vitamins and carotenoids, can limit oxidative damage and can therefore regulate the trade-off between growth, which is a period of high reactive species production, and self-maintenance. However, the role of carotenoids as antioxidants in vivo has been debated, and it has been suggested that carotenoid-based signals indicate the availability of non-pigmentary antioxidants (e.g. vitamins) that protect carotenoids from oxidation, known as the 'protection hypothesis'. To evaluate the importance of vitamins versus carotenoids as antioxidants during growth and to test the protection hypothesis, we supplemented nestling great tits, Parus major, 3, 5 and 7 days after hatching with a single dose of carotenoids and/or vitamins in a 2×2 full-factorial design. We subsequently measured body condition, antioxidant capacity, oxidative damage, fledging success and plumage reflectance. Vitamins enhanced antioxidant capacity, but did not affect oxidative damage. Vitamin-treated nestlings had higher growth rates and higher probability of fledging. In contrast, carotenoids did not affect any of these traits. Furthermore, carotenoid-based colouration increased over the breeding season in nestlings that received vitamins only. This study shows that vitamins are limiting for growth rate and fledging success, and suggests that vitamins could regulate the trade-off between growth and self-maintenance in favour of the former. Moreover, our results are consistent with the idea that carotenoids are minor antioxidants in birds, but they do not support the protection hypothesis.

Low-concentration exposure to BPA, BPF and BPAF induces oxidative DNA bases lesions in human peripheral blood mononuclear cells.

PubMed

Mokra, Katarzyna; Woźniak, Katarzyna; Bukowska, Bożena; Sicińska, Paulina; Michałowicz, Jaromir

2018-06-01

Because bisphenol A (BPA) and some of its analogs have been supposed to influence development of cancer, we have assessed the effect of BPA, bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) on DNA bases oxidation, which is a key process in cancer initiation. The analysis was conducted on human peripheral blood mononuclear cells (PBMCs), which are very useful model to assess genotoxic potential of various toxicants in different cell types. In order to determine oxidative damage to DNA pyrimidines and purines, alkaline version of the comet assay with DNA glycosylases, i.e. endonuclease III (Nth) and human 8-oxoguanine DNA glycosylase (hOGG1) was used. PBMCs were exposed to BPA or its analogs in the concentrations of 0.01, 0.1 and 1 μg/mL for 4 h and 0.001, 0.01 and 0.1 μg/mL for 48 h. We have observed that BPA, BPS, BPF and particularly BPAF caused oxidative damage to DNA pyrimidines and more strongly to purines in human PBMCs. The results have also shown that BPS, which is the most commonly used as a substitute for BPA in the manufacture induced definitely the smallest oxidative DNA bases lesions in PBMCs. Moreover, we have noticed that BPA, BPF and BPAF caused DNA damage at very low concentration of 1 ng/mL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Poly-l-cysteine/electrospun copper oxide nanofibers-zinc oxide nanoparticles nanocomposite as sensing element of an electrochemical sensor for simultaneous determination of adenine and guanine in biological samples and evaluation of damage to dsDNA and DNA purine bases by UV radiation.

PubMed

Arvand, Majid; Sayyar Ardaki, Masoomeh

2017-09-15

A new nanocomposite film constructed of poly-l-cysteine/zinc oxide nanoparticles-electrospun copper oxide nanofibers (PLC/ZnO-NPs-CuO-NFs) was prepared on the surface of the graphite electrode (GE). The novel electrode was successfully applied for the simultaneous determination of guanine (G) and adenine (A), two of the most important components of DNA and RNA. The PLC/ZnO-NPs-CuO-NFs/GE enhanced the anodic peak currents of the purine bases conspicuously and could determine them sensitively and separately in 0.1 M phosphate buffer solution at the physiological pH (7.0). The synthesized nanofibers, nanoparticles and nanocomposite were characterized by different methods such as Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and energy dispersive X-ray analysis (EDS). Under the optimum operating conditions, linear calibration curves were obtained in the range of 0.05-6.78 and 0.01-3.87 μM with a detection limit of 12.48 and 1.25 nM for G and A, respectively. The proposed method was applied to quantify A and G in three different DNA samples with satisfactory results. In addition, damage to human blood double-stranded DNA (dsDNA) and DNA purine bases (liberated in previously hydrolyzed human blood dsDNA) caused by UV-C and UV-B were evaluated. The results demonstrated that the proposed biosensing platform not only provides a novel and sensitive approach to detecting DNA damage, but also can be used for simultaneous determination of purine bases and major products of DNA oxidative damage. Copyright © 2017 Elsevier B.V. All rights reserved.

Origins and consequences of DNA damage in male germ cells.

PubMed

Aitken, R John; De Iuliis, Geoffry N

2007-06-01

DNA damage in the male germline is associated with poor fertilization rates following IVF, defective preimplantation embryonic development, and high rates of miscarriage and morbidity in the offspring, including childhood cancer. This damage is poorly characterized, but is known to involve hypomethylation of key genes, oxidative base damage, endonuclease-mediated cleavage and the formation of adducts with xenobiotics and the products of lipid peroxidation. There are many possible causes of such DNA damage, including abortive apoptosis, the oxidative stress associated with male genital tract infection, exposure to redox cycling chemicals, and defects of spermiogenesis associated with the retention of excess residual cytoplasm. Physical factors such as exposure to radiofrequency electromagnetic radiation or mild scrotal heating can also induce DNA damage in mammalian spermatozoa, although the underlying mechanisms are unclear. Ultimately, resolving the precise nature of the DNA lesions present in the spermatozoa of infertile men will be an important step towards uncovering the aetiology of this damage and developing strategies for its clinical management.

Effect of T3 on metabolic response and oxidative stress in skeletal muscle from sedentary and trained rats.

PubMed

Venditti, Paola; Bari, Angela; Di Stefano, Lisa; Di Meo, Sergio

2009-02-01

We investigated whether swim training modifies the effect of T3-induced hyperthyroidism on metabolism and oxidative damage in rat muscle. Respiratory capacities, oxidative damage, levels of antioxidants, and susceptibility to oxidative challenge of homogenates were determined. Mitochondrial respiratory capacities, H2O2 release rates, and oxidative damage were also evaluated. T3-treated rats exhibited increases in muscle respiratory capacity, which were associated with enhancements in mitochondrial respiratory capacity and tissue mitochondrial protein content in sedentary and trained animals, respectively. Hormonal treatment induced muscle oxidative damage and GSH depletion. Both effects were reduced by training, which also attenuated tissue susceptibility to oxidative challenge. The changes in single antioxidant levels were slightly related to oxidative damage extent, but the examination of parameters affecting the susceptibility to oxidants indicated that training was associated with greater effectiveness of the muscle antioxidant system. Training also attenuated T3-induced increases in H2O2 production and, therefore, oxidative damage of mitochondria by lowering their content of autoxidizable electron carriers. The above results suggest that moderate training is able to reduce hyperthyroid state-linked tissue oxidative damage, increasing antioxidant protection and decreasing the ROS flow from the mitochondria to the cytoplasmic compartment.

UV irradiation-induced methionine oxidation in human skin keratins: Mass spectrometry-based non-invasive proteomic analysis.

PubMed

Lee, Seon Hwa; Matsushima, Keita; Miyamoto, Kohei; Oe, Tomoyuki

2016-02-05

Ultraviolet (UV) radiation is the major environmental factor that causes oxidative skin damage. Keratins are the main constituents of human skin and have been identified as oxidative target proteins. We have recently developed a mass spectrometry (MS)-based non-invasive proteomic methodology to screen oxidative modifications in human skin keratins. Using this methodology, UV effects on methionine (Met) oxidation in human skin keratins were investigated. The initial screening revealed that Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UVA (or UVB) irradiation of human tape-stripped skin. Subsequent liquid chromatography/electrospray ionization-MS and tandem MS analyses confirmed amino acid sequences and oxidation sites of tryptic peptides D(290)VDGAYMTK(298) (P1) and N(258)MQDMVEDYR(267) (P2). The relative oxidation levels of P1 and P2 increased in a time-dependent manner upon UVA irradiation. Butylated hydroxytoluene was the most effective antioxidant for artifactual oxidation of Met residues. The relative oxidation levels of P1 and P2 after UVA irradiation for 48 h corresponded to treatment with 100mM hydrogen peroxide for 15 min. In addition, Met(259) was oxidized by only UVA irradiation. The Met sites identified in conjunction with the current proteomic methodology can be used to evaluate skin damage under various conditions of oxidative stress. We demonstrated that the relative Met oxidation levels in keratins directly reflected UV-induced damages to human tape-stripped skin. Human skin proteins isolated by tape stripping were analyzed by MS-based non-invasive proteomic methodology. Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UV irradiation. Met(259) was oxidized by only UVA irradiation. Quantitative LC/ESI-SRM/MS analyses confirmed a time-dependent increase in the relative oxidation of target peptides (P1 and P2) containing these Met residues, upon UVA irradiation of isolated human skin. The relative oxidation levels of P1 and P2 along with the current proteomic methodology could be applied to the assessment of oxidative stress levels in skin after exposure to sunlight. Copyright © 2015 Elsevier B.V. All rights reserved.

New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.

PubMed

Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L

2015-05-01

Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory proteins guiding distinct BER sub-pathways.

Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

PubMed

Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

2016-11-01

In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

The Redox Stress Hypothesis of Aging

PubMed Central

Sohal, Rajindar S.; Orr, William C.

2011-01-01

The main objective of this review is to examine the role of the endogenous reactive oxygen/nitrogen species (ROS) in the aging process. Until relatively recently, ROS were considered to be potentially toxic by-products of aerobic metabolism, which, if not eliminated, may inflict structural damage on various macromolecules. Accrual of such damage over time was postulated to be responsible for the physiological deterioration in the post-reproductive phase of life and eventually the death of the organism. This “structural damage-based oxidative stress” hypothesis has received support from the age-associated increases in the rates of ROS production and the steady-state amounts of oxidized macromolecules; however, there are increasing indications that structural damage alone is insufficient to satisfactorily explain the age-associated functional losses. The level of oxidative damage, accrued during aging, often does not match the magnitude of functional losses. Although experimental augmentations of antioxidant defenses tend to enhance resistance to induced oxidative stress, such manipulations are generally ineffective in the extension of life span of long-lived strains of animals. More recently, in a major conceptual shift, ROS have been found to be physiologically vital for signal transduction, gene regulation and redox regulation, among others, implying that their complete elimination would be harmful. An alternative notion, advocated here, termed “redox stress hypothesis”, proposes that aging-associated functional losses are primarily caused by a progressive pro-oxidizing shift in the redox state of the cells, which leads to the over-oxidation of redox-sensitive protein thiols and the consequent disruption of the redox-regulated signaling mechanisms. PMID:22080087

Oxidative DNA damage during sleep periods among nightshift workers.

PubMed

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

2016-08-01

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

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

PubMed Central

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

2008-01-01

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

The Effect of Fatty Acids to Protect Forward Osmosis Membranes from Damage

NASA Technical Reports Server (NTRS)

Romero Mangado, Jaione; Parodi, Jurek; Stefanson, Ofir; Lathrop, Cooper; Lewis, Madeleine; Ferrara, Alessandro; Tatum, Simone; Flynn, Michael

2017-01-01

NASA has conducted research and development on forward osmosis (FO) membranes for wastewater reclamation in space since 1993. The lessons learned during operation of the International Space Station and FO based technologies on the ground taught us that reliability is a key limitation. Membranes are susceptible to organic fouling, oxidation and calcium scaling, and these factors tend to damage the membrane reducing their operating life and performance. The development of a Synthetic Biological Membrane (SBM), a membrane that mimics naturally occurring biological processes, will mitigate membrane damage and improve reliability. The SBM is a lipid-based membrane with a protective fatty acid layer configured for use in a FO water purification system. In this configuration, the protective layer on the surface of the lipid membrane is composed of fatty acids (FA). The FA interact with the chemicals found in the wastewater feed, and protect the membrane from damage. In this study, we conducted preliminary experiments to determine the feasibility of using fatty acids to alleviate damage from calcium scaling, oxidation and organic fouling.

Aluminum Pitting Corrosion in Halide Media: A Quantum Model and Empirical Evidence

NASA Astrophysics Data System (ADS)

Lashgari, Mohsen; Kianpour, Effat; Mohammadi, Esmaeil

2013-12-01

The phenomenon of localized damage of aluminum oxide surface in the presence of halide anions was scrutinized at an atomistic level, through the cluster approach and density functional theory. The phenomenon was also investigated empirically through Tafel polarization plots and scanning electron microscopy. A distinct behavior witnessed in the fluoride medium was justified through the hard-soft acid-base principle. The atomistic investigations revealed the greatest potency for chloride entrance into the metal oxide lattice and rationalized to the severity of damage. The interaction of halide anions with the oxide surface causing some displacements on the position of Al atoms provides a mechanistic insight of the phenomenon.

Synergistic Effects of Temperature, Oxidation and Stress Level on Fatigue Damage Evolution and Lifetime Prediction of Cross-Ply SiC/CAS Ceramic-Matrix Composites Through Hysteresis-Based Parameters

NASA Astrophysics Data System (ADS)

Li, Longbiao

2017-12-01

The damage development and cyclic fatigue lifetime of cross-ply SiC/CAS ceramic-matrix composites have been investigated at different testing temperatures in air atmosphere. The relationships between the fatigue hysteresis-based damage parameters, i.e., fatigue hysteresis dissipated energy, fatigue hysteresis modulus and fatigue peak strain and the damage mechanisms of matrix multicracking, fiber/matrix interface debonding, interface sliding and fibers failure, have been established. With the increase in the cycle number, the evolution of the fatigue hysteresis modulus, fatigue peak strain and fatigue hysteresis dissipated energy depends upon the fatigue peak stress levels, interface and fibers oxidation and testing temperature. The fatigue life S-N curves of cross-ply SiC/CAS composite at room and elevated temperatures have been predicted, and the fatigue limit stresses at room temperature, 750 and 850 °C, are 50, 36 and 30% of the tensile strength, respectively.

Dissimilar effect of perming and bleaching treatments on cuticles: advanced hair damage model based on elution and oxidation of S100A3 protein.

PubMed

Kizawa, Kenji; Inoue, Takafumi; Yamaguchi, Masahito; Kleinert, Peter; Troxler, Heinz; Heizmann, Claus W; Iwamoto, Yoshimichi

2005-01-01

Hair treatment chemicals induce sudden and severe hair damage. In this study, we examined cuticles from untreated, permed, and bleached hair that were mechanically discriminated by shaking in water. Both perming and bleaching treatments are prone to easily delaminate cuticles. Confocal microscopy revealed that the cuticles of permed hair were delaminated with larger pieces than untreated ones. On the other hand, the cuticles of bleached hair tend to fragment into small peptides. At the minimum concentration of thioglycolate required to elute S100A3 protein from the endocuticle into the reductive permanent waving lotion, enlarged delaminated cuticle fragments were observed. Although S100A3 is retained in bleached hair, S100A3 is irreversibly oxidized upon bleaching treatment. It is likely that the oxidative cleavage of disulfide bonds between cuticle-constituting proteins, including S100A3, results in the fragile property of cuticles. Here we present a more comprehensive model of hair damage based on a diverse mechanism of cuticle delamination.

Viewing oxidative stress through the lens of oxidative signalling rather than damage

PubMed Central

Ruban, Alexander V.; Noctor, Graham

2017-01-01

Concepts of the roles of reactive oxygen species (ROS) in plants and animals have shifted in recent years from focusing on oxidative damage effects to the current view of ROS as universal signalling metabolites. Rather than having two opposing activities, i.e. damage and signalling, the emerging concept is that all types of oxidative modification/damage are involved in signalling, not least in the induction of repair processes. Examining the multifaceted roles of ROS as crucial cellular signals, we highlight as an example the loss of photosystem II function called photoinhibition, where photoprotection has classically been conflated with oxidative damage. PMID:28270560

Destructive behavior of iron oxide in projectile impact

NASA Astrophysics Data System (ADS)

Shang, Wang; Xiaochen, Wang; Quan, Yang; Zhongde, Shan

2017-12-01

The damage strain values of Q235-A surface oxide scale were obtained by scanning electron microscopy (SEM/EDS) and universal tensile testing machine. The finite element simulation was carried out to study the destruction effects of oxidation at different impact rates. The results show that the damage value of the oxide strain is 0.08%. With the increase of the projectile velocity, the damage area of the oxide scale is increased, and the damage area is composed of the direct destruction area and the indirect failure area. The indirect damage area is caused by the stress/strain to the surrounding expansion after the impact of the steel body.

Profiling cytosine oxidation in DNA by LC-MS/MS.

PubMed

Samson-Thibault, Francois; Madugundu, Guru S; Gao, Shanshan; Cadet, Jean; Wagner, J Richard

2012-09-17

Spontaneous and oxidant-induced damage to cytosine is probably the main cause of CG to TA transition mutations in mammalian genomes. The reaction of hydroxyl radical (·OH) and one-electron oxidants with cytosine derivatives produces numerous oxidation products, which have been identified in large part by model studies with monomers and short oligonucleotides. Here, we developed an analytical method based on LC-MS/MS to detect 10 oxidized bases in DNA, including 5 oxidation products of cytosine. The utility of this method is demonstrated by the measurement of base damage in isolated calf thymus DNA exposed to ionizing radiation in aerated aqueous solutions (0-200 Gy) and to well-known Fenton-like reactions (Fe(2+) or Cu(+) with H(2)O(2) and ascorbate). The following cytosine modifications were quantified as modified 2'-deoxyribonucleosides upon exposure of DNA to ionizing radiation in aqueous aerated solution: 5-hydroxyhydantoin (Hyd-Ura) > 5-hydroxyuracil (5-OHUra) > 5-hydroxycytosine (5-OHCyt) > 5,6-dihydroxy-5,6-dihydrouracil (Ura-Gly) > 1-carbamoyl-4,5-dihydroxy-2-oxoimidazolidine (Imid-Cyt). The total yield of cytosine oxidation products was comparable to that of thymine oxidation products (5,6-dihydroxy-5,6-dihydrothymine (Thy-Gly), 5-hydroxy-5-methylhydantotin (Hyd-Thy), 5-(hydroxymethyl)uracil (5-HmUra), and 5-formyluracil (5-ForUra)) as well as the yield of 8-oxo-7,8-dihydroguanine (8-oxoGua). The major oxidation product of cytosine in DNA was Hyd-Ura. In contrast, the formation of Imid-Cyt was a minor pathway of DNA damage, although it is the major product arising from irradiation of the monomers, cytosine, and 2'-deoxycytidine. The reaction of Fenton-like reagents with DNA gave a different distribution of cytosine derived products compared to ionizing radiation, which likely reflects the reaction of metal ions with intermediate peroxyl radicals or hydroperoxides. The analysis of the main cytosine oxidation products will help elucidate the complex mechanism of oxidative degradation of cytosine in DNA and probe the consequences of these reactions in biology and medicine.

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

Waldhoff, Stephanie T.; Anthoff, David; Rose, Steven K.

We use FUND 3.8 to estimate the social cost of four greenhouse gases: carbon dioxide, methane, nitrous oxide, and sulphur hexafluoride emissions. The damage potential for each gas—the ratio of the social cost of the non-carbon dioxide greenhouse gas to the social cost of carbon dioxide—is also estimated. The damage potentials are compared to several metrics, focusing in particular on the global warming potentials, which are frequently used to measure the trade-off between gases in the form of carbon dioxide equivalents. We find that damage potentials could be significantly higher than global warming potentials. This finding implies that previous papersmore » have underestimated the relative importance of reducing non-carbon dioxide greenhouse gas emissions from an economic damage perspective. We show results for a range of sensitivity analyses: carbon dioxide fertilization on agriculture productivity, terrestrial feedbacks, climate sensitivity, discounting, equity weighting, and socioeconomic and emissions scenarios. The sensitivity of the results to carbon dioxide fertilization is a primary focus as it is an important element of climate change that has not been considered in much of the previous literature. We estimate that carbon dioxide fertilization has a large positive impact that reduces the social cost of carbon dioxide with a much smaller effect on the other greenhouse gases. As a result, our estimates of the damage potentials of methane and nitrous oxide are much higher compared to estimates that ignore carbon dioxide fertilization. As a result, our base estimates of the damage potential for methane and nitrous oxide that include carbon dioxide fertilization are twice their respective global warming potentials. Our base estimate of the damage potential of sulphur hexafluoride is similar to the one previous estimate, both almost three times the global warming potential.« less

Evaluation of Toxic Effects of Aeration and Trichloroethylene Oxidation on Methanotrophic Bacteria Grown with Different Nitrogen Sources

PubMed Central

Chu, Kung-Hui; Alvarez-Cohen, Lisa

1999-01-01

In this study we evaluated specific and nonspecific toxic effects of aeration and trichloroethylene (TCE) oxidation on methanotrophic bacteria grown with different nitrogen sources (nitrate, ammonia, and molecular nitrogen). The specific toxic effects, exerted directly on soluble methane monooxygenase (sMMO), were evaluated by comparing changes in methane uptake rates and naphthalene oxidation rates following aeration and/or TCE oxidation. Nonspecific toxic effects, defined as general cellular damage, were examined by using a combination of epifluorescent cellular stains to measure viable cell numbers based on respiratory activity and measuring formate oxidation activities following aeration and TCE transformation. Our results suggest that aeration damages predominantly sMMO rather than other general cellular components, whereas TCE oxidation exerts a broad range of toxic effects that damage both specific and nonspecific cellular functions. TCE oxidation caused sMMO-catalyzed activity and respiratory activity to decrease linearly with the amount of substrate degraded. Severe TCE oxidation toxicity resulted in total cessation of the methane, naphthalene, and formate oxidation activities and a 95% decrease in the respiratory activity of methanotrophs. The failure of cells to recover even after 7 days of incubation with methane suggests that cellular recovery following severe TCE product toxicity is not always possible. Our evidence suggests that generation of greater amounts of sMMO per cell due to nitrogen fixation may be responsible for enhanced TCE oxidation activities of nitrogen-fixing methanotrophs rather than enzymatic protection mechanisms associated with the nitrogenase enzymes. PMID:9925614

Measurement of oxidative DNA damage by gas chromatography-mass spectrometry: ethanethiol prevents artifactual generation of oxidized DNA bases.

PubMed Central

Jenner, A; England, T G; Aruoma, O I; Halliwell, B

1998-01-01

Analysis of oxidative damage to DNA bases by GC-MS enables identification of a range of base oxidation products, but requires a derivatization procedure. However, derivatization at high temperature in the presence of air can cause 'artifactual' oxidation of some undamaged bases, leading to an overestimation of their oxidation products, including 8-hydroxyguanine. Therefore derivatization conditions that could minimize this problem were investigated. Decreasing derivatization temperature to 23 degrees C lowered levels of 8-hydroxyguanine, 8-hydroxyadenine, 5-hydroxycytosine and 5-(hydroxymethyl)uracil measured by GC-MS in hydrolysed calf thymus DNA. Addition of the reducing agent ethanethiol (5%, v/v) to DNA samples during trimethylsilylation at 90 degrees C also decreased levels of these four oxidized DNA bases as well as 5-hydroxyuracil. Removal of guanine from hydrolysed DNA samples by treatment with guanase, prior to derivatization, resulted in 8-hydroxyguanine levels (54-59 pmol/mg of DNA) that were significantly lower than samples not pretreated with guanase, independent of the derivatization conditions used. Only hydrolysed DNA samples that were derivatized at 23 degrees C in the presence of ethanethiol produced 8-hydroxyguanine levels (56+/-8 pmol/mg of DNA) that were as low as those of guanase-pretreated samples. Levels of other oxidized bases were similar to samples derivatized at 23 degrees C without ethanethiol, except for 5-hydroxycytosine and 5-hydroxyuracil, which were further decreased by ethanethiol. Levels of 8-hydroxyguanine, 8-hydroxyadenine and 5-hydroxycytosine measured in hydrolysed calf thymus DNA by the improved procedures described here were comparable with those reported previously by HPLC with electrochemical detection and by GC-MS with prepurification to remove undamaged base. We conclude that artifactual oxidation of DNA bases during derivatization can be prevented by decreasing the temperature to 23 degrees C, removing air from the derivatization reaction and adding ethanethiol. PMID:9531471

Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells

PubMed Central

Yang, Di; Fletcher, Sally C.; Vendrell, Iolanda; Fischer, Roman; Legrand, Arnaud J.

2017-01-01

Abstract Ataxia telangiectasia (A-T) is a syndrome associated with loss of ATM protein function. Neurodegeneration and cancer predisposition, both hallmarks of A-T, are likely to emerge as a consequence of the persistent oxidative stress and DNA damage observed in this disease. Surprisingly however, despite these severe features, a lack of functional ATM is still compatible with early life, suggesting that adaptation mechanisms contributing to cell survival must be in place. Here we address this gap in our knowledge by analysing the process of human fibroblast adaptation to the lack of ATM. We identify profound rearrangement in cellular proteostasis occurring very early on after loss of ATM in order to counter protein damage originating from oxidative stress. Change in proteostasis, however, is not without repercussions. Modulating protein turnover in ATM-depleted cells also has an adverse effect on the DNA base excision repair pathway, the major DNA repair system that deals with oxidative DNA damage. As a consequence, the burden of unrepaired endogenous DNA lesions intensifies, progressively leading to genomic instability. Our study provides a glimpse at the cellular consequences of loss of ATM and highlights a previously overlooked role for proteostasis in maintaining cell survival in the absence of ATM function. PMID:28973444

DNA Oxidation Profiles of Copper Phenanthrene Chemical Nucleases

NASA Astrophysics Data System (ADS)

Molphy, Zara; Slator, Creina; Chatgilialoglu, Chryssostomos; Kellett, Andrew

2015-04-01

The deleterious effects of metal-catalyzed reactive oxygen species (ROS) in biological systems can be seen in a wide variety of pathological conditions including cancer, cardiovascular disease, ageing, and neurodegenerative disorder. On the other hand however, targeted ROS production in the vicinity of nucleic acids - as demonstrated by metal-activated bleomycin - has paved the way for ROS-active chemotherapeutic drug development. Herein we report mechanistic investigations into the oxidative nuclease activity and redox properties of copper(II) developmental therapeutics [Cu(DPQ)(phen)]2+ (Cu-DPQ-Phen), [Cu(DPPZ)(phen)]2+ (Cu-DPPZ-Phen), and [{Cu(phen)2}2(μ-terph)](terph) (Cu-Terph), with results being compared directly to Sigman’s reagent [Cu(phen)2]2+ throughout (phen = 1,10-phenanthroline; DPQ = dipyridoquinoxaline; DPPZ = dipyridophenazine). Oxidative DNA damage was identified at the minor groove through use of surface bound recognition elements of methyl green, netropsin, and [Co(NH3)6]Cl3 that functioned to control complex accessibility at selected regions. ROS-specific scavengers and stabilisers were employed to identify the cleavage process, the results of which infer hydrogen peroxide produced metal-hydroxo or free hydroxyl radicals (•OH) as the predominant species. The extent of DNA damage owing to these radicals was then quantified through 8-oxo-2'-deoxyguanosine (8-oxo-dG) lesion detection under ELISA protocol with the overall trend following Cu-DPQ-Phen > Cu-Terph > Cu-Phen > Cu-DPPZ. Finally, the effects of oxidative damage on DNA replication processes were investigated using the polymerase chain reaction (PCR) where amplification of 120 base pair DNA sequences of varying base content were inhibited - particularly along A-T rich chains - through oxidative damage of the template strands.

Combustion products of 1,3-butadiene inhibit catalase activity and induce expression of oxidative DNA damage repair enzymes in human bronchial epithelial cells.

PubMed

Kennedy, Christopher H; Catallo, W James; Wilson, Vincent L; Mitchell, James B

2009-10-01

1,3-Butadiene, an important petrochemical, is commonly burned off when excess amounts need to be destroyed. This combustion process produces butadiene soot (BDS), which is composed of a complex mixture of polycyclic aromatic hydrocarbons in particulates ranging in size from <1 microm to 1 mm. An organic extract of BDS is both cytotoxic and genotoxic to normal human bronchial epithelial (NHBE) cells. Based on the oxidizing potential of BDS, we hypothesized that an organic extract of this particulate matter would (1) cause enzyme inactivation due to protein amino acid oxidation and (2) induce oxidative DNA damage in NHBE cells. Thus, our aims were to determine the effect of butadiene soot ethanol extract (BSEE) on both enzyme activity and the expression of proteins involved in the repair of oxidative DNA damage. Catalase was found to be sensitive to BDS as catalase activity was potently diminished in the presence of BSEE. Using Western analysis, both the alpha isoform of human 8-oxoguanine DNA glycosylase (alpha-hOGG1) and human apurinic/apyrimidinic endonuclease (APE-1) were shown to be significantly overexpressed as compared to untreated controls after exposure of NHBE cells to BSEE. Our results indicate that BSEE is capable of effectively inactivating the antioxidant enzyme catalase, presumably via oxidation of protein amino acids. The presence of oxidized biomolecules may partially explain the extranuclear fluorescence that is detected when NHBE cells are treated with an organic extract of BDS. Overexpression of both alpha-hOGG1 and APE-1 proteins following treatment of NHBE cells with BSEE suggests that this mixture causes oxidative DNA damage.

Combustion products of 1,3-butadiene inhibit catalase activity and induce expression of oxidative DNA damage repair enzymes in human bronchial epithelial cells

PubMed Central

Kennedy, Christopher H.; Catallo, W. James; Wilson, Vincent L.; Mitchell, James B.

2012-01-01

1,3-Butadiene, an important petrochemical, is commonly burned off when excess amounts need to be destroyed. This combustion process produces butadiene soot (BDS), which is composed of a complex mixture of polyaromatic hydrocarbons in particulates ranging in size from <1μm to 1 mm. An organic extract of BDS is both cytotoxic and genotoxic to normal human bronchial epithelial (NHBE) cells. Based on the oxidizing potential of BDS, we hypothesized that an organic extract of this particulate matter would: 1) cause enzyme inactivation due to protein amino acid oxidation; and 2) induce oxidative DNA damage in NHBE cells. Thus, our aims were to determine the effect of butadiene soot ethanol extract (BSEE) on both enzyme activity and expression of proteins involved in the repair of oxidative DNA damage. Catalase was found to be sensitive to BDS as catalase activity was potently diminished in the presence of BSEE. Using Western analysis, both the alpha isoform of human 8-oxoguanine DNA glycosylase (α-hOGG1) and human apurinic/apyrimidinic endonuclease (APE-1) were shown to be significantly overexpressed as compared to untreated controls after exposure of NHBE cells to BSEE. Our results indicate that BSEE is capable of effectively inactivating the antioxidant enzyme catalase, presumably via oxidation of protein amino acids. The presence of oxidized proteins may partially explain the extranuclear fluorescence that is detected when NHBE cells are treated with an organic extract of BDS. Overexpression of both α-hOGG1 and APE-1 proteins following treatment of NHBE cells with BSEE suggests that this mixture causes oxidative DNA damage. PMID:18685817

Oxidative profiles of LDL and HDL isolated from women with preeclampsia.

PubMed

León-Reyes, G; Maida-Claros, R F; Urrutia-Medina, A X; Jorge-Galarza, E; Guzmán-Grenfell, A M; Fuentes-García, S; Medina-Navarro, R; Moreno-Eutimio, M A; Muñoz-Sánchez, J L; Hicks, J J; Torres-Ramos, Y D

2017-05-16

Oxidative stress causes biochemical changes in lipids and proteins; these changes can induce damage to the vascular endothelium and create maternal complications that are characteristic of preeclampsia. In this study, we evaluated the oxidative profile of lipoproteins isolated from women with preeclampsia. Thirty women diagnosed with preeclampsia and thirty women without preeclampsia were included in the study. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, the formation of dityrosines, and the carbonylation of proteins were assessed as indicators of protein damage. The protective activity of HDL-c was evaluated by the paraoxonase-I activity present on the HDL-c particles. Serum lipid profiles were also quantified in both groups. Data were analysed using Student's t test and the Pearson correlation coefficient. Our results demonstrated in PE women evident oxidative changes in the lipids and proteins in HDL-c and LDL-c particles and the activity of the antioxidant enzyme PON-I decreased 59.9%. HDL-c exhibited self-defence, as demonstrated by the negative correlation between paraoxonase-I activity and the formation of lipohydroperoxides in HDL-c (r = -0.3755, p < 0.005). LDL-c and HDL-c isolated from women with preeclampsia show oxidative damage to lipids and proteins. We propose an oxidative profile based on the oxidation levels indicated by each of the markers used. We also found that paraoxonase-I is inactivated in the presence of lipohydroperoxides. Antioxidant support might be helpful to reduce oxidative stress in patients with preeclampsia. Further investigations are necessary to define the association between antioxidant activities and preeclampsia.

DNA damage, DNA susceptibility to oxidation and glutathione redox status in patients with Alzheimer's disease treated with and without memantine.

PubMed

Akkaya, Çağlayan; Yavuzer, Serap Sahin; Yavuzer, Hakan; Erkol, Gökhan; Bozluolcay, Melda; Dinçer, Yıldız

2017-07-15

The aim of the current study was to compare oxidative DNA damage, DNA susceptibility to oxidation, and ratio of GSH/GSSG in patients with Alzheimer's disease (AD) treated with acetylcholinesterase inhibitor (AChEI) and combined AChEI+memantine. The study included 67 patients with AD and 42 volunteers as control. DNA damage parameters (strand breaks, oxidized purines, H 2 O 2 -induced DNA damage) in lymphocyte DNA and GSH/GSSG ratio in erythrocytes were determined by the comet assay and spectrophotometric assay, respectively. DNA damage was found to be higher, GSH/GSSG ratio was found to be lower in the AD group than those in the control group. DNA strand breaks and H 2 O 2 -induced DNA damage were lower in the patients taking AChEI+memantine than those in the patients taking AChEI but no significant difference was determined between the groups for oxidized purines and GSH/GSSG ratio. In conclusion, increased systemic oxidative DNA damage and DNA susceptibility to oxidation may be resulted from diminished GSH/GSSG ratio in AD patients. Although DNA strand breaks and H 2 O 2 -induced DNA damage are lower in the AD patients treated with combined AChEI and memantine, this may not indicate protective effect of memantine against DNA oxidation due to similar levels of oxidized purines in the patients treated with AChEI and AChEI+memantine. Copyright © 2017 Elsevier B.V. All rights reserved.

Whey Peptide-Based Formulas With ω-3 Fatty Acids Are Protective in Lipopolysaccharide-Mediated Sepsis.

PubMed

Tsutsumi, Rie; Horikawa, Yousuke T; Kume, Katsuyoshi; Tanaka, Katsuya; Kasai, Asuka; Kadota, Takako; Tsutsumi, Yasuo M

2015-07-01

Sepsis and septic shock syndrome are among the leading causes of death in critically ill patients. Lipopolysaccharide (LPS) released by bacteria within the colon may translocate across a compromised epithelium, leading to oxidative stress, inflammation, sepsis, and eventually death. We examined the effects of a whey-based enteral formula high in cysteine (antioxidant precursor) and the addition of ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against a mouse model of LPS-induced sepsis. Mice were fed either a whey-based diet with EPA-DHA (PAF), a whey-based diet without EPA-DHA (PSTD), or a casein-based control diet (CONT). Mice fed PAF or PSTD were protected against LPS-induced weight loss. Whey-based diets suppressed inflammatory cytokine release and oxidative stress damage. Furthermore, PAF and PSTD were able to inhibit autophagy, a mechanism in which the cell recycles damaged organelles. These anti-inflammatory and antioxidative effects of PSTD and PAF resulted in decreased liver inflammation and intestinal damage and promoted protective microbiota within the intestines. These data suggest a clinical role for whey peptide-based diets in promoting healing and recovery in critically ill patients. © 2014 American Society for Parenteral and Enteral Nutrition.

Ntg1p, the base excision repair protein, generates mutagenic intermediates in yeast mitochondrial DNA.

PubMed

Phadnis, Naina; Mehta, Reema; Meednu, Nida; Sia, Elaine A

2006-07-13

Mitochondrial DNA is predicted to be highly prone to oxidative damage due to its proximity to free radicals generated by oxidative phosphorylation. Base excision repair (BER) is the primary repair pathway responsible for repairing oxidative damage in nuclear and mitochondrial genomes. In yeast mitochondria, three N-glycosylases have been identified so far, Ntg1p, Ogg1p and Ung1p. Ntg1p, a broad specificity N-glycosylase, takes part in catalyzing the first step of BER that involves the removal of the damaged base. In this study, we examined the role of Ntg1p in maintaining yeast mitochondrial genome integrity. Using genetic reporters and assays to assess mitochondrial mutations, we found that loss of Ntg1p suppresses mitochondrial point mutation rates, frameshifts and recombination rates. We also observed a suppression of respiration loss in the ntg1-Delta cells in response to ultraviolet light exposure implying an overlap between BER and UV-induced damage in the yeast mitochondrial compartment. Over-expression of the BER AP endonuclease, Apn1p, did not significantly affect the mitochondrial mutation rate in the presence of Ntg1p, whereas Apn1p over-expression in an ntg1-Delta background increased the frequency of mitochondrial mutations. In addition, loss of Apn1p also suppressed mitochondrial point mutations. Our work suggests that both Ntg1p and Apn1p generate mutagenic intermediates in the yeast mitochondrial genome.

Red light improves spermatozoa motility and does not induce oxidative DNA damage

NASA Astrophysics Data System (ADS)

Preece, Daryl; Chow, Kay W.; Gomez-Godinez, Veronica; Gustafson, Kyle; Esener, Selin; Ravida, Nicole; Durrant, Barbara; Berns, Michael W.

2017-04-01

The ability to successfully fertilize ova relies upon the swimming ability of spermatozoa. Both in humans and in animals, sperm motility has been used as a metric for the viability of semen samples. Recently, several studies have examined the efficacy of low dosage red light exposure for cellular repair and increasing sperm motility. Of prime importance to the practical application of this technique is the absence of DNA damage caused by radiation exposure. In this study, we examine the effect of 633 nm coherent, red laser light on sperm motility using a novel wavelet-based algorithm that allows for direct measurement of curvilinear velocity under red light illumination. This new algorithm gives results comparable to the standard computer-assisted sperm analysis (CASA) system. We then assess the safety of red light treatment of sperm by analyzing, (1) the levels of double-strand breaks in the DNA, and (2) oxidative damage in the sperm DNA. The results demonstrate that for the parameters used there are insignificant differences in oxidative DNA damage as a result of irradiation.

When theory and observation collide: Can non-ionizing radiation cause cancer?

PubMed

Havas, Magda

2017-02-01

This paper attempts to resolve the debate about whether non-ionizing radiation (NIR) can cause cancer-a debate that has been ongoing for decades. The rationale, put forward mostly by physicists and accepted by many health agencies, is that, "since NIR does not have enough energy to dislodge electrons, it is unable to cause cancer." This argument is based on a flawed assumption and uses the model of ionizing radiation (IR) to explain NIR, which is inappropriate. Evidence of free-radical damage has been repeatedly documented among humans, animals, plants and microorganisms for both extremely low frequency (ELF) electromagnetic fields (EMF) and for radio frequency (RF) radiation, neither of which is ionizing. While IR directly damages DNA, NIR interferes with the oxidative repair mechanisms resulting in oxidative stress, damage to cellular components including DNA, and damage to cellular processes leading to cancer. Furthermore, free-radical damage explains the increased cancer risks associated with mobile phone use, occupational exposure to NIR (ELF EMF and RFR), and residential exposure to power lines and RF transmitters including mobile phones, cell phone base stations, broadcast antennas, and radar installations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

PubMed

Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

2006-03-01

Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia.

PubMed

Aslan, Mehmet; Horoz, Mehmet; Kocyigit, Abdurrahim; Ozgonül, Saadet; Celik, Hakim; Celik, Metin; Erel, Ozcan

2006-10-10

Oxidant stress has been shown to play an important role in the pathogenesis of iron deficiency anemia. The aim of this study was to investigate the association between lymphocyte DNA damage, total antioxidant capacity and the degree of anemia in patients with iron deficiency anemia. Twenty-two female with iron deficiency anemia and 22 healthy females were enrolled in the study. Peripheral DNA damage was assessed using alkaline comet assay and plasma total antioxidant capacity was determined using an automated measurement method. Lymphocyte DNA damage of patients with iron deficiency anemia was significantly higher than controls (p<0.05), while total antioxidant capacity was significantly lower (p<0.001). While there was a positive correlation between total antioxidant capacity and hemoglobin levels (r=0.706, p<0.001), both total antioxidant capacity and hemoglobin levels were negatively correlated with DNA damage (r=-0.330, p<0.05 and r=-0.323, p<0.05, respectively). In conclusion, both oxidative stress and DNA damage are increased in IDA patients. Increased oxidative stress seems as an important factor that inducing DNA damage in those IDA patients. The relationships of oxidative stress and DNA damage with the severity of anemia suggest that both oxidative stress and DNA damage may, in part, have a role in the pathogenesis of IDA.

A Role for the Fifth G-Track in G-Quadruplex Forming Oncogene Promoter Sequences during Oxidative Stress: Do These "Spare Tires" Have an Evolved Function?

PubMed

Fleming, Aaron M; Zhou, Jia; Wallace, Susan S; Burrows, Cynthia J

2015-08-26

Uncontrolled inflammation or oxidative stress generates electron-deficient species that oxidize the genome increasing its instability in cancer. The G-quadruplex (G4) sequences regulating the c-MYC , KRAS , VEGF , BCL-2 , HIF-1α , and RET oncogenes, as examples, are targets for oxidation at loop and 5'-core guanines (G) as showcased in this study by CO 3 •- oxidation of the VEGF G4. Products observed include 8-oxo-7,8-dihydroguanine (OG), spiroiminodihydantoin (Sp), and 5-guanidinohydantoin (Gh). Our previous studies found that OG and Gh, when present in the four G-tracks of the solved structure for VEGF and c-MY C, were not substrates for the base excision repair (BER) DNA glycosylases in biologically relevant KCl solutions. We now hypothesize that a fifth G-track found a few nucleotides distant from the G4 tracks involved in folding can act as a "spare tire," facilitating extrusion of a damaged G-run into a large loop that then becomes a substrate for BER. Thermodynamic, spectroscopic, and DMS footprinting studies verified the fifth domain replacing a damaged G-track with OG or Gh at a loop or core position in the VEGF G4. These new "spare tire"-containing strands with Gh in loops are now found to be substrates for initiation of BER with the NEIL1, NEIL2, and NEIL3 DNA glycosylases. The results support a hypothesis in which regulatory G4s carry a "spare-tire" fifth G-track for aiding in the repair process when these sequences are damaged by radical oxygen species, a feature observed in a large number of these sequences. Furthermore, formation and repair of oxidized bases in promoter regions may constitute an additional example of epigenetic modification, in this case of guanine bases, to regulate gene expression in which the G4 sequences act as sensors of oxidative stress.

Mitochondrial Dysfunction in Retinal Diseases

PubMed Central

Barot, Megha; Gokulgandhi, Mitan R.; Mitra, Ashim K.

2015-01-01

The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases. PMID:21978133

Mitochondrial dysfunction in retinal diseases.

PubMed

Barot, Megha; Gokulgandhi, Mitan R; Mitra, Ashim K

2011-12-01

The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.

Synergistic Effects of Temperature, Oxidation and Multicracking Modes on Damage Evolution and Life Prediction of 2D Woven Ceramic-Matrix Composites under Tension-Tension Fatigue Loading

NASA Astrophysics Data System (ADS)

Longbiao, Li

2017-08-01

In this paper, the synergistic effects of temperature, oxidation and multicracking modes on damage evolution and life prediction in 2D woven ceramic-matrix composites (CMCs) have been investigated. The damage parameter of fatigue hysteresis dissipated energy and the interface shear stress were used to monitor the damage evolution inside of CMCs. Under cyclic fatigue loading, the fibers broken fraction was determined by combining the interface/fiber oxidation model, interface wear model and fibers statistical failure model at elevated temperature, based on the assumption that the fiber strength is subjected to two-parameter Weibull distribution and the load carried by broken and intact fibers satisfy the Global Load Sharing (GLS) criterion. When the broken fibers fraction approaches to the critical value, the composite fatigue fractures. The evolution of fatigue hysteresis dissipated energy, the interface shear stress and broken fibers fraction versus cycle number, and the fatigue life S-N curves of SiC/SiC at 1000, 1200 and 1300 °C in air and steam condition have been predicted. The synergistic effects of temperature, oxidation, fatigue peak stress, and multicracking modes on the evolution of interface shear stress and fatigue hysteresis dissipated energy versus cycle numbers curves have been analyzed.

Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity

PubMed Central

Im, Michelle; Dagnino, Lina

2018-01-01

The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults. In ILK-deficient cells, excessive IOS production can be prevented through inhibition of NADPH oxidase activity, with a concomitant reduction in DNA damage. Additionally, ILK is necessary for DNA repair processes following UVB-induced damage, as ILK-deficient cells show a significantly impaired ability to remove cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to maintain cellular redox balance and, in its absence, epidermal cells become more susceptible to oxidative damage through mechanisms that involve IOS production by NADPH oxidase activity. PMID:29568383

Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity.

PubMed

Im, Michelle; Dagnino, Lina

2018-03-02

The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults. In ILK-deficient cells, excessive IOS production can be prevented through inhibition of NADPH oxidase activity, with a concomitant reduction in DNA damage. Additionally, ILK is necessary for DNA repair processes following UVB-induced damage, as ILK-deficient cells show a significantly impaired ability to remove cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to maintain cellular redox balance and, in its absence, epidermal cells become more susceptible to oxidative damage through mechanisms that involve IOS production by NADPH oxidase activity.

Parkin elimination of mitochondria is important for maintenance of lens epithelial cell ROS levels and survival upon oxidative stress exposure.

PubMed

Brennan, Lisa; Khoury, Josef; Kantorow, Marc

2017-01-01

Age-related cataract is associated with oxidative stress and death of lens epithelial cells (LECs) whose survival is dependent on functional mitochondrial populations. Oxidative stress-induced depolarization/damage of LEC mitochondria results in increased reactive oxygen species (ROS) levels and cell death suggesting the need for a LEC mechanism to remove mitochondria depolarized/damaged upon oxidative stress exposure to prevent ROS release and LEC death. To date, a mechanism(s) for removal of depolarized/damaged LEC mitochondria has yet to be identified and the importance of eliminating oxidative stress-damaged mitochondria to prevent LEC ROS release and death has not been established. Here, we demonstrate that Parkin levels increase in LECs exposed to H 2 O 2 -oxidative stress. We establish that Parkin translocates to LEC mitochondria depolarized upon oxidative stress exposure and that Parkin recruits p62/SQSTM1 to depolarized LEC mitochondria. We demonstrate that translocation of Parkin results in the elimination of depolarized/damaged mitochondria and that Parkin clearance of LEC mitochondria is dependent on its ubiquitin ligase activity. Importantly, we demonstrate that Parkin elimination of damaged LEC mitochondria results in reduced ROS levels and increased survival upon oxidative stress exposure. These results establish that Parkin functions to eliminate LEC mitochondria depolarized/damaged upon oxidative stress exposure and that elimination of damaged mitochondria by Parkin is important for LEC homeostasis and survival. The data also suggest that mitochondrial quality control by Parkin could play a role in lens transparency. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Modelling interactions of acid–base balance and respiratory status in the toxicity of metal mixtures in the American oyster Crassostrea virginica

PubMed Central

Macey, Brett M.; Jenny, Matthew J.; Williams, Heidi R.; Thibodeaux, Lindy K.; Beal, Marion; Almeida, Jonas S.; Cunningham, Charles; Mancia, Annalaura; Warr, Gregory W.; Burge, Erin J.; Holland, A. Fred; Gross, Paul S.; Hikima, Sonomi; Burnett, Karen G.; Burnett, Louis; Chapman, Robert W.

2010-01-01

Heavy metals, such as copper, zinc and cadmium, represent some of the most common and serious pollutants in coastal estuaries. In the present study, we used a combination of linear and artificial neural network (ANN) modelling to detect and explore interactions among low-dose mixtures of these heavy metals and their impacts on fundamental physiological processes in tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001–0.400 µM), Zn (0.001–3.059 µM) or Cu (0.002–0.787 µM), either alone or in combination for 1 to 27 days. We measured indicators of acid–base balance (hemolymph pH and total CO2), gas exchange (Po2), immunocompetence (total hemocyte counts, numbers of invasive bacteria), antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative membrane damage from tissue accumulation of environmental metals was correlated with impaired acid–base balance in oysters. ANN analysis revealed interactions of metals with hemolymph acid–base chemistry in predicting oxidative damage that were not evident from linear analyses. These results highlight the usefulness of machine learning approaches, such as ANNs, for improving our ability to recognize and understand the effects of subacute exposure to contaminant mixtures. PMID:19958840

Radiation Effects on the Electrical Properties of Hafnium Oxide Based MOS Capacitors

DTIC Science & Technology

2011-03-01

Figures Figure Page 1. Conceptual illustration of the creation of electron-hole pairs and displacement damage in a n -type silicon metal-oxide-silicon...Illustration of the effect, in a CV plot, of oxide trapped charge for a hypothetical n -type device...8 5. Illustration of the effect, in a CV plot, of interface trapped charge for a hypothetical n -type device

Cold atmospheric-pressure plasma induces DNA-protein crosslinks through protein oxidation.

PubMed

Guo, Li; Zhao, Yiming; Liu, Dingxin; Liu, Zhichao; Chen, Chen; Xu, Ruobing; Tian, Miao; Wang, Xiaohua; Chen, Hailan; Kong, Michael G

2018-05-03

Reactive oxygen and nitrogen species (ROS and RNS) generated by cold atmospheric-pressure plasma could damage genomic DNA, although the precise type of these DNA damage induced by plasma are poorly characterized. Understanding plasma-induced DNA damage will help to elucidate the biological effect of plasma and guide the application of plasma in ROS-based therapy. In this study, it was shown that ROS and RNS generated by physical plasma could efficiently induce DNA-protein crosslinks (DPCs) in bacteria, yeast, and human cells. An in vitro assay showed that plasma treatment resulted in the formation of covalent DPCs by activating proteins to crosslink with DNA. Mass spectrometry and hydroperoxide analysis detected oxidation products induced by plasma. DPC formation were alleviated by singlet oxygen scavenger, demonstrating the importance of singlet oxygen in this process. These results suggested the roles of DPC formation in DNA damage induced by plasma, which could improve the understanding of the biological effect of plasma and help to develop a new strategy in plasma-based therapy including infection and cancer therapy.

Chronic Obstructive Pulmonary Disease: From Injury to Genomic Stability.

PubMed

Sergio, Luiz Philippe da Silva; de Paoli, Flavia; Mencalha, Andre Luiz; da Fonseca, Adenilson de Souza

2017-08-01

Chronic obstructive pulmonary disease (COPD) is the fourth cause of death in the world and it is currently presenting a major global public health challenge, causing premature death from pathophysiological complications and rising economic and social burdens. COPD develops from a combination of factors following exposure to pollutants and cigarette smoke, presenting a combination of both emphysema and chronic obstructive bronchitis, which causes lung airflow limitations that are not fully reversible by bronchodilators. Oxidative stress plays a key role in the maintenance and amplification of inflammation in tissue injury, and also induces DNA damages. Once the DNA molecule is damaged, enzymatic mechanisms act in order to repair the DNA molecule. These mechanisms are specific to repair of oxidative damages, such as nitrogen base modifications, or larger DNA damages, such as double-strand breaks. In addition, there is an enzymatic mechanism for the control of telomere length. All these mechanisms contribute to cell viability and homeostasis. Thus, therapies based on modulation of DNA repair and genomic stability could be effective in improving repair and recovery of lung tissue in patients with COPD.

Flies, worms and the Free Radical Theory of ageing.

PubMed

Clancy, David; Birdsall, John

2013-01-01

Drosophila and Caenorhabditis elegans have provided the largest body of evidence addressing the Free Radical Theory of ageing, however the evidence has not been unequivocally supportive. Oxidative damage to DNA is probably not a major contributor, damage to lipids is assuming greater importance and damage to proteins probably the source of pathology. On balance the evidence does not support a primary role of oxidative damage in ageing in C. elegans, perhaps because of its particular energy metabolic and stress resistance profile. Evidence is more numerous, varied and consistent and hence more compelling for Drosophila, although not conclusive. However there is good evidence for a role of oxidative damage in later life pathology. Future work should: 1/ make more use of protein oxidative damage measurements; 2/ use inducible transgenic systems or pharmacotherapy to ensure genetic equivalence of controls and avoid confounding effects during development; 3/ to try to delay ageing, target interventions which reduce and/or repair protein oxidative damage. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Oxidative stress and mitochondrial damage in coronary artery bypass graft surgery: effects of antioxidant treatments.

PubMed

Milei, J; Ferreira, R; Grana, D R; Boveris, A

2001-01-01

We examined antioxidant actions in 73 patients undergoing coronary artery surgery by assessing mitochondrial damage and oxidative stress in ventricular biopsies obtained at preischemia and postreperfusion. Those patients who received antioxidant therapy benefited by less oxidative stress and mitochondrial damage.

Pro-oxidant Induced DNA Damage in Human Lymphoblastoid Cells: Homeostatic Mechanisms of Genotoxic Tolerance

PubMed Central

Seager, Anna L.

2012-01-01

Oxidative stress contributes to many disease etiologies including ageing, neurodegeneration, and cancer, partly through DNA damage induction (genotoxicity). Understanding the i nteractions of free radicals with DNA is fundamental to discern mutation risks. In genetic toxicology, regulatory authorities consider that most genotoxins exhibit a linear relationship between dose and mutagenic response. Yet, homeostatic mechanisms, including DNA repair, that allow cells to tolerate low levels of genotoxic exposure exist. Acceptance of thresholds for genotoxicity has widespread consequences in terms of understanding cancer risk and regulating human exposure to chemicals/drugs. Three pro-oxidant chemicals, hydrogen peroxide (H2O2), potassium bromate (KBrO3), and menadione, were examined for low dose-response curves in human lymphoblastoid cells. DNA repair and antioxidant capacity were assessed as possible threshold mechanisms. H2O2 and KBrO3, but not menadione, exhibited thresholded responses, containing a range of nongenotoxic low doses. Levels of the DNA glycosylase 8-oxoguanine glycosylase were unchanged in response to pro- oxidant stress. DNA repair–focused gene expression arrays reported changes in ATM and BRCA1, involved in double-strand break repair, in response to low-dose pro-oxidant exposure; however, these alterations were not substantiated at the protein level. Determination of oxidatively induced DNA damage in H2O2-treated AHH-1 cells reported accumulation of thymine glycol above the genotoxic threshold. Further, the H2O2 dose-response curve was shifted by modulating the antioxidant glutathione. Hence, observed pro- oxidant thresholds were due to protective capacities of base excision repair enzymes and antioxidants against DNA damage, highlighting the importance of homeostatic mechanisms in “genotoxic tolerance.” PMID:22539617

Oxidative shielding and the cost of reproduction.

PubMed

Blount, Jonathan D; Vitikainen, Emma I K; Stott, Iain; Cant, Michael A

2016-05-01

Life-history theory assumes that reproduction and lifespan are constrained by trade-offs which prevent their simultaneous increase. Recently, there has been considerable interest in the possibility that this cost of reproduction is mediated by oxidative stress. However, empirical tests of this theory have yielded equivocal support. We carried out a meta-analysis to examine associations between reproduction and oxidative damage across markers and tissues. We show that oxidative damage is positively associated with reproductive effort across females of various species. Yet paradoxically, categorical comparisons of breeders versus non-breeders reveal that transition to the reproductive state is associated with a step-change reduction in oxidative damage in certain tissues and markers. Developing offspring may be particularly sensitive to harm caused by oxidative damage in mothers. Therefore, such reductions could potentially function to shield reproducing mothers, gametes and developing offspring from oxidative insults that inevitably increase as a consequence of reproductive effort. According to this perspective, we hypothesise that the cost of reproduction is mediated by dual impacts of maternally-derived oxidative damage on mothers and offspring, and that mothers may be selected to diminish such damage. Such oxidative shielding may explain why many existing studies have concluded that reproduction has little or no oxidative cost. Future advance in life-history theory therefore needs to take account of potential transgenerational impacts of the mechanisms underlying life-history trade-offs. © 2015 Cambridge Philosophical Society.

Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteins.

PubMed

O'Rourke, Thomas W; Doudican, Nicole A; Mackereth, Melinda D; Doetsch, Paul W; Shadel, Gerald S

2002-06-01

The mitochondrial genome is a significant target of exogenous and endogenous genotoxic agents; however, the determinants that govern this susceptibility and the pathways available to resist mitochondrial DNA (mtDNA) damage are not well characterized. Here we report that oxidative mtDNA damage is elevated in strains lacking Ntg1p, providing the first direct functional evidence that this mitochondrion-localized, base excision repair enzyme functions to protect mtDNA. However, ntg1 null strains did not exhibit a mitochondrial respiration-deficient (petite) phenotype, suggesting that mtDNA damage is negotiated by the cooperative actions of multiple damage resistance pathways. Null mutations in ABF2 or PIF1, two genes implicated in mtDNA maintenance and recombination, exhibit a synthetic-petite phenotype in combination with ntg1 null mutations that is accompanied by enhanced mtDNA point mutagenesis in the corresponding double-mutant strains. This phenotype was partially rescued by malonic acid, indicating that reactive oxygen species generated by the electron transport chain contribute to mitochondrial dysfunction in abf2 Delta strains. In contrast, when two other genes involved in mtDNA recombination, CCE1 and NUC1, were inactivated a strong synthetic-petite phenotype was not observed, suggesting that the effects mediated by Abf2p and Pif1p are due to novel activities of these proteins other than recombination. These results document the existence of recombination-independent mechanisms in addition to base excision repair to cope with oxidative mtDNA damage in Saccharomyces cerevisiae. Such systems are likely relevant to those operating in human cells where mtDNA recombination is less prevalent, validating yeast as a model system in which to study these important issues.

Effects of oxidative stress-induced changes in the actin cytoskeletal structure on myoblast damage under compressive stress: confocal-based cell-specific finite element analysis.

PubMed

Yao, Yifei; Lacroix, Damien; Mak, Arthur F T

2016-12-01

Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myoblasts and presented a finite element (FE) analysis of how such changes in the actin cytoskeletal structure affected a myoblast's capability to resist damage under compression. A confocal-based cell-specific FE model was built to parametrically study the effects of stress fiber density, fiber cross-sectional area, fiber tensile prestrain, as well as the elastic moduli of the stress fibers, actin cortex, nucleus and cytoplasm. The results showed that a decrease in the elastic moduli of both the stress fibers and actin cortex could increase the average tensile strain on the actin cortex-membrane structure and reduce the apparent cell elastic modulus. Assuming the cell would die when a certain percentage of membrane elements were strained beyond a threshold, a lower elastic modulus of actin cytoskeleton would compromise the compressive resistance of a myoblast and lead to cell death more readily. This model was used with a Weibull distribution function to successfully describe the extent of myoblasts damaged in a monolayer under compression.

Effects of exercise on markers of oxidative stress: an Ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention Trial

PubMed Central

Friedenreich, Christine M; Pialoux, Vincent; Wang, Qinggang; Shaw, Eileen; Brenner, Darren R; Waltz, Xavier; Conroy, Shannon M; Johnson, Rhys; Woolcott, Christy G; Poulin, Marc J; Courneya, Kerry S

2016-01-01

Background Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women. Methods The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50–74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed. Results In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity. Conclusions A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women. Trial registration number NCT00522262. PMID:27900199

Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

PubMed

Moruno-Manchon, Jose F; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

2018-01-01

Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general. Copyright © 2017 Elsevier Inc. All rights reserved.

CD44-targeted hyaluronic acid-curcumin prodrug protects renal tubular epithelial cell survival from oxidative stress damage.

PubMed

Hu, Jing-Bo; Li, Shu-Juan; Kang, Xu-Qi; Qi, Jing; Wu, Jia-Hui; Wang, Xiao-Juan; Xu, Xiao-Ling; Ying, Xiao-Ying; Jiang, Sai-Ping; You, Jian; Du, Yong-Zhong

2018-08-01

Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H 2 O 2 -pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors. Biodistribution results further demonstrated the increased accumulation of HA-CUR in kidneys with 13.9-fold higher than that of free CUR. Pharmacodynamic studies indicated HA-CUR effectively ameliorated AKI, and the exact mechanism was that HA-CUR protected renal tubule epithelial cells from oxidative stress damage via inhibiting PtdIns3K-AKT-mTOR signaling pathway. Taken together, this study provides a new therapeutic strategy for the treatment of AKI based on the pathogenesis of the disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative analysis of the relative potential of silver, zinc-oxide and titanium-dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin carcinogenesis

PubMed Central

Arora, Sumit; Omar, Yousef; Ijaz, Zohaib Mohammad; AL-Ghadhban, Ahmed; Deshmukh, Sachin K.; Carter, James E.; Singh, Ajay P.; Singh, Seema

2016-01-01

Sunscreen formulations containing UVB filters, such as Zinc-oxide (ZnO) and titanium-dioxide (TiO2) nanoparticles (NPs) have been developed to limit the exposure of human skin to UV-radiations. Unfortunately, these UVB protective agents have failed in controlling the skin cancer incidence. We recently demonstrated that silver nanoparticles (Ag-NPs) could serve as novel protective agents against UVB-radiations. Here our goal was to perform comparative analysis of direct and indirect UVB-protection efficacy of ZnO-, TiO2- and Ag-NPs. Sun-protection-factor calculated based on their UVB-reflective/absorption abilities was the highest for TiO2-NPs followed by Ag- and ZnO-NPs. This was further confirmed by studying indirect protection of UVB radiation-induced death of HaCaT cells. However, only Ag-NPs were active in protecting HaCaT cells against direct UVB-induced DNA-damage by repairing bulky-DNA lesions through nucleotide-excision-repair mechanism. Moreover, Ag-NPs were also effective in protecting HaCaT cells from UVB-induced oxidative DNA damage by enhancing SOD/CAT/GPx activity. In contrast, ZnO- and TiO2-NPs not only failed in providing any direct protection from DNA-damage, but rather enhanced oxidative DNA-damage by increasing ROS production. Together, these findings raise concerns about safety of ZnO- and TiO2-NPs and establish superior protective efficacy of Ag-NPs. PMID:27693632

Chlorpyrifos-induced oxidative damage is reduced under warming and predation risk: Explaining antagonistic interactions with a pesticide.

PubMed

Janssens, Lizanne; Stoks, Robby

2017-07-01

Interactions with pollutants and environmental factors are poorly studied for physiological traits. Yet physiological traits are important for explaining and predicting interactions at higher levels of organization. We investigated the single and combined impact of the pesticide chlorpyrifos, predation risk and warming on endpoints related to oxidative stress in the damselfly Enallagma cyathigerum. We thereby integrated information on reactive oxygen species (ROS), antioxidant enzymes and oxidative damage. All three treatments impacted the oxidative stress levels and for most traits the pesticide interacted antagonistically with warming or predation risk. Chlorpyrifos exposure resulted in increased ROS levels, decreased antioxidant defence and increased oxidative damage compared to the control situation. Under warming, the pesticide-induced increase in oxidative stress was less strong and the investment in antioxidant defence higher. Although both the pesticide and predation risk increased oxidative damage, the effects of the pesticide on oxidative damage were less strong in the presence of predator cues (at 20 °C). Despite the weaker pesticide-induced effects under predation risk, the combination of the pesticide and predator cues consistently caused the highest ROS levels, the lowest antioxidant defence and the highest oxidative damage, indicating the importance of cumulative stressor effects for impairing fitness. Our results provide the first evidence for antagonistic interactions of warming and predation risk with a pollutant for physiological traits. We identified two general mechanisms that may generate antagonistic interactions for oxidative stress: cross-tolerance and the maximum cumulative levels of damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-05-06

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

Impact of Hot Environment on Fluid and Electrolyte Imbalance, Renal Damage, Hemolysis, and Immune Activation Postmarathon

PubMed Central

Oliveira, Rodrigo Assunção; Sierra, Ana Paula Rennó; Benetti, Marino; Ghorayeb, Nabil; Sierra, Carlos A.; Kiss, Maria Augusta Peduti Dal Molin

2017-01-01

Previous studies have demonstrated the physiological changes induced by exercise exposure in hot environments. We investigated the hematological and oxidative changes and tissue damage induced by marathon race in different thermal conditions. Twenty-six male runners completed the São Paulo International Marathon both in hot environment (HE) and in temperate environment (TE). Blood and urine samples were collected 1 day before, immediately after, 1 day after, and 3 days after the marathon to analyze the hematological parameters, electrolytes, markers of tissue damage, and oxidative status. In both environments, the marathon race promotes fluid and electrolyte imbalance, hemolysis, oxidative stress, immune activation, and tissue damage. The marathon runner's performance was approximately 13.5% lower in HE compared to TE; however, in HE, our results demonstrated more pronounced fluid and electrolyte imbalance, renal damage, hemolysis, and immune activation. Moreover, oxidative stress induced by marathon in HE is presumed to be related to protein/purine oxidation instead of other oxidative sources. Fluid and electrolyte imbalance and protein/purine oxidation may be important factors responsible for hemolysis, renal damage, immune activation, and impaired performance after long-term exercise in HE. Nonetheless, we suggested that the impairment on performance in HE was not associated to the muscle damage and lipoperoxidation. PMID:29430287

Protections of bovine serum albumin protein from damage on functionalized graphene-based electrodes by flavonoids.

PubMed

Sun, Bolu; Gou, Yuqiang; Xue, Zhiyuan; Zheng, Xiaoping; Ma, Yuling; Hu, Fangdi; Zhao, Wanghong

2016-05-01

A sensitive electrochemical sensor based on bovine serum albumin (BSA)/poly (diallyldimethylammonium chloride) (PDDA) functionalized graphene nanosheets (PDDA-G) composite film modified glassy carbon electrode (BSA/PDDA-G/GCE) had been developed to investigate the oxidative protein damage and protections of protein from damage by flavonoids. The performance of this sensor was remarkably improved due to excellent electrical conductivity, strong adsorptive ability, and large effective surface area of PDDA-G. The BSA/PDDA-G/GCE displayed the greatest degree of BSA oxidation damage at 40 min incubation time and in the pH 5.0 Fenton reagent system (12.5 mM FeSO4, 50 mM H2O2). The antioxidant activities of four flavonoids had been compared by fabricated sensor based on the relative peak current ratio of SWV, because flavonoids prevented BSA damage caused by Fenton reagent and affected the BSA signal in a solution containing Co(bpy)3(3+). The sensor was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). UV-vis spectrophotometry and FTIR were also used to investigate the generation of hydroxyl radical and BSA damage, respectively. On the basis of results from electrochemical methods, the order of the antioxidant activities of flavonoids is as follows: (+)-catechin>kaempferol>apigenin>naringenin. A novel, direct SWV analytical method for detection of BSA damage and assessment of the antioxidant activities of four flavonoids was developed and this electrochemical method provided a simple, inexpensive and rapid detection of BSA damage and evaluation of the antioxidant activities of samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3β signaling.

PubMed

Baek, Sang-Min; Yu, Seung-Young; Son, Youngsook; Hong, Hyun Sook

2016-01-01

Senescence of the retina causes an accumulation of reactive oxygen species (ROS). Oxidative stress associated with ROS can damage RPE cells, leading to neovascularization and severe ocular disorders, including age-related macular degeneration (AMD). Thus, the early treatment of the damage caused by oxidative stress is critical for preventing the development of ocular diseases such as AMD. In this study, we examined the role of substance P (SP) in the recovery of RPE cells damaged by oxidative stress. To induce oxidative stress, RPE cells were treated with H2O2 at various doses. Recovery from oxidative stress was studied following treatment with SP by analyzing cell viability, cell proliferation, cell apoptosis, and Akt/glycogen synthase kinase (GSK)-3β activation in RPE cells in vitro. H2O2 treatment reduced cellular viability in a dose-dependent manner. SP inhibited the reduction of cell viability due to H2O2 and caused increased cell proliferation and decreased cell apoptosis. Cell survival under oxidative stress requires the activation of Akt signaling that enables cells to resist oxidative stress-induced damage. SP treatment activated Akt/GSK-3β signaling in RPE cells, which were damaged due to oxidative stress, and the inhibition of Akt signaling in SP-treated RPE cells prevented SP-induced recovery. Pretreatment with the neurokinin 1 receptor (NK1R) antagonist reduced the recovery effect of SP on damaged RPE cells. SP can protect RPE cells from oxidant-induced cell death by activating Akt/GSK-3β signaling via NK1R. This study suggests the possibility of SP as a treatment for oxidative stress-related diseases.

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

PubMed

Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

2017-06-18

Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress

PubMed Central

Wilson, Andrew F.; Li, Xue

2017-01-01

ABSTRACT Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G2/M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress. PMID:28475398

Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells.

PubMed

Poletto, Mattia; Yang, Di; Fletcher, Sally C; Vendrell, Iolanda; Fischer, Roman; Legrand, Arnaud J; Dianov, Grigory L

2017-09-29

Ataxia telangiectasia (A-T) is a syndrome associated with loss of ATM protein function. Neurodegeneration and cancer predisposition, both hallmarks of A-T, are likely to emerge as a consequence of the persistent oxidative stress and DNA damage observed in this disease. Surprisingly however, despite these severe features, a lack of functional ATM is still compatible with early life, suggesting that adaptation mechanisms contributing to cell survival must be in place. Here we address this gap in our knowledge by analysing the process of human fibroblast adaptation to the lack of ATM. We identify profound rearrangement in cellular proteostasis occurring very early on after loss of ATM in order to counter protein damage originating from oxidative stress. Change in proteostasis, however, is not without repercussions. Modulating protein turnover in ATM-depleted cells also has an adverse effect on the DNA base excision repair pathway, the major DNA repair system that deals with oxidative DNA damage. As a consequence, the burden of unrepaired endogenous DNA lesions intensifies, progressively leading to genomic instability. Our study provides a glimpse at the cellular consequences of loss of ATM and highlights a previously overlooked role for proteostasis in maintaining cell survival in the absence of ATM function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Constraint and cost of oxidative stress on reproduction: correlative evidence in laboratory mice and review of the literature

PubMed Central

2012-01-01

Background One central concept in evolutionary ecology is that current and residual reproductive values are negatively linked by the so-called cost of reproduction. Previous studies examining the nature of this cost suggested a possible involvement of oxidative stress resulting from the imbalance between pro- and anti-oxidant processes. Still, data remain conflictory probably because, although oxidative damage increases during reproduction, high systemic levels of oxidative stress might also constrain parental investment in reproduction. Here, we investigated variation in oxidative balance (i.e. oxidative damage and antioxidant defences) over the course of reproduction by comparing female laboratory mice rearing or not pups. Results A significant increase in oxidative damage over time was only observed in females caring for offspring, whereas antioxidant defences increased over time regardless of reproductive status. Interestingly, oxidative damage measured prior to reproduction was negatively associated with litter size at birth (constraint), whereas damage measured after reproduction was positively related to litter size at weaning (cost). Conclusions Globally, our correlative results and the review of literature describing the links between reproduction and oxidative stress underline the importance of timing/dynamics when studying and interpreting oxidative balance in relation to reproduction. Our study highlights the duality (constraint and cost) of oxidative stress in life-history trade-offs, thus supporting the theory that oxidative stress plays a key role in life-history evolution. PMID:23268929

Effects of Hydrogen Peroxide on Wound Healing in Mice in Relation to Oxidative Damage

PubMed Central

Ho, Rongjian; Wasser, Martin; Du, Tiehua; Ng, Wee Thong; Halliwell, Barry

2012-01-01

It has been established that low concentrations of hydrogen peroxide (H2O2) are produced in wounds and is required for optimal healing. Yet at the same time, there is evidence that excessive oxidative damage is correlated with poor-healing wounds. In this paper, we seek to determine whether topical application of H2O2 can modulate wound healing and if its effects are related to oxidative damage. Using a C57BL/6 mice excision wound model, H2O2 was found to enhance angiogenesis and wound closure at 10 mM but retarded wound closure at 166 mM. The delay in closure was also associated with decreased connective tissue formation, increased MMP-8 and persistent neutrophil infiltration. Wounding was found to increase oxidative lipid damage, as measured by F2-isoprostanes, and nitrative protein damage, as measured by 3-nitrotyrosine. However H2O2 treatment did not significantly increase oxidative and nitrative damage even at concentrations that delay wound healing. Hence the detrimental effects of H2O2 may not involve oxidative damage to the target molecules studied. PMID:23152875

Dietary antioxidants, lipid peroxidation and plumage colouration in nestling blue tits Cyanistes caeruleus

NASA Astrophysics Data System (ADS)

Larcombe, Stephen D.; Mullen, William; Alexander, Lucille; Arnold, Kathryn E.

2010-10-01

Carotenoid pigments are responsible for many of the red, yellow and orange plumage and integument traits seen in birds. One idea suggests that since carotenoids can act as antioxidants, carotenoid-mediated colouration may reveal an individual's ability to resist oxidative damage. In fact, there is currently very little information on the effects of most dietary-acquired antioxidants on oxidative stress in wild birds. Here, we assessed the impacts on oxidative damage, plasma antioxidants, growth and plumage colouration after supplementing nestling blue tits Cyanistes caeruleus with one of three diets; control, carotenoid treatment or α-tocopherol treatment. Oxidative damage was assessed by HPLC analysis of plasma levels of malondialdehyde (MDA), a by-product of lipid peroxidation. Contrary to predictions, we found no differences in oxidative damage, plumage colouration or growth rate between treatment groups. Although plasma lutein concentrations were significantly raised in carotenoid-fed chicks, α-tocopherol treatment had no effect on concentrations of plasma α-tocopherol compared with controls. Interestingly, we found that faster growing chicks had higher levels of oxidative damage than slower growing birds, independent of treatment, body mass and condition at fledging. Moreover, the chromatic signal of the chest plumage of birds was positively correlated with levels of MDA but not plasma antioxidant concentrations: more colourful nestlings had higher oxidative damage than less colourful individuals. Thus, increased carotenoid-mediated plumage does not reveal resistance to oxidative damage for nestling blue tits, but may indicate costs paid, in terms of oxidative damage. Our results indicate that the trade-offs between competing physiological systems for dietary antioxidants are likely to be complex in rapidly developing birds. Moreover, interpreting the biological relevance of different biomarkers of antioxidant status represents a challenge for evolutionary ecology.

Development of HSPA1A promoter-driven luciferase reporter gene assays in human cells for assessing the oxidative damage induced by silver nanoparticles.

PubMed

Xin, Lili; Wang, Jianshu; Zhang, Leshuai W; Che, Bizhong; Dong, Guangzhu; Fan, Guoqiang; Cheng, Kaiming

2016-08-01

The exponential increase in the total number of engineered nanoparticles in consumer products requires novel tools for rapid and cost-effective toxicology screening. In order to assess the oxidative damage induced by nanoparticles, toxicity test systems based on a human HSPA1A promoter-driven luciferase reporter in HepG2, LO2, A549, and HBE cells were established. After treated with heat shock and a group of silver nanoparticles (AgNPs) with different primary particle sizes, the cell viability, oxidative damage, and luciferase activity were determined. The time-dependent Ag(+) ions release from AgNPs in cell medium was also evaluated. Our results showed that heat shock produced a strong time-dependent induction of relative luciferase activity in the four luciferase reporter cells. Surprisingly, at 4h of recovery, the relative luciferase activity was >98× the control level in HepG2-luciferase cells. Exposure to different sizes of AgNPs resulted in activation of the HSPA1A promoter in a dose-dependent manner, even at low cytotoxic or non-cytotoxic doses. The smaller (5nm) AgNPs were more potent in luciferase induction than the larger (50 and 75nm) AgNPs. These results were generally in accordance with the oxidative damage indicated by malondialdehyde concentration, reactive oxygen species induction and glutathione depletion, and Ag(+) ions release in cell medium. Compared with the other three luciferase reporter cells, the luciferase signal in HepG2-luciferase cells is obviously more sensitive and stable. We conclude that the luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the oxidative damage induced by AgNPs. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of DNA damage in a group of professional dancers during a 10-month dancing season.

PubMed

Esteves, Filipa; Teixeira, Eduardo; Amorim, Tânia; Costa, Carla; Pereira, Cristiana; Fraga, Sónia; De Andrade, Vanessa Moraes; Teixeira, João Paulo; Costa, Solange

2017-01-01

Despite the numerous health benefits of physical activity, some studies reported that increased intensity and duration may induce oxidative stress in several cellular components including DNA. The aim of this study was to assess the level of basal DNA damage as well as oxidative DNA damage in a group of professional dancers before and after a 10-month dancing season. A group of individuals from general population was also assessed as a control. The alkaline version of the comet assay was the method selected to measure both basal DNA damage and oxidative stress, since this method quantifies both endpoints. In order to measure oxidative stress, the comet assay was coupled with a lesion-specific endonuclease (formamidopyrimidine glycosylase) to detect oxidized purines. The levels of oxidative DNA damage in dancers were significantly increased after the dancing season. Pre-season levels of oxidative DNA damage were lower in dancers than those obtained from the general population, suggesting an adaptation of antioxidant system in dancers. Results of the present biomonitoring study indicate the need for more effective measures to protect ballet dancers from potentially occupational health risks related to regular intensive physical exercise.

Insight into the structure and mechanism of nickel-containing superoxide dismutase derived from peptide-based mimics.

PubMed

Shearer, Jason

2014-08-19

Nickel superoxide dismutase (NiSOD) is a nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide through a ping-pong mechanism that relies on accessing reduced Ni(II) and oxidized Ni(III) oxidation states. NiSOD is the most recently discovered SOD. Unlike the other known SODs (MnSOD, FeSOD, and (CuZn)SOD), which utilize "typical" biological nitrogen and oxygen donors, NiSOD utilizes a rather unexpected ligand set. In the reduced Ni(II) oxidation state, NiSOD utilizes nitrogen ligands derived from the N-terminal amine and an amidate along with two cysteinates sulfur donors. These are unusual biological ligands, especially for an SOD: amine and amidate donors are underrepresented as biological ligands, whereas cysteinates are highly susceptible to oxidative damage. An axial histidine imidazole binds to nickel upon oxidation to Ni(III). This bond is long (2.3-2.6 Å) owing to a tight hydrogen-bonding network. All of the ligating residues to Ni(II) and Ni(III) are found within the first 6 residues from the NiSOD N-terminus. Thus, small nickel-containing metallopeptides derived from the first 6-12 residues of the NiSOD sequence can reproduce many of the properties of NiSOD itself. Using these nickel-containing metallopeptide-based NiSOD mimics, we have shown that the minimal sequence needed for nickel binding and reproduction of the structural, spectroscopic, and functional properties of NiSOD is H2N-HCXXPC. Insight into how NiSOD avoids oxidative damage has also been gained. Using small NiN2S2 complexes and metallopeptide-based mimics, it was shown that the unusual nitrogen donor atoms protect the cysteinates from oxidative damage (both one-electron oxidation and oxygen atom insertion reactions) by fine-tuning the electronic structure of the nickel center. Changing the nitrogen donor set to a bis-amidate or bis-amine nitrogen donor led to catalytically nonviable species owing to nickel-cysteinate bond oxidative damage. Only the amine/amidate nitrogen donor atoms within the NiSOD ligand set produce a catalytically viable species. These metallopeptide-based mimics have also hinted at the detailed mechanism of SOD catalysis by NiSOD. One such aspect is that the axial imidazole likely remains ligated to the Ni center under rapid catalytic conditions (i.e., high superoxide loads). This reduces the degree of structural rearrangement about the nickel center, leading to higher catalytic rates. Metallopeptide-based mimics have also shown that, although an axial ligand to Ni(III) is required for catalysis, the rates are highest when this is a weak interaction, suggesting a reason for the long axial His-Ni(III) bond found in NiSOD. These mimics have also suggested a surprising mechanistic insight: O2(-) reduction via a "H(•)" tunneling event from a R-S(H(+))-Ni(II) moiety to O2(-) is possible. The importance of this mechanism in NiSOD has not been verified.

Selectivity of protein oxidative damage during aging in Drosophila melanogaster.

PubMed Central

Das, N; Levine, R L; Orr, W C; Sohal, R S

2001-01-01

The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions. PMID:11696009

Effect of complex polyphenols and tannins from red wine on DNA oxidative damage of rat colon mucosa in vivo.

PubMed

Giovannelli, L; Testa, G; De Filippo, C; Cheynier, V; Clifford, M N; Dolara, P

2000-10-01

Dietary polyphenols have been reported to have a variety of biological actions, including anti-carcinogenic, antioxidant and anti-inflammatory activities. In the present study we have evaluated the effect of an oral treatment with complex polyphenols and tannins from red wine and tea on DNA oxidative damage in the rat colon mucosa. Isolated colonocytes were prepared from the colon mucosa of rats treated for ten days with either wine complex polyphenols (57.2 mg/kg/d) or thearubigin (40 mg/kg/d) by oral gavage. Colonocyte oxidative DNA damage was analysed at the single cell level using a modification of the comet assay technique. The results show that wine complex polyphenols and tannins induce a significant decrease (-62% for pyrimidine and -57% for purine oxidation) in basal DNA oxidative damage in colon mucosal cells without affecting the basal level of single-strand breaks. On the other hand, tea polyphenols, namely a crude extract of thearubigin, did not affect either strand breaks or pyrimidine oxidation in colon mucosal cells. Our experiments are the first demonstration that dietary polyphenols can modulate in vivo oxidative damage in the gastrointestinal tract of rodents. These data support the hypothesis that dietary polyphenols might have both a protective and a therapeutic potential in oxidative damage-related pathologies.

MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good?

PubMed

Abbas, Hussein H K; Alhamoudi, Kheloud M H; Evans, Mark D; Jones, George D D; Foster, Steven S

2018-04-16

Targeted therapies are based on exploiting cancer-cell-specific genetic features or phenotypic traits to selectively kill cancer cells while leaving normal cells unaffected. Oxidative stress is a cancer hallmark phenotype. Given that free nucleotide pools are particularly vulnerable to oxidation, the nucleotide pool sanitising enzyme, MTH1, is potentially conditionally essential in cancer cells. However, findings from previous MTH1 studies have been contradictory, meaning the relevance of MTH1 in cancer is still to be determined. Here we ascertained the role of MTH1 specifically in lung cancer cell maintenance, and the potential of MTH1 inhibition as a targeted therapy strategy to improve lung cancer treatments. Using siRNA-mediated knockdown or small-molecule inhibition, we tested the genotoxic and cytotoxic effects of MTH1 deficiency on H23 (p53-mutated), H522 (p53-mutated) and A549 (wildtype p53) non-small cell lung cancer cell lines relative to normal MRC-5 lung fibroblasts. We also assessed if MTH1 inhibition augments current therapies. MTH1 knockdown increased levels of oxidatively damaged DNA and DNA damage signaling alterations in all lung cancer cell lines but not normal fibroblasts, despite no detectable differences in reactive oxygen species levels between any cell lines. Furthermore, MTH1 knockdown reduced H23 cell proliferation. However, unexpectedly, it did not induce apoptosis in any cell line or enhance the effects of gemcitabine, cisplatin or radiation in combination treatments. Contrastingly, TH287 and TH588 MTH1 inhibitors induced apoptosis in H23 and H522 cells, but only increased oxidative DNA damage levels in H23, indicating that they kill cells independently of DNA oxidation and seemingly via MTH1-distinct mechanisms. MTH1 has a NSCLC-specific p53-independent role for suppressing DNA oxidation and genomic instability, though surprisingly the basis of this may not be reactive-oxygen-species-associated oxidative stress. Despite this, overall our cell viability data indicates that targeting MTH1 will likely not be an across-the-board effective NSCLC therapeutic strategy; rather it induces non-cytotoxic DNA damage that could promote cancer heterogeneity and evolution.

DNA Repair Deficiency in Neurodegeneration

PubMed Central

Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A.; Stevnsner, Tinna

2011-01-01

Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby causing Huntington’s disease. Single-strand breaks are common DNA lesions and are associated with the neurodegenerative diseases, ataxia-oculomotor apraxia-1 and spinocerebellar ataxia with axonal neuropathy-1. DNA double-strand breaks are toxic lesions and two main pathways exist for their repair: homologous recombination and non-homologous end-joining. Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage may be linked with the age-associated neurodegenerative disorders Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Mutation in the WRN protein leads to the premature aging disease Werner syndrome, a disorder that features neurodegeneration. In this article we review the evidence linking deficiencies in the DNA repair pathways with neurodegeneration. PMID:21550379

Hawkmoths use nectar sugar to reduce oxidative damage from flight.

PubMed

Levin, E; Lopez-Martinez, G; Fane, B; Davidowitz, G

2017-02-17

Nectar-feeding animals have among the highest recorded metabolic rates. High aerobic performance is linked to oxidative damage in muscles. Antioxidants in nectar are scarce to nonexistent. We propose that nectarivores use nectar sugar to mitigate the oxidative damage caused by the muscular demands of flight. We found that sugar-fed moths had lower oxidative damage to their flight muscle membranes than unfed moths. Using respirometry coupled with δ 13 C analyses, we showed that moths generate antioxidant potential by shunting nectar glucose to the pentose phosphate pathway (PPP), resulting in a reduction in oxidative damage to the flight muscles. We suggest that nectar feeding, the use of PPP, and intense exercise are causally linked and have allowed the evolution of powerful fliers that feed on nectar. Copyright © 2017, American Association for the Advancement of Science.

An acetyl-L-carnitine switch on mitochondrial dysfunction and rescue in the metabolomics study on aluminum oxide nanoparticles.

PubMed

Li, Xiaobo; Zhang, Chengcheng; Zhang, Xin; Wang, Shizhi; Meng, Qingtao; Wu, Shenshen; Yang, Hongbao; Xia, Yankai; Chen, Rui

2016-01-16

Due to the wide application of engineered aluminum oxide nanoparticles and increased aluminum containing particulate matter suspending in air, exposure of human to nano-scale aluminum oxide nanoparticles (Al2O3 NPs) is becoming inevitable. In the present study, RNA microarray coupled with metabolomics analysis were used to uncover mechanisms underlying cellular responses to Al2O3 NPs and imply the potential rescue. We found that Al2O3 NPs significantly triggered down-regulation of mitochondria-related genes located in complex I, IV and V, which were involved in oxidative phosphorylation and neural degeneration pathways, in human bronchial epithelial (HBE) cells. Subsequent cell- and animal- based assays confirmed that Al2O3 NPs caused mitochondria-dependent apoptosis and oxidative stress either in vitro or in vivo, which were consistent with the trends of gene regulation. To rescue the Al2O3 NPs induced mitochondria dysfunction, disruption of small molecular metabolites of HBE were profiled using metabolomics analysis, which facilitates identification of potential antagonizer or supplement against nanoparticle-involved damages. Supplementation of an antioxidant, acetyl-L-carnitine, completely or partially restored the Al2O3 NPs modulated gene expression levels in mitochondrial complex I, IV and V. It further reduced apoptosis and oxidative damages in both Al2O3 NPs treated HBE cells and animal lung tissues. Thus, our results demonstrate the potential mechanism of respiratory system damages induced by Al2O3 NPs. Meanwhile, based on the metabolomics profiling, application of acetyl-L-carnitine is suggested to ameliorate mitochondria dysfunction associated with Al2O3 NPs.

Interaction between alpha and upsilon-crystallin, common to the eye of the Australian platypus, by radical probe mass spectrometry.

PubMed

Issa, Samah; Downard, Kevin M

2006-10-01

The interaction between alpha-crystallin and upsilon-crystallin, a class recently discovered in the eye of the Australian platypus, has been shown by native shift gel assay and examined by radical probe mass spectrometry in the context of the ability of alpha-crystallin to protect upsilon-crystallin from oxidation and oxidative damage through radical-based oxidative stress mechanisms. Residues 22-41, 132-148, 212-227 and 245-264 of upsilon-crystallin display the greatest protection when interacted with alpha-crystallin at a ratio of 2 : 1 observed for the complex, which is commensurate with their levels measured in the eye of the platypus. Across each domain, a delay in the onset of oxidative damage is observed as the time of exposure to radicals is increased. The results are discussed in the context of the structure of the porcine homologue of upsilon-crystallin. Copyright 2006 John Wiley & Sons, Ltd.

Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo.

PubMed

Giacci, Marcus K; Bartlett, Carole A; Smith, Nicole M; Iyer, K Swaminathan; Toomey, Lillian M; Jiang, Haibo; Guagliardo, Paul; Kilburn, Matt R; Fitzgerald, Melinda

2018-06-18

Loss of function following injury to the central nervous system is worsened by secondary degeneration of neurons and glia surrounding the injury and initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semi-quantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury. 5-ethynyl-2'-deoxyuridine (EdU) was used to label cells that proliferated in the first 3 days after injury. Injury led to increases in DNA, protein and lipid damage in OPCs and mature oligodendrocytes at 3 days, regardless of proliferative state, associated with a decline in the numbers of OPCs at 7 days. O4+ pre-oligodendrocytes also exhibited increased lipid peroxidation. Interestingly, EdU+ mature oligodendrocytes derived after injury demonstrated increased early susceptibility to DNA damage and lipid peroxidation. However, EdU- mature oligodendrocytes with high 8OHdG immunoreactivity were more likely to be caspase3+. By day 28, newly derived mature oligodendrocytes had significantly reduced MYRF mRNA indicating that the myelination potential of these cells may be reduced. The proportion of caspase3+ oligodendrocytes remained higher in EdU- cells. Innovative use of NanoSIMS together with traditional immunohistochemistry and in situ hybridisation have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivo. SIGNIFICANCE STATEMENT Injury to the central nervous system is characterised by oxidative damage in areas adjacent to the injury. However, the cellular subpopulations and structures most vulnerable to this damage remain to be elucidated. Here we use powerful NanoSIMS techniques to show increased oxidative damage in oligodendroglia and axons and to demonstrate that cells early in the oligodendroglial lineage are the most vulnerable to DNA oxidation. Further immunohistochemical and in situ hybridisation investigation reveals that mature oligodendrocytes derived after injury are more vulnerable to oxidative damage than their counterparts existing at the time of injury and have reduced MYRF mRNA, yet pre-existing oligodendrocytes are more likely to die. Copyright © 2018 the authors.

Copper toxicity, oxidative stress, and antioxidant nutrients.

PubMed

Gaetke, Lisa M; Chow, Ching Kuang

2003-07-15

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Although normally bound to proteins, Cu may be released and become free to catalyze the formation of highly reactive hydroxyl radicals. Data obtained from in vitro and cell culture studies are largely supportive of Cu's capacity to initiate oxidative damage and interfere with important cellular events. Oxidative damage has been linked to chronic Cu-overload and/or exposure to excess Cu caused by accidents, occupational hazards, and environmental contamination. Additionally, Cu-induced oxidative damage has been implicated in disorders associated with abnormal Cu metabolism and neurodegenerative changes. Interestingly, a deficiency in dietary Cu also increases cellular susceptibility to oxidative damage. A number of nutrients have been shown to interact with Cu and alter its cellular effects. Vitamin E is generally protective against Cu-induced oxidative damage. While most in vitro or cell culture studies show that ascorbic acid aggravates Cu-induced oxidative damage, results obtained from available animal studies suggest that the compound is protective. High intakes of ascorbic acid and zinc may provide protection against Cu toxicity by preventing excess Cu uptake. Zinc also removes Cu from its binding site, where it may cause free radical formation. Beta-carotene, alpha-lipoic acid and polyphenols have also been shown to attenuate Cu-induced oxidative damage. Further studies are needed to better understand the cellular effects of this essential, but potentially toxic, trace mineral and its functional interaction with other nutrients.

DNA damage and glutathione level in children with asthma bronchiale: effect of antiasthmatic therapy.

PubMed

Hasbal, Canan; Aksu, Bagdagul Y; Himmetoglu, Solen; Dincer, Yildiz; Koc, Eylem E; Hatipoglu, Sami; Akcay, Tulay

2010-06-01

When the production of reactive oxygen species (ROS) exceeds the capacity of antioxidant defences, a condition known as oxidative stress occurs and it has been implicated in many pathological conditions including asthma. Interaction of ROS with DNA may result in mutagenic oxidative base modifications such as 8-hydroxydeoxyguanosine (8-oxo-dGuo) and DNA strand breaks. Reduced glutathione (GSH) serves as a powerful antioxidant against harmful effects of ROS. The aim of this study was to describe DNA damage as level of DNA strand breaks and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites, which reflects oxidative DNA damage and GSH level in children with mild-to-moderate persistent asthma; and to examine the effect of antiasthmatic therapy on these DNA damage parameters and GSH level. Before and after 8 wk of antiasthmatic therapy blood samples were taken, DNA strand breaks and Fpg-sensitive sites in peripheral leukocytes were determined by comet assay, GSH level of whole blood was measured by spectrophotometric method. DNA strand breaks and Fpg-sensitive sites in the asthma group were found to be increased as compared with control group. GSH level in the asthma group was not significantly different from those in the control group. Levels of strand breaks, Fpg-sensitive sites and GSH were found to be decreased in the asthma group after the treatment. In conclusion, oxidative DNA damage (strand breaks and Fpg-sensitive sites) is at a high level in children with asthma. DNA damage parameters and GSH level were found to be decreased after therapy. Our findings imply that antiasthmatic therapy including glucocorticosteroids not only controls asthma but also decreases mutation risk in children with asthma bronchiale.

Differential toxicity of arsenic on renal oxidative damage and urinary metabolic profiles in normal and diabetic mice.

PubMed

Yin, Jinbao; Liu, Su; Yu, Jing; Wu, Bing

2017-07-01

Diabetes is a common metabolic disease, which might influence susceptibility of the kidney to arsenic toxicity. However, relative report is limited. In this study, we compared the influence of inorganic arsenic (iAs) on renal oxidative damage and urinary metabolic profiles of normal and diabetic mice. Results showed that iAs exposure increased renal lipid peroxidation in diabetic mice and oxidative DNA damage in normal mice, meaning different effects of iAs exposure on normal and diabetic individuals. Nuclear magnetic resonance (NMR)-based metabolome analyses found that diabetes significantly changed urinary metabolic profiles of mice. Oxidative stress-related metabolites, such as arginine, glutamine, methionine, and β-hydroxybutyrate, were found to be changed in diabetic mice. The iAs exposure altered amino acid metabolism, lipid metabolism, carbohydrate metabolism, and energy metabolism in normal and diabetic mice, but had higher influence on metabolic profiles of diabetic mice than normal mice, especially for oxidative stress-related metabolites and metabolisms. Above results indicate that diabetes increased susceptibility to iAs exposure. This study provides basic information on differential toxicity of iAs on renal toxicity and urinary metabolic profiles in normal and diabetic mice and suggests that diabetic individuals should be considered as susceptible population in toxicity assessment of arsenic.

Eccentric localization of catalase to protect chromosomes from oxidative damages during meiotic maturation in mouse oocytes.

PubMed

Park, Yong Seok; You, Seung Yeop; Cho, Sungrae; Jeon, Hyuk-Joon; Lee, Sukchan; Cho, Dong-Hyung; Kim, Jae-Sung; Oh, Jeong Su

2016-09-01

The maintenance of genomic integrity and stability is essential for the survival of every organism. Unfortunately, DNA is vulnerable to attack by a variety of damaging agents. Oxidative stress is a major cause of DNA damage because reactive oxygen species (ROS) are produced as by-products of normal cellular metabolism. Cells have developed eloquent antioxidant defense systems to protect themselves from oxidative damage along with aerobic metabolism. Here, we show that catalase (CAT) is present in mouse oocytes to protect the genome from oxidative damage during meiotic maturation. CAT was expressed in the nucleus to form unique vesicular structures. However, after nuclear envelope breakdown, CAT was redistributed in the cytoplasm with particular focus at the chromosomes. Inhibition of CAT activity increased endogenous ROS levels, but did not perturb meiotic maturation. In addition, CAT inhibition produced chromosomal defects, including chromosome misalignment and DNA damage. Therefore, our data suggest that CAT is required not only to scavenge ROS, but also to protect DNA from oxidative damage during meiotic maturation in mouse oocytes.

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

PubMed

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

2001-11-01

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

Protective Effects of Gelam Honey against Oxidative Damage in Young and Aged Rats

PubMed Central

Sahhugi, Zulaikha; Jubri, Zakiah

2014-01-01

Aging is characterized by progressive decline in physiological and body function due to increase in oxidative damage. Gelam honey has been accounted to have high phenolic and nonphenolic content to attenuate oxidative damage. This study was to determine the effect of local gelam honey on oxidative damage of aged rats. Twenty-four male Spraque-Dawley rats were divided into young (2 months) and aged (19 months) groups. Each group was further divided into control (fed with plain water) and supplemented with 2.5 mg/kg body weight of gelam honey for 8 months. DNA damage level was determined by comet assay and plasma malondialdehyde (MDA) by high performance liquid chromatography (HPLC). The activity of blood and cardiac antioxidant enzymes was determined by spectrophotometer. The DNA damage and MDA level were reduced in both gelam honey supplemented groups. Gelam honey increases erythrocytes CAT and cardiac SOD activities in young and cardiac CAT activity in young and aged groups. The DNA damage was increased in the aged group compared to young group, but reduced at the end of the study. The decline of oxidative damage in rats supplemented with gelam honey might be through the modulation of antioxidant enzyme activities. PMID:25505937

Good Stress, Bad Stress and Oxidative Stress: Insights from Anticipatory Cortisol Reactivity

PubMed Central

Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M.; Dhabhar, Firdaus S.; Su, Yali; Epel, Elissa

2014-01-01

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F2α (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-OxoG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as “peak” cortisol reactivity, while the increase from 0 to 15 min was defined as “anticipatory” cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-OxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01.) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the Hypothalamic-Pituitary-Adrenal axis. It also supports the less studied model of ‘eustress’ - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage. PMID:23490070

Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity.

PubMed

Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M; Dhabhar, Firdaus S; Su, Yali; Epel, Elissa

2013-09-01

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less studied model of 'eustress' - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of complex polyphenols and tannins from red wine (WCPT) on chemically induced oxidative DNA damage in the rat.

PubMed

Casalini, C; Lodovici, M; Briani, C; Paganelli, G; Remy, S; Cheynier, V; Dolara, P

1999-08-01

Flavonoids are polyphenolic antioxidants occurring in vegetables and fruits as well as beverages such as tea and wine which have been thought to influence oxidative damage. We wanted to verify whether a complex mixture of wine tannins (wine complex polyphenols and tannins, WCPT) prevent chemically-induced oxidative DNA damage in vivo. Oxidative DNA damage was evaluated by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (80HdG)/ 2-deoxyguanosine (2dG) x 10(-6) in hydrolyzed DNA using HPLC coupled with electrochemical and UV detectors. We treated rats with WCPT (57 mg/kg p.o.) for 14 d, a dose 10-fold higher than what a moderate wine drinker would be exposed to. WCPT administration significantly reduced the ratio of 80HdG/2dG x 10(-6) in liver DNA obtained from rats treated with 2-nitropropane (2NP) relative to controls administered 2NP only (33. 3 +/- 2.5 vs. 44.9 +/- 3.2 x 10(-6) 2dG; micro +/- SE; p<0.05). On the contrary, pretreatment with WCPT for 10 d did not protect the colon mucosa from oxidative DNA damage induced by 1, 2-dimethylhydrazine (DMH). 2NP and DMH are hepatic and colon carcinogens, respectively, capable of inducing oxidative DNA damage. WCPT have protective action against some types of chemically-induced oxidative DNA damage in vivo.

On the Influence of Nb/Ti Ratio on Environmentally-Assisted Crack Growth in High-Strength Nickel-Based Superalloys

NASA Astrophysics Data System (ADS)

Németh, A. A. N.; Crudden, D. J.; Collins, D. M.; Kuksenko, V.; Liebscher, C. H.; Armstrong, D. E. J.; Wilkinson, A. J.; Reed, R. C.

2018-05-01

The effect of Nb/Ti ratio on environmentally-assisted crack growth of three prototype Ni-based superalloys is studied. For these alloys, the yield strength is unaltered with increasing Nb/Ti ratio due to an increase in grain size. This situation has allowed the rationalization of the factors influencing damage tolerance at 700 °C. Primary intergranular cracks have been investigated using energy-dispersive X-ray spectroscopy in a scanning transmission electron microscope and the analysis of electron back-scatter diffraction patterns. Any possible detrimental effect of Nb on the observed crack tip damage due to Nb-rich oxide formation is not observed. Instead, evidence is presented to indicate that the tertiary γ'-precipitates are dissolving ahead of the crack consistent with the formation of oxides such as alumina and rutile. Our results have implications for alloy design efforts; at any given strength level, both more and less damage-tolerant variants of these alloys can be designed.

Mechanisms of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced DNA damage in skin epidermal cells and fibroblasts.

PubMed

Inturi, Swetha; Tewari-Singh, Neera; Gu, Mallikarjuna; Shrotriya, Sangeeta; Gomez, Joe; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

2011-12-15

Employing mouse skin epidermal JB6 cells and dermal fibroblasts, here we examined the mechanisms of DNA damage by 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of sulfur mustard (SM). CEES exposure caused H2A.X and p53 phosphorylation as well as p53 accumulation in both cell types, starting at 1h, that was sustained for 24h, indicating a DNA-damaging effect of CEES, which was also confirmed and quantified by alkaline comet assay. CEES exposure also induced oxidative stress and oxidative DNA damage in both cell types, measured by an increase in mitochondrial and cellular reactive oxygen species and 8-hydroxydeoxyguanosine levels, respectively. In the studies distinguishing between oxidative and direct DNA damage, 1h pretreatment with glutathione (GSH) or the antioxidant Trolox showed a decrease in CEES-induced oxidative stress and oxidative DNA damage. However, only GSH pretreatment decreased CEES-induced total DNA damage measured by comet assay, H2A.X and p53 phosphorylation, and total p53 levels. This was possibly due to the formation of GSH-CEES conjugates detected by LC-MS analysis. Together, our results show that CEES causes both direct and oxidative DNA damage, suggesting that to rescue SM-caused skin injuries, pleiotropic agents (or cocktails) are needed that could target multiple pathways of mustard skin toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.

An association of cocoa consumption with improved physical fitness and decreased muscle damage and oxidative stress in athletes.

PubMed

González-Garrido, José A; García-Sánchez, José R; Garrido-Llanos, Silvia; Olivares-Corichi, Ivonne M

2017-04-01

Several studies have demonstrated the protective effects of cocoa consumption, due to its anti-inflammatory and antioxidant properties. Acute exercise induces oxidative stress and causes muscular damage during training. This study was designed to examine the effect of cocoa consumption on the markers of muscle damage, oxidative stress and physical fitness in professional soccer players. Fifteen players (15-18 years old) were included in the study. Biochemical parameters, markers of muscle damage and oxidative stress, and physical performance were evaluated before and after cocoa consumption. Biochemical parameters determined the healthy metabolic status of the study group; biomarkers of muscle and oxidative damage were measured in blood to establish muscle and redox status. However, high levels of biomarkers of muscle damage were detected. Interestingly, cocoa consumption decreased the muscle damage biomarkers of CK and LDH by 39.4% and 23.03%, respectively. The redox status was modified by a decrease in oxidative damage (carbonyl groups, 26.31%; thiol groups, 27.52%; MDA, 32.42%) and an increase in total antioxidant capacity (15.98%) and GSH-Px activity (26.37%). In addition, we observed an increase in physical performance by 4% in the Cooper Test. Our findings suggest that a short period of cocoa consumption could be useful in maintaining a good physical fitness, due to the favourable effects on muscle and redox status in athletes during exhaustive exercise.

Effect of curing agents on the oxidative and nitrosative damage to meat proteins during processing of fermented sausages.

PubMed

Villaverde, A; Morcuende, D; Estévez, M

2014-07-01

The effect of increasing concentrations of curing agents, ascorbate (0, 250, and 500 ppm), and nitrite (0, 75, and 150 ppm), on the oxidative and nitrosative damage to proteins during processing of fermented sausages was studied. The potential influence of these reactions on color and texture of the fermented sausages was also addressed. Nitrite had a pro-oxidant effect on tryptophan depletion and promoted the formation of protein carbonyls and Schiff bases. The nitration degree in the fermented sausages was also dependent on nitrite concentration. On the other hand, ascorbate acted as an efficient inhibitor of the oxidative and nitrosative damage to meat proteins. As expected, nitrite clearly favored the formation of the cured red color and ascorbate acted as an enhancer of color formation. Nitrite content was positively correlated with hardness. The chemistry behind the action of nitrite and ascorbate on muscle proteins during meat fermentation is thoroughly discussed. The results suggest that ascorbate (500 ppm) may be required to compensate the pro-oxidant impact of nitrite on meat proteins. This study provides insight on the action of curing agents on meat proteins during processing of fermented sausages. This chemistry background provides understanding of the potential influence of the oxidative and nitrosative damage to proteins on the quality of processed muscle foods. The study provides novel information on the impact of the combination of nitrite and ascorbate on the chemical deterioration of proteins and the influence on particular quality traits of fermented sausages. These data may be of interest for the design of cured muscle foods of enhanced quality. © 2014 Institute of Food Technologists®

Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

PubMed

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

Low-Damage Sputter Deposition on Graphene

NASA Astrophysics Data System (ADS)

Chen, Ching-Tzu; Casu, Emanuele; Gajek, Marcin; Raoux, Simone

2013-03-01

Despite its versatility and prevalence in the microelectronics industry, sputter deposition has seen very limited applications for graphene-based electronics. We have systematically investigated the sputtering induced graphene defects and identified the reflected high-energy neutrals of the sputtering gas as the primary cause of damage. In this talk, we introduce a novel sputtering technique that is shown to dramatically reduce bombardment of the fast neutrals and improve the structural integrity of the underlying graphene layer. We also demonstrate that sputter deposition and in-situ oxidation of 1 nm Al film at elevated temperatures yields homogeneous, fully covered oxide films with r.m.s. roughness much less than 1 monolayer, which shows the potential of using such technique for gate oxides, tunnel barriers, and multilayer fabrication in a wide range of graphene devices.

Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption.

PubMed

Kita, Taizo; Wagner, George C; Nakashima, Toshikatsu

2003-07-01

Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson's disease.

Spirulina improves antioxidant status by reducing oxidative stress in rabbits fed a high-cholesterol diet.

PubMed

Kim, Mi Yeon; Cheong, Sun Hee; Lee, Jeung Hee; Kim, Min Ji; Sok, Dai-Eun; Kim, Mee Ree

2010-04-01

The beneficial effect of Spirulina (Spirulina platensis) on tissue lipid peroxidation and oxidative DNA damage was tested in the hypercholesterolemic New Zealand White rabbit model. After hypercholesterolemia was induced by feeding a high cholesterol (0.5%) diet (HCD) for 4 weeks, then HCD supplemented with 1% or 5% Spirulina (SP1 or SP5, respectively) was provided for an additional 8 weeks. Spirulina supplementation significantly reduced the increased lipid peroxidation level in HCD-fed rabbits, and levels recovered to control values. Oxidative stress biomarkers such as glutathione, glutathione peroxidase, glutathione reductase, and glutathione S-transferase were significantly improved in the liver and red blood cells of rabbits fed SP1. Furthermore, SP5 induced antioxidant enzyme activity by 3.1-fold for glutathione, 2.5-fold for glutathione peroxidase, 2.7-fold for glutathione reductase, and 2.3-fold for glutathione S-transferase in liver, compared to the HCD group. DNA damage in lymphocytes was significantly reduced in both the SP1 and SP5 groups, based on the comet assay. Findings from the present study suggest that dietary supplementation with Spirulina may be useful to protect the cells from lipid peroxidation and oxidative DNA damage.

NEIL3 Repairs Telomere Damage during S Phase to Secure Chromosome Segregation at Mitosis.

PubMed

Zhou, Jia; Chan, Jany; Lambelé, Marie; Yusufzai, Timur; Stumpff, Jason; Opresko, Patricia L; Thali, Markus; Wallace, Susan S

2017-08-29

Oxidative damage to telomere DNA compromises telomere integrity. We recently reported that the DNA glycosylase NEIL3 preferentially repairs oxidative lesions in telomere sequences in vitro. Here, we show that loss of NEIL3 causes anaphase DNA bridging because of telomere dysfunction. NEIL3 expression increases during S phase and reaches maximal levels in late S/G2. NEIL3 co-localizes with TRF2 and associates with telomeres during S phase, and this association increases upon oxidative stress. Mechanistic studies reveal that NEIL3 binds to single-stranded DNA via its intrinsically disordered C terminus in a telomere-sequence-independent manner. Moreover, NEIL3 is recruited to telomeres through its interaction with TRF1, and this interaction enhances the enzymatic activity of purified NEIL3. Finally, we show that NEIL3 interacts with AP Endonuclease 1 (APE1) and the long-patch base excision repair proteins PCNA and FEN1. Taken together, we propose that NEIL3 protects genome stability through targeted repair of oxidative damage in telomeres during S/G2 phase. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A Topical Mitochondria-Targeted Redox Cycling Nitroxide Mitigates Oxidative Stress Induced Skin Damage

PubMed Central

Brand, Rhonda M.; Epperly, Michael W.; Stottlemyer, J. Mark; Skoda, Erin M.; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E.; Greenberger, Joel S.; Falo, Louis D.

2017-01-01

Skin is the largest human organ and provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation induced skin damage ranges from photoaging and cutaneous carcinogenesis from UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species (ROS). Mitochondria are particularly susceptible to oxidative stress, and mitochondrial dependent apoptosis plays a major role in radiation induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent ROS accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrial targeted antioxidant prevents and mitigates radiation induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin’s antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. PMID:27794421

Evaluation of oxidative DNA damage promoted by storage in sperm from sex-reversed rainbow trout.

PubMed

Pérez-Cerezales, S; Martínez-Páramo, S; Cabrita, E; Martínez-Pastor, F; de Paz, P; Herráez, M P

2009-03-01

Short-term storage and cryopreservation of sperm are two common procedures in aquaculture, used for routine practices in artificial insemination reproduction and gene banking, respectively. Nevertheless, both procedures cause injuries affecting sperm motility, viability, cell structure and DNA stability, which diminish reproductive success. DNA modification is considered extremely important, especially when sperm storage is carried out with gene banking purposes. DNA damage caused by sperm storage is not well characterized and previous studies have reported simple and double strand breaks that have been attributed to oxidative events promoted by the generation of free radicals during storage. The objective of this study was to reveal DNA fragmentation and to explore the presence of oxidized bases that could be produced by oxidative events during short-term storage and cryopreservation in sex-reversed rainbow trout (Oncorhynchus mykiss) spermatozoa. Sperm from six males was analyzed separately. Different aliquots of the samples were stored 2h (fresh) or 5 days at 4 degrees C or were cryopreserved. Then spermatozoa were analyzed using the Comet assay, as well as combining this method with digestion with two endonucleases from Escherichia coli (Endonuclease III, that cut in oxidized cytosines, and FPG, cutting in oxidized guanosines). Both storage procedures yielded DNA fragmentation, but only short-term storage oxidative events were clearly detected, showing that oxidative processes affect guanosines rather than cytosines. Cryopreservation increases DNA fragmentation but the presence of oxidized bases was not noticed, suggesting that mechanisms other than oxidative stress could be involved in DNA fragmentation promoted by freezing.

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

PubMed

Vaseghi, H; Houshmand, M; Jadali, Z

2017-10-01

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

Oxidized Base Damage and Single-Strand Break Repair in Mammalian Genomes: Role of Disordered Regions and Posttranslational Modifications in Early Enzymes

PubMed Central

Hegde, Muralidhar L.; Izumi, Tadahide; Mitra, Sankar

2012-01-01

Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/ SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed. PMID:22749145

Oxidative damage and antioxidant defense in thymus of malnourished lactating rats.

PubMed

Gavia-García, Graciela; González-Martínez, Haydeé; Miliar-García, Ángel; Bonilla-González, Edmundo; Rosas-Trejo, María de Los Ángeles; Königsberg, Mina; Nájera-Medina, Oralia; Luna-López, Armando; González-Torres, María Cristina

2015-01-01

Malnutrition has been associated with oxidative damage by altered antioxidant protection mechanisms. Specifically, the aim of this study was to evaluate oxidative damage (DNA and lipid) and antioxidant status (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT] mRNA, and protein expression) in thymus from malnourished rat pups. Malnutrition was induced during the lactation period by the food competition method. Oxidative DNA damage was determined quantifying 8-oxo-7, 8-dihydro-2'-deoxyguanosine adduct by high-performance liquid chromatography. Lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances. Levels of gene and protein expression of SOD, GPx, and CAT were evaluated by real-time polymerase chain reaction and Western blot, respectively. Antioxidant enzyme activities were measured spectrophotometrically. Oxidative DNA damage and lipid peroxidation significantly increased in second-degree (MN-2) and third-degree malnourished (MN-3) rats compared with well-nourished rats. Higher amounts of oxidative damage, lower mRNA expression, and lower relative concentrations of protein, as well as decreased antioxidant activity of SOD, GPx, and CAT were associated with the MN-2 and MN-3 groups. The results of this study demonstrated that higher body-weight deficits were related to alterations in antioxidant protection, which contribute to increased levels of damage in the thymus. To our knowledge, this study demonstrated for the first time that early in life, malnutrition leads to increased DNA and lipid oxidative damage, attributable to damaged antioxidant mechanisms including transcriptional and enzymatic activity alterations. These findings may contribute to the elucidation of the causes of previously reported thymus dysfunction, and might explain partially why children and adults who have overcome child undernourishment experience immunologic deficiencies. Copyright © 2015 Elsevier Inc. All rights reserved.

In situ evaluation of heavy metal-DNA interactions using an electrochemical DNA biosensor.

PubMed

Oliveira, S C B; Corduneanu, O; Oliveira-Brett, A M

2008-02-01

Heavy metal ions, lead, cadmium and nickel, are well known carcinogens with natural different origins and their direct mode of action is still not fully understood. A dsDNA-electrochemical biosensor, employing differential pulse voltammetry, was used for the in situ evaluation of Pb2+, Cd2+ and Ni2+ interaction with dsDNA. The results confirm that Pb2+, Cd2+ and Ni2+ bind to dsDNA, and that this interaction leads to different modifications in the dsDNA structure. These modifications were electrochemically recognized as changes in the oxidation peaks of guanosine and adenosine bases. Using homopolynucleotides of guanine and adenine it has been proved that the interaction between Pb2+ and DNA causes oxidative damage and preferentially takes place at adenine-containing segments, with the formation of 2,8-dihydroxyadenine, the oxidation product of adenine residues and a biomarker of DNA oxidative damage. The Pb2+ bound to dsDNA can still undergo oxidation. The interaction of Cd2+ and Ni2+ causes conformational changes, destabilizing the double helix, which can enable the action of other oxidative agents on DNA.

Rhesus monkey lens as an in vitro model for studying oxidative stress

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

Zigler, J.S. Jr.; Lucas, V.A.; Du, X.Y.

1989-10-01

Lenses from young rhesus monkeys were incubated in the presence of H{sub 2}O{sub 2} or oxygen radical generating systems to determine their suitability as a model for investigating lenticular oxidative stress. Additionally, direct comparisons were made between the effects found with the monkey lenses and those observed with cultured rat lenses exposed to the same oxidizing systems. As in earlier studies with rat lenses the monkey lenses exhibited impaired ability to actively accumulate from the medium radioactively labelled rubidium and choline following exposure to oxidative stress. Based on the effects of various scavengers of oxygen radicals it appeared that themore » mechanisms responsible for lens damage were the same for both rat and monkey lenses. However, rat lenses were damaged by lower concentrations of oxidants than were monkey lenses. It was concluded that oxidative stress affects both rat and monkey lenses by similar mechanisms but that lenses from monkeys, and probably other primates, are more resistant to these effects because they have better endogenous antioxidant defenses.« less

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF-κB/p65 Activation

PubMed Central

Jiang, Wenkai; Zhou, Lin

2016-01-01

Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2) to induce the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies. PMID:27818721

Comparative analysis of the relative potential of silver, Zinc-oxide and titanium-dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin carcinogenesis.

PubMed

Tyagi, Nikhil; Srivastava, Sanjeev K; Arora, Sumit; Omar, Yousef; Ijaz, Zohaib Mohammad; Al-Ghadhban, Ahmed; Deshmukh, Sachin K; Carter, James E; Singh, Ajay P; Singh, Seema

2016-12-01

Sunscreen formulations containing UVB filters, such as Zinc-oxide (ZnO) and titanium-dioxide (TiO 2 ) nanoparticles (NPs) have been developed to limit the exposure of human skin to UV-radiations. Unfortunately, these UVB protective agents have failed in controlling the skin cancer incidence. We recently demonstrated that silver nanoparticles (Ag-NPs) could serve as novel protective agents against UVB-radiations. Here our goal was to perform comparative analysis of direct and indirect UVB-protection efficacy of ZnO-, TiO 2 - and Ag-NPs. Sun-protection-factor calculated based on their UVB-reflective/absorption abilities was the highest for TiO 2 -NPs followed by Ag- and ZnO-NPs. This was further confirmed by studying indirect protection of UVB radiation-induced death of HaCaT cells. However, only Ag-NPs were active in protecting HaCaT cells against direct UVB-induced DNA-damage by repairing bulky-DNA lesions through nucleotide-excision-repair mechanism. Moreover, Ag-NPs were also effective in protecting HaCaT cells from UVB-induced oxidative DNA damage by enhancing SOD/CAT/GPx activity. In contrast, ZnO- and TiO 2 -NPs not only failed in providing any direct protection from DNA-damage, but rather enhanced oxidative DNA-damage by increasing ROS production. Together, these findings raise concerns about safety of ZnO- and TiO 2 -NPs and establish superior protective efficacy of Ag-NPs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

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

Dong, Hui; Shi, Qiong; Song, Xiufang

2015-07-01

Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observedmore » phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.« less

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

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

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

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

Oxidative Stress Resistance in Deinococcus radiodurans†

PubMed Central

Slade, Dea; Radman, Miroslav

2011-01-01

Summary: Deinococcus radiodurans is a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience of D. radiodurans to oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems. D. radiodurans assets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such as D. radiodurans have substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook on D. radiodurans strategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection in D. radiodurans is therefore of considerable potential interest for medicine and public health. PMID:21372322

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

PubMed Central

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

PubMed

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-10-01

The free radical, or oxidative stress, theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging because of the existence of species with tremendously different natural life spans, including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity, and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus, and Strongylocentrotus purpuratus, which has an intermediate life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age pigment lipofuscin, measured in muscle, nerve, and esophagus, increased with age; however, it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species; however, further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age, and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. Copyright © 2013 Elsevier Inc. All rights reserved.

SIRT3 Links Oxidative Stress with Aging and Cancer | Center for Cancer Research

Cancer.gov

When cells produce energy, they also form reactive oxygen molecules capable of damaging proteins and DNA. Normally, these molecules are neutralized by a protein called superoxide dismutase, or SOD. However, as a cell ages, oxidative damage accumulates. The increase in oxidative cellular damage as people age may provide a mechanistic connection between aging and carcinogenesis.

Radioprotective effects of honeybee venom (Apis mellifera) against 915-MHz microwave radiation-induced DNA damage in wistar rat lymphocytes: in vitro study.

PubMed

Gajski, Goran; Garaj-Vrhovac, Vera

2009-01-01

The aim of this study is to investigate the radioprotective effect of bee venom against DNA damage induced by 915-MHz microwave radiation (specific absorption rate of 0.6 W/kg) in Wistar rats. Whole blood lymphocytes of Wistar rats are treated with 1 microg/mL bee venom 4 hours prior to and immediately before irradiation. Standard and formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assays are used to assess basal and oxidative DNA damage produced by reactive oxygen species. Bee venom shows a decrease in DNA damage compared with irradiated samples. Parameters of Fpg-modified comet assay are statistically different from controls, making this assay more sensitive and suggesting that oxidative stress is a possible mechanism of DNA damage induction. Bee venom is demonstrated to have a radioprotective effect against basal and oxidative DNA damage. Furthermore, bee venom is not genotoxic and does not produce oxidative damage in the low concentrations used in this study.

The Fpg/Nei family of DNA glycosylases: substrates, structures, and search for damage.

PubMed

Prakash, Aishwarya; Doublié, Sylvie; Wallace, Susan S

2012-01-01

During the initial stages of the base excision DNA repair pathway, DNA glycosylases are responsible for locating and removing the majority of endogenous oxidative base lesions. The bifunctional formamidopyrimidine DNA glycosylase (Fpg) and endonuclease VIII (Nei) are members of the Fpg/Nei family, one of the two families of glycosylases that recognize oxidized DNA bases, the other being the HhH/GPD (or Nth) superfamily. Structural and biochemical developments over the past decades have led to novel insights into the mechanism of damage recognition by the Fpg/Nei family of enzymes. Despite the overall structural similarity among members of this family, these enzymes exhibit distinct features that make them unique. This review summarizes the current structural knowledge of the Fpg/Nei family members, emphasizes their substrate specificities, and describes how these enzymes search for lesions. Copyright © 2012 Elsevier Inc. All rights reserved.

Oxidation in the nucleotide pool, the DNA damage response and cellular senescence: Defective bricks build a defective house.

PubMed

Rai, Priyamvada

2010-11-28

Activation of persistent DNA damage response (DDR) signaling is associated with the induction of a permanent proliferative arrest known as cellular senescence, a phenomenon intrinsically linked to both tissue aging as well as tumor suppression. The DNA damage observed in senescent cells has been attributed to elevated levels of reactive oxygen species (ROS), failing DNA damage repair processes, and/or oncogenic activation. It is not clear how labile molecules such as ROS are able to damage chromatin-bound DNA to a sufficient extent to invoke persistent DNA damage and DDR signaling. Recent evidence suggests that the nucleotide pool is a significant target for oxidants and that oxidized nucleotides, once incorporated into genomic DNA, can lead to the induction of a DNA strand break-associated DDR that triggers senescence in normal cells and in cells sustaining oncogene activation. Evasion of this DDR and resulting senescence is a key step in tumor progression. This review will explore the role of oxidation in the nucleotide pool as a major effector of oxidative stress-induced genotoxic damage and DDR in the context of cellular senescence and tumorigenic transformation. 2010 Elsevier B.V. All rights reserved.

A Role for the Fifth G-Track in G-Quadruplex Forming Oncogene Promoter Sequences during Oxidative Stress: Do These “Spare Tires” Have an Evolved Function?

PubMed Central

2015-01-01

Uncontrolled inflammation or oxidative stress generates electron-deficient species that oxidize the genome increasing its instability in cancer. The G-quadruplex (G4) sequences regulating the c-MYC, KRAS, VEGF, BCL-2, HIF-1α, and RET oncogenes, as examples, are targets for oxidation at loop and 5′-core guanines (G) as showcased in this study by CO3•– oxidation of the VEGF G4. Products observed include 8-oxo-7,8-dihydroguanine (OG), spiroiminodihydantoin (Sp), and 5-guanidinohydantoin (Gh). Our previous studies found that OG and Gh, when present in the four G-tracks of the solved structure for VEGF and c-MYC, were not substrates for the base excision repair (BER) DNA glycosylases in biologically relevant KCl solutions. We now hypothesize that a fifth G-track found a few nucleotides distant from the G4 tracks involved in folding can act as a “spare tire,” facilitating extrusion of a damaged G-run into a large loop that then becomes a substrate for BER. Thermodynamic, spectroscopic, and DMS footprinting studies verified the fifth domain replacing a damaged G-track with OG or Gh at a loop or core position in the VEGF G4. These new “spare tire”-containing strands with Gh in loops are now found to be substrates for initiation of BER with the NEIL1, NEIL2, and NEIL3 DNA glycosylases. The results support a hypothesis in which regulatory G4s carry a “spare-tire” fifth G-track for aiding in the repair process when these sequences are damaged by radical oxygen species, a feature observed in a large number of these sequences. Furthermore, formation and repair of oxidized bases in promoter regions may constitute an additional example of epigenetic modification, in this case of guanine bases, to regulate gene expression in which the G4 sequences act as sensors of oxidative stress. PMID:26405692

Combined Advanced Finishing and UV-Laser Conditioning for Producing UV-Damage-Resistant Fused Silica Optics

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

Menapace, J A; Penetrante, B; Golini, D

2001-11-01

Laser induced damage initiation on fused silica optics can limit the lifetime of the components when used in high power UV laser environments. Foe example in inertial confinement fusion research applications, the optics can be exposed to temporal laser pulses of about 3-nsec with average fluences of 8 J/cm{sup 2} and peak fluences between 12 and 15 J/cm{sup 2}. During the past year, we have focused on optimizing the damage performance at a wavelength of 355-nm (3{omega}), 3-nsec pulse length, for optics in this category by examining a variety of finishing technologies with a challenge to improve the laser damagemore » initiation density by at least two orders of magnitude. In this paper, we describe recent advances in improving the 3{omega} damage initiation performance of laboratory-scale zirconium oxide and cerium oxide conventionally finished fused silica optics via application of processes incorporating magnetorheological finishing (MRF), wet chemical etching, and UV laser conditioning. Details of the advanced finishing procedures are described and comparisons are made between the procedures based upon large area 3{omega} damage performance, polishing layer contamination, and optical subsurface damage.« less

Drosophila TDP1 Ortholog Important for Longevity and Nervous System Maintenance | Center for Cancer Research

Cancer.gov

As the molecule responsible for encoding a cell’s hereditary information, DNA must maintain its integrity. However, nucleic acids are vulnerable to damage by a number of endogenous and exogenous insults, such as reactive oxygen species or enzymes that react with DNA. Thus, other enzymes are tasked with repairing damaged DNA, including tyrosyl-DNA phosphodiesterase 1 (TDP1), which frees the 3’ ends of DNA that are blocked by proteins and oxidized bases to allow the ligation of strand breaks. Yeast, mice, and humans that express mutants of TDP1 have a reduced capacity to repair oxidative or topoisomerase-induced damage. A Drosophila TDP1 ortholog, glaikit (gkt), has been reported, but its function in DNA repair has not been evaluated because, surprisingly, gkt knockout flies were not viable.

New Energy-Dependent Soft X-Rav Damage In MOS Devices

NASA Astrophysics Data System (ADS)

Chan, Tung-Yi; Gaw, Henry; Seligson, Daniel; Pan, Lawrence; King, Paul L.; Pianetta, Piero

1988-06-01

An energy-dependent soft x-ray-induced device damage has been discovered in MOS devices fabricated using standard CMOS process. MOS devices were irradiated by monochromatic x-rays in energy range just above and below the silicon K-edge (1.84 keV). Photons below the K-edge is found to create more damage in the oxide and oxide/silicon interface than photons above the K-edge. This energy-dependent damage effect is believed to be due to charge traps generated during device fabrication. It is found that data for both n- and p-type devices lie along a universal curve if normalized threshold voltage shifts are plotted against absorbed dose in the oxide. The threshold voltage shift saturates when the absorbed dose in the oxide exceeds 1.4X105 mJ/cm3, corresponding to 6 Mrad in the oxide. Using isochronal anneals, the trapped charge damage is found to recover with an activation energy of 0.38 eV. A discrete radiation-induced damage state appears in the low frequency C-V curve in a temperature range from 1750C to 325°C.

Quercitrin Protects Skin from UVB-induced Oxidative Damage

PubMed Central

Yin, Yuanqin; Li, Wenqi; Son, Yong-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-01-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. PMID:23545178

Quercitrin protects skin from UVB-induced oxidative damage.

PubMed

Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-06-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. Copyright © 2013 Elsevier Inc. All rights reserved.

ATM directs DNA damage responses and proteostasis via genetically separable pathways

PubMed Central

Lee, Ji-Hoon; Mand, Michael R.; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W.; Richards, Alicia L.; Coon, Joshua J.; Paull, Tanya T.

2018-01-01

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes Ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. Here, we genetically separated DNA damage activation of ATM from oxidative activation using separation-of-function mutations. We found that deficiency in ATM activation by Mre11-Rad50-Nbs1 and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of ATM lacking oxidative activation generates widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicates ATM in the control of protein homeostasis. PMID:29317520

The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters.

PubMed

Du, Wei; Rani, Reena; Sipple, Jared; Schick, Jonathan; Myers, Kasiani C; Mehta, Parinda; Andreassen, Paul R; Davies, Stella M; Pang, Qishen

2012-05-03

Oxidative stress has been implicated in the pathogenesis of many human diseases including Fanconi anemia (FA), a genetic disorder associated with BM failure and cancer. Here we show that major antioxidant defense genes are down-regulated in FA patients, and that gene down-regulation is selectively associated with increased oxidative DNA damage in the promoters of the antioxidant defense genes. Assessment of promoter activity and DNA damage repair kinetics shows that increased initial damage, rather than a reduced repair rate, contributes to the augmented oxidative DNA damage. Mechanistically, FA proteins act in concert with the chromatin-remodeling factor BRG1 to protect the promoters of antioxidant defense genes from oxidative damage. Specifically, BRG1 binds to the promoters of the antioxidant defense genes at steady state. On challenge with oxidative stress, FA proteins are recruited to promoter DNA, which correlates with significant increase in the binding of BRG1 within promoter regions. In addition, oxidative stress-induced FANCD2 ubiquitination is required for the formation of a FA-BRG1-promoter complex. Taken together, these data identify a role for the FA pathway in cellular antioxidant defense.

N-Acetylcysteine supplementation reduces oxidative stress and DNA damage in children with β-thalassemia.

PubMed

Ozdemir, Zeynep Canan; Koc, Ahmet; Aycicek, Ali; Kocyigit, Abdurrahim

2014-01-01

There are several reports that increased oxidative stress and DNA damage were found in β-thalassemia major (β-TM) patients. In this study, we aimed to evaluate the effects of N-acetylcysteine (NAC) and vitamin E on total oxidative stress and DNA damage in children with β-TM. Seventy-five children with transfusion-dependent β-thalassemia (β-thal) were randomly chosen to receive 10 mg/kg/day of NAC or 10 IU/kg/day of vitamin E or no supplementation; 28 healthy controls were also included in the study. Serum total oxidant status (TOS) and total antioxidant capacity (TAC) were measured, oxidative stress index (OSI) was calculated, and mononuclear DNA damage was assessed by alkaline comet assay; they were determined before treatment and after 3 months of treatment. Total oxydent status, OSI, and DNA damage levels were significantly higher and TAC levels were significantly lower in the thalassemic children than in the healthy controls (p < 0.001). In both supplemented groups, mean TOS and OSI levels were decreased; TAC and pre transfusion hemoglobin (Hb) levels were significantly increased after 3 months (p ≤ 0.002). In the NAC group, DNA damage score decreased (p = 0.001). N-Acetylcysteine and vitamin E may be effective in reducing serum oxidative stress and increase pre transfusion Hb levels in children with β-thal. N-Acetylcysteine also can reduce DNA damage.

Quercitrin protects skin from UVB-induced oxidative damage

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

Yin, Yuanqin; Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY; Li, Wenqi

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidativemore » damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.« less

Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest

PubMed Central

Hackenhaar, Fernanda S.; Medeiros, Tássia M.; Heemann, Fernanda M.; Behling, Camile S.; Putti, Jordana S.; Mahl, Camila D.; Verona, Cleber; da Silva, Ana Carolina A.; Guerra, Maria C.; Gonçalves, Carlos A. S.; Oliveira, Vanessa M.; Riveiro, Diego F. M.; Vieira, Silvia R. R.

2017-01-01

After cardiac arrest, organ damage consequent to ischemia-reperfusion has been attributed to oxidative stress. Mild therapeutic hypothermia has been applied to reduce this damage, and it may reduce oxidative damage as well. This study aimed to compare oxidative damage and antioxidant defenses in patients treated with controlled normothermia versus mild therapeutic hypothermia during postcardiac arrest syndrome. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 h mild therapeutic hypothermia (33°C), victims of in- or out-of-hospital cardiac arrest. Parameters were assessed at 6, 12, 36, and 72 h after cardiac arrest in the central venous blood samples. Hypothermic and normothermic patients had similar S100B levels, a biomarker of brain injury. Xanthine oxidase activity is similar between hypothermic and normothermic patients; however, it decreases posthypothermia treatment. Xanthine oxidase activity is positively correlated with lactate and S100B and inversely correlated with pH, calcium, and sodium levels. Hypothermia reduces malondialdehyde and protein carbonyl levels, markers of oxidative damage. Concomitantly, hypothermia increases the activity of erythrocyte antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase while decreasing the activity of serum paraoxonase-1. These findings suggest that mild therapeutic hypothermia reduces oxidative damage and alters antioxidant defenses in postcardiac arrest patients. PMID:28553435

Oxidative damage to macromolecules in human Parkinson’s disease and the rotenone model

PubMed Central

Sanders, Laurie H.; Greenamyre, J. Timothy

2013-01-01

Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is associated with selective degeneration of nigrostriatal dopamine neurons. While the underlying mechanisms contributing to neurodegeneration in PD appear to be multifactorial, mitochondrial impairment and oxidative stress are widely considered to be central to many forms of the disease. Whether oxidative stress is a cause or consequence of dopaminergic death, there is substantial evidence for oxidative stress in both human PD patients and in animal models of PD, especially using rotenone, a complex I inhibitor. There are many indices of oxidative stress, but this review covers the recent evidence for oxidative damage to nucleic acids, lipids and proteins in both the brain and peripheral tissues in human PD and in the rotenone model. Limitations of the existing literature and future perspectives are discussed. Understanding how each particular macromolecule is damaged by oxidative stress and the interplay of secondary damage to other biomolecules may help design better targets for treatment of PD. PMID:23328732

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

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

Laha, Dipranjan; Pramanik, Arindam; Laskar, Aparna

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Sphericalmore » shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain.« less

Black soybean seed coat polyphenols prevent AAPH-induced oxidative DNA-damage in HepG2 cells

PubMed Central

Yoshioka, Yasukiyo; Li, Xiu; Zhang, Tianshun; Mitani, Takakazu; Yasuda, Michiko; Nanba, Fumio; Toda, Toshiya; Yamashita, Yoko; Ashida, Hitoshi

2017-01-01

Black soybean seed coat extract (BE), which contains abundant polyphenols such as procyanidins, cyanidin 3-glucoside, (+)-catechin, and (−)­epicatechin, has been reported on health beneficial functions such as antioxidant activity, anti-inflammatory, anti-obesity, and anti-diabetic activities. In this study, we investigated that prevention of BE and its polyphenols on 2,2'-azobis(2-methylpropionamide) dihydrochloride (AAPH)-induced oxidative DNA damage, and found that these polyphenols inhibited AAPH-induced formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for oxidative DNA damage in HepG2 cells. Under the same conditions, these polyphenols also inhibited AAPH-induced accumulation of reactive oxygen species (ROS) in the cells. Inhibition of ROS accumulation was observed in both cytosol and nucleus. It was confirmed that these polyphenols inhibited formation of AAPH radical using oxygen radical absorbance capacity assay under the cell-free conditions. These results indicate that polyphenols in BE inhibit free radical-induced oxidative DNA damages by their potent antioxidant activity. Thus, BE is an effective food material for prevention of oxidative stress and oxidative DNA damages. PMID:28366989

Biomarkers of oxidative stress and cataract. Novel drug delivery therapeutic strategies targeting telomere reduction and the expression of telomerase activity in the lens epithelial cells with N-acetylcarnosine lubricant eye drops: anti-cataract which helps to prevent and treat cataracts in the eyes of dogs and other animals.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2014-01-01

Cataracts in small animals are shown to be at least partially caused by oxidative damage to lens epithelial cells (LECs) and the internal lens; biomarkers of oxidative stress in the lens are considered as general biomarkers for life expectancy in the canine and other animals. Telomeres lengths and expressed telomerase activity in canine LECs may serve as important monitors of oxidative damage in normal LECs with documented higher levels of telomerase activity in cataractous LECs during cells' lifespan. Loss of functional telomere length below a critical threshold in LECs of canines during the effect of UV and chronic oxidative stress or metabolic failure, can activate programs leading to LEC senescence or death. Telomerase is induced in LECs of canines at critical stages of cataractogenesis initiation and exposure to oxidative stress through the involvement of catalytically active prooxidant transition metal (iron) ions. This work documents that transition metal ions (such as, ferrous ions- catalytic oxidants) might induce premature senescence in LECs of canines, telomere shortening with increased telomerase activity as adaptive response to UV light, oxidative and metabolic stresses. The therapeutic treatment with 1% N-acetylcarnosine (NAC) prodrug delivery is beneficial for prevention and dissolution of ripe cataracts in canines. This biological activity is based on the findings of ferroxidase activity pertinent to the dipeptide carnosine released ophthalmically from NAC prodrug of L-carnosine, stabilizing properties of carnosine on biological membranes based on the ability of the imidazole-containing dipeptides to interact with lipid peroxidation products and reactive oxygen species (ROS), to prevent membrane damage and delute the associated with membrane fragements protein aggregates. The advent of therapeutic treatment of cataracts in canines with N-acetylcarnosine lubricant eye drops through targeting the prevention of loss of functional telomere length below a critical threshold and "flirting" with an indirect effect with telomerase expression in LECs of canines during the effects of UV, chronic oxidative stress increases the successful rate of cataract management challenges in home veterinary care.

The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.

PubMed

Lowes, Damon A; Thottakam, Bensita M V; Webster, Nigel R; Murphy, Michael P; Galley, Helen F

2008-12-01

Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondrial membrane potential was augmented (P<0.01) in most organs. These findings suggest that the use of mitochondria-targeted antioxidants such as MitoQ may be beneficial in sepsis.

Oxidative damage of DNA in subjects occupationally exposed to lead.

PubMed

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

2017-09-01

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

The effect of green, black and white tea on the level of alpha and gamma tocopherols in free radical-induced oxidative damage of human red blood cells.

PubMed

Gawlik, Małgorzata; Czajka, Aneta

2007-01-01

The present study was undertaken to investigate the effect of aqueous tea extracts on lipid peroxidation and alpha and gamma tocopherols concentration in the oxidative damage of human red blood cells (RBC). RBC was taken as the model for study of the oxidative damage was induced by cumene hydroperoxide (cumOOH). The antioxidative property of leaf green tea, leaf and granulate of black tea and white tea at levels 1, 2, 4 g/150 mL of water were evaluated. The correlation was observed between reducing power of tea extract and formation of malondialdehyde--MDA (an indicator of lipid peroxidation) in oxidative damage of RBC. All tea extracts at level of 4 g/150 mL of water significantly decreased concentration of MDA. The extract of green tea in comparison to black and white tea extracts at the same levels seems to be a better protective agent against oxidative stress. The antioxidant synergism between components extracted from leaves of green tea and endogenous alpha tocopherol in the oxidative damage of red blood cells was observed. The consumption of alpha tocopherol in oxidative damage of RBC was the lowest after treatment with the highest dose of green tea extract. All tea extracts did not protect against decrease of gamma tocopherol in human erythrocytes treated with cumOOH.

Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis.

PubMed

van 't Erve, Thomas J; Kadiiska, Maria B; London, Stephanie J; Mason, Ronald P

2017-08-01

The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures. In this meta-analysis, the F 2 -isoprostane, 8-iso-PGF 2α , was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges' g) in 8-iso-PGF 2α levels between affected and control populations were calculated. The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF 2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF 2α levels (g<0.8) were found in the following conditions: hypertension (g=0.4), metabolic syndrome (g=0.5), asthma (g=0.4), and tobacco smoking (g=0.7). In contrast, large increases in 8-iso-PGF 2α levels were observed in pathologies of the kidney, e.g., chronic renal insufficiency (g=1.9), obstructive sleep apnoea (g=1.1), and pre-eclampsia (g=1.1), as well as respiratory tract disorders, e.g., cystic fibrosis (g=2.3). In conclusion, we have established a quantitative classification for the level of 8-iso-PGF 2α generation in different human pathologies and exposures based on a comprehensive meta-analysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation. Copyright © 2017. Published by Elsevier B.V.

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

PubMed

Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

2016-07-19

Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis

PubMed Central

Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R.; Stuehr, Dennis J.

2016-01-01

Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage. PMID:27382160

[Oxidative stress and infectious pathology].

PubMed

Romero Alvira, D; Guerrero Navarro, L; Gotor Lázaro, M A; Roche Collado, E

1995-03-01

Pathogenic organism can be considered as pro-oxidant agents because they produce cell death and tissue damage. In addition organism can be eliminated by specific cell defense mechanism which utilize in part, reactive oxygen radicals formed by oxidative stress responses. The cause of the necessarily defense process results in cell damage thereby leading to development of inflammation, a characteristic oxidative stress situation. This fact shows the duality of oxidative stress in infections and inflammation: oxygen free radicals protect against microorganism attack and can produce tissue damage during this protection to trigger inflammation. Iron, a transition metal which participates generating oxygen free radicals, displays also this duality in infection. We suggest also that different infectious pathologies, such as sickle cell anemia/malaria and AIDS, may display in part this duality. In addition, it should be noted that oxidative damage observed in infectious diseases is mostly due the inflammatory response than to the oxidative potential of the pathogenic agent, this last point is exemplified in cases of respiratory distress and in glomerulonephritis. This review analyzes these controversial facts of infectious pathology in relation with oxidative stress.

Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress.

PubMed

Bettio, Luis E B; Freitas, Andiara E; Neis, Vivian B; Santos, Danúbia B; Ribeiro, Camille M; Rosa, Priscila B; Farina, Marcelo; Rodrigues, Ana Lúcia S

2014-12-01

Guanosine is a guanine-based purine that modulates glutamate uptake and exerts neurotrophic and neuroprotective effects. In a previous study, our group demonstrated that this endogenous nucleoside displays antidepressant-like properties in a predictive animal model. Based on the role of oxidative stress in modulating depressive disorders as well as on the association between the neuroprotective and antioxidant properties of guanosine, here we investigated if its antidepressant-like effect is accompanied by a modulation of hippocampal oxidant/antioxidant parameters. Adult Swiss mice were submitted to an acute restraint stress protocol, which is known to cause behavioral changes that are associated with neuronal oxidative damage. Animals submitted to ARS exhibited an increased immobility time in the forced swimming test (FST) and the administration of guanosine (5mg/kg, p.o.) or fluoxetine (10mg/kg, p.o., positive control) before the exposure to stressor prevented this alteration. Moreover, the significantly increased levels of hippocampal malondialdehyde (MDA; an indicator of lipid peroxidation), induced by ARS were not observed in stressed mice treated with guanosine. Although no changes were found in the hippocampal levels of reduced glutathione (GSH), the group submitted to ARS procedure presented enhanced glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) activities and reduced catalase (CAT) activity in the hippocampus. Guanosine was able to prevent the alterations in GPx, GR, CAT activities, and in SOD/CAT activity ratio, but potentiated the increase in SOD activity elicited by ARS. Altogether, the present findings indicate that the observed antidepressant-like effects of guanosine might be related, at least in part, to its capability of modulating antioxidant defenses and mitigating hippocampal oxidative damage induced by ARS. Copyright © 2014 Elsevier Inc. All rights reserved.

Reproduction Does Not Adversely Affect Liver Mitochondrial Respiratory Function but Results in Lipid Peroxidation and Increased Antioxidants in House Mice.

PubMed

Mowry, Annelise V; Kavazis, Andreas N; Sirman, Aubrey E; Potts, Wayne K; Hood, Wendy R

2016-01-01

Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage.

Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis

NASA Astrophysics Data System (ADS)

Caputo, Fanny; de Nicola, Milena; Sienkiewicz, Andrzej; Giovanetti, Anna; Bejarano, Ignacio; Licoccia, Silvia; Traversa, Enrico; Ghibelli, Lina

2015-09-01

Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields.

Honest sexual signalling mediated by parasite and testosterone effects on oxidative balance.

PubMed

Mougeot, Francois; Martínez-Padilla, Jesús; Webster, Lucy M I; Blount, Jonathan D; Pérez-Rodríguez, Lorenzo; Piertney, Stuart B

2009-03-22

Extravagant ornaments evolved to advertise their bearers' quality, the honesty of the signal being ensured by the cost paid to produce or maintain it. The oxidation handicap hypothesis (OHH) proposes that a main cost of testosterone-dependent ornamentation is oxidative stress, a condition whereby the production of reactive oxygen and nitrogen species (ROS/RNS) overwhelms the capacity of antioxidant defences. ROS/RNS are unstable, very reactive by-products of normal metabolic processes that can cause extensive damage to key biomolecules (cellular proteins, lipids and DNA). Oxidative stress has been implicated in the aetiology of many diseases and could link ornamentation and genetic variation in fitness-related traits. We tested the OHH in a free-living bird, the red grouse. We show that elevated testosterone enhanced ornamentation and increased circulating antioxidant levels, but caused oxidative damage. Males with smaller ornaments suffered more oxidative damage than those with larger ornaments when forced to increase testosterone levels, consistent with a handicap mechanism. Parasites depleted antioxidant defences, caused oxidative damage and reduced ornament expression. Oxidative damage extent and the ability of males to increase antioxidant defences also explained the impacts of testosterone and parasites on ornamentation within treatment groups. Because oxidative stress is intimately linked to immune function, parasite resistance and fitness, it provides a reliable currency in the trade-off between individual health and ornamentation. The costs induced by oxidative stress can apply to a wide range of signals, which are testosterone-dependent or coloured by pigments with antioxidant properties.

Honest sexual signalling mediated by parasite and testosterone effects on oxidative balance

PubMed Central

Mougeot, Francois; Martínez-Padilla, Jesu´s; Webster, Lucy M.I.; Blount, Jonathan D.; Pérez-Rodríguez, Lorenzo; Piertney, Stuart B.

2008-01-01

Extravagant ornaments evolved to advertise their bearers' quality, the honesty of the signal being ensured by the cost paid to produce or maintain it. The oxidation handicap hypothesis (OHH) proposes that a main cost of testosterone-dependent ornamentation is oxidative stress, a condition whereby the production of reactive oxygen and nitrogen species (ROS/RNS) overwhelms the capacity of antioxidant defences. ROS/RNS are unstable, very reactive by-products of normal metabolic processes that can cause extensive damage to key biomolecules (cellular proteins, lipids and DNA). Oxidative stress has been implicated in the aetiology of many diseases and could link ornamentation and genetic variation in fitness-related traits. We tested the OHH in a free-living bird, the red grouse. We show that elevated testosterone enhanced ornamentation and increased circulating antioxidant levels, but caused oxidative damage. Males with smaller ornaments suffered more oxidative damage than those with larger ornaments when forced to increase testosterone levels, consistent with a handicap mechanism. Parasites depleted antioxidant defences, caused oxidative damage and reduced ornament expression. Oxidative damage extent and the ability of males to increase antioxidant defences also explained the impacts of testosterone and parasites on ornamentation within treatment groups. Because oxidative stress is intimately linked to immune function, parasite resistance and fitness, it provides a reliable currency in the trade-off between individual health and ornamentation. The costs induced by oxidative stress can apply to a wide range of signals, which are testosterone-dependent or coloured by pigments with antioxidant properties. PMID:19129122

Effect of short-term hazelnut consumption on DNA damage and oxidized LDL in children and adolescents with primary hyperlipidemia: a randomized controlled trial.

PubMed

Guaraldi, Federica; Deon, Valeria; Del Bo', Cristian; Vendrame, Stefano; Porrini, Marisa; Riso, Patrizia; Guardamagna, Ornella

2018-07-01

Children with primary hyperlipidemia are prone to develop premature atherosclerosis, possibly associated with increased oxidative stress. Nutritional therapy is the primary strategy in the treatment of hyperlipidemia and associated conditions. Dietary interventions with bioactive-rich foods, such as nuts, may contribute to the modulation of both lipid profile and the oxidative/antioxidant status. Our study aimed to assess the impact of a dietary intervention with hazelnuts on selected oxidative stress markers in children and adolescents with primary hyperlipidemia. A single-blind, 8-week, randomized, controlled, three-arm, parallel-group study was performed. Children and adolescents diagnosed with primary hyperlipidemia (n=60) received dietary guidelines and were randomized into three groups: group 1 received hazelnuts with skin (HZN+S), and group 2 hazelnuts without skin (HZN-S), at equivalent doses (15-30 g/day, based on body weight); group 3 (controls) received only dietary recommendations (no nuts). At baseline and after 8 weeks, plasma oxidized low-density lipoprotein (ox-LDL) concentrations, oxidative levels of DNA damage in PBMCs and potential correlation with changes in serum lipids were examined. A reduction of endogenous DNA damage by 18.9%±51.3% (P=.002) and 23.1%±47.9% (P=.007) was observed after HZN+S and HZN-S, respectively. Oxidatively induced DNA strand breaks decreased by 16.0%±38.2% (P=.02) following HZN+S treatment. Ox-LDL levels did not change after HZN+S intervention but positively correlated with total cholesterol and LDL cholesterol. A short-term hazelnut intervention improves cell DNA protection and resistance against oxidative stress but not ox-LDL in hyperlipidemic pediatric patients. The trial was registered at ISRCTN.com, ID no. ISRCTN12261900. Copyright © 2018 Elsevier Inc. All rights reserved.

Immunohistochemical and ELISA assays for biomarkers of oxidative stress in aging and disease.

PubMed

Onorato, J M; Thorpe, S R; Baynes, J W

1998-11-20

Oxidative stress is apparent in pathology associated with aging and many age-related, chronic diseases, including atherosclerosis, diabetes mellitus, rheumatoid arthritis, and neurodegenerative diseases. Although it cannot be measured directly in biological systems, several biomarkers have been identified that provide a measure of oxidative damage to biomolecules. These include amino acid oxidation products (methionine sulfoxide, ortho-tyrosine (o-tyr) and dityrosine, chlorotyrosine and nitrotyrosine), as well as chemical modifications of protein following carbohydrate or lipid oxidation, such as N epsilon-(carboxymethyl)lysine and N epsilon-(carboxyethyl)lysine, and malondialdehyde and 4-hydroxynonenal adducts to amino acids. Other biomarkers include the amino acid cross-link pentosidine, the imidazolone adducts formed by reaction of 3-deoxyglucosone or methylglyoxal with arginine, and the imidazolium cross-links formed by the reaction of glyoxal and methylglyoxal with lysine residues in protein. These compounds have been measured in short-lived intracellular proteins, plasma proteins, long-lived extracellular proteins, and in urine, making them valuable tools for monitoring tissue-specific and systemic chemical and oxidative damage to proteins in biological systems. They are normally measured by sensitive high-performance liquid chromatography or gas chromatography-mass spectrometry methods, requiring both complex analytical instrumentation and derivatization procedures. However, sensitive immunohistochemical and ELISA assays are now available for many of these biomarkers. Immunochemical assays should facilitate studies on the role of oxidative stress in aging and chronic disease and simplify the evaluation of therapeutic approaches for limiting oxidative damage in tissues and treating pathologies associated with aging and disease. In this article we summarize recent data and conclusions based on immunohistochemical and ELISA assays, emphasizing the strengths and limitations of the techniques.

Evaluating Metabolite-Related DNA Oxidation and Adduct Damage from Aryl Amines Using a Microfluidic ECL Array.

PubMed

Bist, Itti; Bhakta, Snehasis; Jiang, Di; Keyes, Tia E; Martin, Aaron; Forster, Robert J; Rusling, James F

2017-11-21

Damage to DNA from the metabolites of drugs and pollutants constitutes a major human toxicity pathway known as genotoxicity. Metabolites can react with metal ions and NADPH to oxidize DNA or participate in S N 2 reactions to form covalently linked adducts with DNA bases. Guanines are the main DNA oxidation sites, and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) is the initial product. Here we describe a novel electrochemiluminescent (ECL) microwell array that produces metabolites from test compounds and measures relative rates of DNA oxidation and DNA adduct damage. In this new array, films of DNA, metabolic enzymes, and an ECL metallopolymer or complex assembled in microwells on a pyrolytic graphite wafer are housed in dual microfluidic chambers. As reactant solution passes over the wells, metabolites form and can react with DNA in the films to form DNA adducts. These adducts are detected by ECL from a RuPVP polymer that uses DNA as a coreactant. Aryl amines also combine with Cu 2+ and NADPH to form reactive oxygen species (ROS) that oxidize DNA. The resulting 8-oxodG was detected selectively by ECL-generating bis(2,2'-bipyridine)-(4-(1,10-phenanthrolin-6-yl)-benzoic acid)Os(II). DNA/enzyme films on magnetic beads were oxidized similarly, and 8-oxodG determined by LC/MS/MS enabled array standardization. The array limit of detection for oxidation was 720 8-oxodG per 10 6 nucleobases. For a series of aryl amines, metabolite-generated DNA oxidation and adduct formation turnover rates from the array correlated very well with rodent 1/TD 50 and Comet assay results.

Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage.

PubMed

Yen, Ching-Yu; Hou, Ming-Feng; Yang, Zhi-Wen; Tang, Jen-Yang; Li, Kun-Tzu; Huang, Hurng-Wern; Huang, Yu-Hsuan; Lee, Sheng-Yang; Fu, Tzu-Fun; Hsieh, Che-Yu; Chen, Bing-Hung; Chang, Hsueh-Wei

2015-03-29

Grape seeds extract (GSE) is a famous health food supplement for its antioxidant property. Different concentrations of GSE may have different impacts on cellular oxidative/reduction homeostasis. Antiproliferative effect of GSE has been reported in many cancers but rarely in oral cancer. The aim of this study is to examine the antioral cancer effects of different concentrations of GSE in terms of cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial function, and DNA damage. High concentrations (50-400 μg/ml) of GSE dose-responsively inhibited proliferation of oral cancer Ca9-22 cells but low concentrations (1-10 μg/ml) of GSE showed a mild effect in a MTS assay. For apoptosis analyses, subG1 population and annexin V intensity in high concentrations of GSE-treated Ca9-22 cells was increased but less so at low concentrations. ROS generation and mitochondrial depolarization increased dose-responsively at high concentrations but showed minor changes at low concentrations of GSE in Ca9-22 cells. Additionally, high concentrations of GSE dose-responsively induced more γH2AX-based DNA damage than low concentrations. Differential concentrations of GSE may have a differentially antiproliferative function against oral cancer cells via differential apoptosis, oxidative stress and DNA damage.

Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

PubMed Central

2016-01-01

The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms. PMID:26949445

Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light.

PubMed

Zhang, Xiaohong; Jeffs, Graham; Ren, Xiaolin; O'Donovan, Peter; Montaner, Beatriz; Perrett, Conal M; Karran, Peter; Xu, Yao-Zhong

2007-03-01

The therapeutic effect of the thiopurines, 6-thioguanine (6-TG), 6-mercaptopurine, and its prodrug azathioprine, depends on the incorporation of 6-TG into cellular DNA. Unlike normal DNA bases, 6-TG absorbs UVA radiation, and UVA-mediated photochemical damage of DNA 6-TG has potentially harmful side effects. When free 6-TG is UVA irradiated in solution in the presence of molecular oxygen, reactive oxygen species are generated and 6-TG is oxidized to guanine-6-sulfonate (G(SO3)) and guanine-6-thioguanine in reactions involving singlet oxygen. This conversion is prevented by antioxidants, including the dietary vitamin ascorbate. DNA G(SO3) is also the major photoproduct of 6-TG in DNA and it can be selectively introduced into DNA or oligonucleotides in vitro by mild chemical oxidation. Thermal stability measurements indicate that G(SO3) does not form stable base pairs with any of the normal DNA bases in duplex oligonucleotides and is a powerful block for elongation by Klenow DNA polymerase in primer extension experiments. In cultured human cells, DNA damage produced by 6-TG and UVA treatment is associated with replication inhibition and provokes a p53-dependent DNA damage response.

Predicting storage-dependent damage to red blood cells using nitrite oxidation kinetics, peroxiredoxin-2 oxidation, and hemoglobin and free heme measurements.

PubMed

Oh, Joo-Yeun; Stapley, Ryan; Harper, Victoria; Marques, Marisa B; Patel, Rakesh P

2015-12-01

Storage-dependent damage to red blood cells (RBCs) varies significantly. Identifying RBC units that will undergo higher levels of hemolysis during storage may allow for more efficient inventory management decision-making. Oxidative-stress mediates storage-dependent damage to RBCs and will depend on the oxidant:antioxidant balance. We reasoned that this balance or redox tone will serve as a determinant of how a given RBC unit stores and that its assessment in "young" RBCs will predict storage-dependent hemolysis. RBCs were sampled from bags and segments stored for 7 to 42 days. Redox tone was assessed by nitrite oxidation kinetics and peroxiredoxin-2 (Prx-2) oxidation. In parallel, hemolysis was assessed by measuring cell-free hemoglobin (Hb) and free heme (hemin). Correlation analyses were performed to determine if Day 7 measurements predicted either the level of hemolysis at Day 35 or the increase in hemolysis during storage. Higher Day 7 Prx-2 oxidation was associated with higher Day 35 Prx-2 oxidation, suggesting that early assessment of this variable may identify RBCs that will incur the most oxidative damage during storage. RBCs that oxidized nitrite faster on Day 7 were associated with the greatest levels of storage-dependent hemolysis and increases in Prx-2 oxidation. An inverse relationship between storage-dependent changes in oxyhemoglobin and free heme was observed underscoring an unappreciated reciprocity between these molecular species. Moreover, free heme was higher in the bag compared to paired segments, with opposite trends observed for free Hb. Measurement of Prx-2 oxidation and nitrite oxidation kinetics early during RBC storage may predict storage-dependent damage to RBC including hemolysis-dependent formation of free Hb and heme. © 2015 AABB.

A Novel Drug Delivery Vesicle Development to Reverse Neurodegeneration: Analysis of the Interactions among Protein, Graphene Oxide and Liposome

NASA Astrophysics Data System (ADS)

Miraz, Md Alamin

In this study, Liposome was decorated with graphene oxide (GO) to synthesize fully-biocompatible theranostic vesicle that can carry bovine serum albumin (BSA) as a model protein. Graphene oxide has been studied as one of the most promising platforms for promoting the growth and repair of neurons. Our graphene oxide based structure could account for the high efficiency of protein loading and deliver to the damaged neuron cell which can reverse the neurodegeneration associated with Alzheimer's disease. The resultant vesicle exhibited high stability in aqueous solution. We investigated the protein adsorption capacity and protein interaction to carbon-based nanomaterials. The Liposome, graphene oxide and bovine serum albumin (BSA) are all biocompatible and hence will not trigger an immune response in vivo.

Watson-Crick Base Pair Radical Cation as a Model for Oxidative Damage in DNA.

PubMed

Feketeová, Linda; Chan, Bun; Khairallah, George N; Steinmetz, Vincent; Maitre, Philippe; Radom, Leo; O'Hair, Richard A J

2017-07-06

The deleterious cellular effects of ionizing radiation are well-known, but the mechanisms causing DNA damage are poorly understood. The accepted molecular events involve initial oxidation and deprotonation at guanine sites, triggering hydrogen atom abstraction reactions from the sugar moieties, causing DNA strand breaks. Probing the chemistry of the initially formed radical cation has been challenging. Here, we generate, spectroscopically characterize, and examine the reactivity of the Watson-Crick nucleobase pair radical cation in the gas phase. We observe rich chemistry, including proton transfer between the bases and propagation of the radical site in deoxyguanosine from the base to the sugar, thus rupturing the sugar. This first example of a gas-phase model system providing molecular-level details on the chemistry of an ionized DNA base pair paves the way toward a more complete understanding of molecular processes induced by radiation. It also highlights the role of radical propagation in chemistry, biology, and nanotechnology.

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

PubMed

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

2005-07-28

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

Relative contribution of homologous recombination and non-homologous end-joining to DNA double-strand break repair after oxidative stress in Saccharomyces cerevisiae.

PubMed

Letavayová, Lucia; Marková, Eva; Hermanská, Katarína; Vlcková, Viera; Vlasáková, Danusa; Chovanec, Miroslav; Brozmanová, Jela

2006-05-10

Oxidative damage to DNA seems to be an important factor in developing many human diseases including cancer. It involves base and sugar damage, base-free sites, DNA-protein cross-links and DNA single-strand (SSB) and double-strand (DSB) breaks. Oxidative DSB can be formed in various ways such as their direct induction by the drug or their generation either through attempted and aborted repair of primary DNA lesions or through DNA replication-dependent conversion of SSB. In general, two main pathways are responsible for repairing DSB, homologous recombination (HR) and non-homologous end-joining (NHEJ), with both of them being potential candidates for the repair of oxidative DSB. We have examined relative contribution of HR and NHEJ to cellular response after oxidative stress in Saccharomyces cerevisiae. Therefore, cell survival, mutagenesis and DSB induction and repair in the rad52, yku70 and rad52 yku70 mutants after hydrogen peroxide (H(2)O(2)), menadione (MD) or bleomycin (BLM) exposure were compared to those obtained for the corresponding wild type. We show that MD exposure does not lead to observable DSB induction in yeast, suggesting that the toxic effects of this agent are mediated by other types of DNA damage. Although H(2)O(2) treatment generates some DSB, their yield is relatively low and hence DSB may only partially be responsible for toxicity of H(2)O(2), particularly at high doses of the agent. On the other hand, the basis of the BLM toxicity resides primarily in DSB induction. Both HR and NHEJ act on BLM-induced DSB, although their relative participation in the process is not equal. Based on our results we suggest that the complexity and/or the quality of the BLM-induced DSB might represent an obstacle for the NHEJ pathway.

[Increasing oxidative stress in aging].

PubMed

Shimosawa, Tatsuo

2005-06-01

The balance between reactive oxigen species (ROS) production and degradation is important in defining oxidative stress. In aging process, ROS production increases and degradation is impaired and thus oxidative stress is accumulated. Oxidative stress damages organs both directly and indirectly. Protein, lipid, as well as DNA are directly react with ROS, more over, ROS interact with intracellular signaling system. It is reported that several transcription factors such as NF-kappaB, AP-1 and ASK-1 and also it interferes MAPK activity. Besides these signaling, we recently showed that insulin resistance is induced by accumulated oxidative stress in aged mice. Adrenomedullin deficient mice accumulate higher oxidative stress and insulin resistance developed in aging. Oxidative stress in aging relates not only direct organ damage but also induce risk factors for vascular damage such as metabolic syndrome.

Cryopreservation of human blood for alkaline and Fpg-modified comet assay.

PubMed

Pu, Xinzhu; Wang, Zemin; Klaunig, James E

2016-01-01

The Comet assay is a reproducible and sensitive assay for the detection of DNA damage in eukaryotic cells and tissues. Incorporation of lesion specific, oxidative DNA damage repair enzymes (for example, Fpg, OGG1 and EndoIII) in the standard alkaline Comet assay procedure allows for the detection and measurement of oxidative DNA damage. The Comet assay using white blood cells (WBC) has proven useful in monitoring DNA damage from environmental agents in humans. However, it is often impractical to performance Comet assay immediately after blood sampling. Thus, storage of blood sample is required. In this study, we developed and tested a simple storage method for very small amount of whole blood for standard and Fpg-modified modified Comet assay. Whole blood was stored in RPMI 1640 media containing 10% FBS, 10% DMSO and 1 mM deferoxamine at a sample to media ratio of 1:50. Samples were stored at -20 °C and -80 °C for 1, 7, 14 and 28 days. Isolated lymphocytes from the same subjects were also stored under the same conditions for comparison. Direct DNA strand breakage and oxidative DNA damage in WBC and lymphocytes were analyzed using standard and Fpg-modified alkaline Comet assay and compared with freshly analyzed samples. No significant changes in either direct DNA strand breakage or oxidative DNA damage was seen in WBC and lymphocytes stored at -20 °C for 1 and 7 days compared to fresh samples. However, significant increases in both direct and oxidative DNA damage were seen in samples stored at -20 °C for 14 and 28 days. No changes in direct and oxidative DNA damage were observed in WBC and lymphocytes stored at -80 °C for up to 28 days. These results identified the proper storage conditions for storing whole blood or isolated lymphocytes to evaluate direct and oxidative DNA damage using standard and Fpg-modified alkaline Comet assay.

Clustered DNA damages induced by high and low LET radiation, including heavy ions

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

2001-01-01

Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

Recommendations for standardised description of, and nomenclature concerning, oxidatively damaged nucleobases in DNA

PubMed Central

Cooke, Marcus S.; Loft, Steffen; Olinski, Ryszard; Evans, Mark D.; Bialkowski, Karol; Wagner, J. Richard; Dedon, Peter C.; Møller, Peter; Greenberg, Marc M.; Cadet, Jean

2013-01-01

The field of oxidative stress, and the study of oxidatively damaged DNA, in particular, is a subject of intense, and growing interest. This has, in part, benefited from the availability of kits from commercial suppliers which are advertised as reporting on markers of oxidative stress. Such widespread use has inevitably led to an increase in the number of concerns, amongst experts in the field, editors and referees, over appropriateness of terminology and methodology. Thus, the widely used term “oxidative DNA damage” is misleading as it implies that the damage, i.e. the lesion per se, is oxidative and thus capable of oxidising other substrates. We would encourage the use of such terms as ‘oxidatively damaged DNA’, ‘oxidatively generated DNA damage’, ‘oxidatively-derived damage to DNA’ or ‘oxidation-induced DNA damage’ to describe the consequence of the interaction of reactive oxygen species with DNA. One of the most studied nucleic acid-derived biomarkers of oxidative stress is 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Yet, in the literature, this compound has been referred to using a number of different terms, sometimes leading to confusion over the designation of the modified nucleobase or (2′-deoxy)ribonucleoside. Standardisation of nomenclature would not only simplify literature searches, but also clarify the lesion in question. Herein, we provide justification for our preferred nomenclature, and suggest a number of steps by which we may work towards standardisation of calibration, and with it improved inter-laboratory agreement, for assays of 8-oxodG, in order to achieve accurate measurements. PMID:20235554

Oxidative Damage and Mitochondrial Injuries Are Induced by Various Irrigation Pressures in Rabbit Models of Mild and Severe Hydronephrosis

PubMed Central

Cao, Zhixiu; Yu, Weimin; Li, Wei; Cheng, Fan; Rao, Ting; Yao, Xiaobing; Zhang, Xiaobin; Larré, Stéphane

2015-01-01

Objective We aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis. Methods A total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24) or severe (group S, n=24) hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3) consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL). Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD) activity, malondialdehyde (MDA) levels, glutathione reductase (GR), catalase (CAT) and peroxide (H2O2) levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP), the mitochondrial ultrastructure and tubular cell apoptosis. Results In the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index. Conclusion In rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure. PMID:26090815

No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

PubMed

Mahabir, S; Baer, D J; Johnson, L L; Frenkel, K; Dorgan, J F; Cambell, W; Hartman, T J; Clevidence, B; Albanes, D; Judd, J T; Taylor, P R

2005-08-01

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

Evaluation of basal DNA damage and oxidative stress in Wistar rat leukocytes after exposure to microwave radiation.

PubMed

Garaj-Vrhovac, Vera; Gajski, Goran; Trosić, Ivancica; Pavicić, Ivan

2009-05-17

The aim of this study was to assess whether microwave-induced DNA damage is basal or it is also generated through reactive oxygen species (ROS) formation. After having irradiated Wistar rats with 915MHz microwave radiation, we assessed different DNA alterations in peripheral leukocytes using standard and formamidopyrimidine DNA-glycosylase (Fpg)-modified comet assay. The first is a sensitive tool for detecting primary DNA damage, and the second is much more specific for detecting oxidative damage. The animals were irradiated for 1h a day for 2 weeks at a field power density of 2.4W/m(2), and the whole-body average specific absorption rate (SAR) of 0.6W/kg. Both the standard and the Fpg-modified comet assay detected increased DNA damage in blood leukocytes of the exposed rats. The significant increase in Fpg-detected DNA damage in the exposed rats suggests that oxidative stress is likely to be responsible. DNA damage detected by the standard comet assay indicates that some other mechanisms may also be involved. In addition, both methods served proved sensitive enough to measure basal and oxidative DNA damage after long-term exposure to 915MHz microwave radiation in vivo.

Protective Role for Antioxidants in Acute Kidney Disease

PubMed Central

Dennis, Joanne M.; Witting, Paul K.

2017-01-01

Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status. PMID:28686196

Oxidant-induced DNA damage of target cells.

PubMed Central

Schraufstätter, I; Hyslop, P A; Jackson, J H; Cochrane, C G

1988-01-01

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks. PMID:2843565

Physical exercise and oxidative stress in muscular dystrophies: is there a good balance?

PubMed

Chico, L; Ricci, G; Cosci O Di Coscio, M; Simoncini, C; Siciliano, G

2017-07-01

The effect of oxidative stress on muscle damage inducted by physical exercise is widely debated. It is generally agreed that endurance and intense exercise can increase oxidative stress and generate changes in antioxidant power inducing muscle damage; however, regular and moderate exercise can be beneficial for the health improving the antioxidant defense mechanisms in the majority of cases. Growing evidences suggest that an increased oxidative/nitrosative stress is involved in the pathogenesis of several muscular dystrophies (MDs). Notably, physical training has been considered useful for patients with these disorders. This review will focus on the involvement of oxidative stress in MDs and on the possible effects of physical activities to decrease oxidative damage and improve motor functions in MDs patients.

BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1.

PubMed

Yang, Jenq-Lin; Lin, Yu-Ting; Chuang, Pei-Chin; Bohr, Vilhelm A; Mattson, Mark P

2014-03-01

Brain-derived neurotrophic factor (BDNF) promotes the survival and growth of neurons during brain development and mediates activity-dependent synaptic plasticity and associated learning and memory in the adult. BDNF levels are reduced in brain regions affected in Alzheimer's, Parkinson's, and Huntington's diseases, and elevation of BDNF levels can ameliorate neuronal dysfunction and degeneration in experimental models of these diseases. Because neurons accumulate oxidative lesions in their DNA during normal activity and in neurodegenerative disorders, we determined whether and how BDNF affects the ability of neurons to cope with oxidative DNA damage. We found that BDNF protects cerebral cortical neurons against oxidative DNA damage-induced death by a mechanism involving enhanced DNA repair. BDNF stimulates DNA repair by activating cyclic AMP response element-binding protein (CREB), which, in turn, induces the expression of apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision DNA repair pathway. Suppression of either APE1 or TrkB by RNA interference abolishes the ability of BDNF to protect neurons against oxidized DNA damage-induced death. The ability of BDNF to activate CREB and upregulate APE1 expression is abolished by shRNA of TrkB as well as inhibitors of TrkB, PI3 kinase, and Akt kinase. Voluntary running wheel exercise significantly increases levels of BDNF, activates CREB, and upregulates APE1 in the cerebral cortex and hippocampus of mice, suggesting a novel mechanism whereby exercise may protect neurons from oxidative DNA damage. Our findings reveal a previously unknown ability of BDNF to enhance DNA repair by inducing the expression of the DNA repair enzyme APE1.

Adaptation of rat gastric tissue against indomethacin toxicity.

PubMed

Polat, Beyzagul; Suleyman, Halis; Alp, Hamit Hakan

2010-06-07

Indomethacin is used in the treatment of inflammatory diseases. But the drug toxicity limits its usage. This study investigated whether adaptation occurred after various dosages of repeated (chronic) indomethacin in rats to the gastro-toxic effects of indomethacin. It also examined whether the adaptation was related to oxidant-antioxidant mechanisms and oxidative DNA damage in gastric tissue. To illuminate the adaptation mechanism in the gastric tissue of rats given various dosages of chronic indomethacin, the levels of oxidants and antioxidants (GSH, MDA, NO, SOD and MPO), activities of COX-1 and COX-2 enzymes and oxidative DNA damage (8-OHd Gua/10(5) Gua) were measured. Results were compared to 25-mg/kg single-dose indomethacin group, and the role of oxidant and antioxidant parameters and oxidative DNA damage in the adaptation mechanism was evaluated. The average ulcer areas of gastric tissue of the 0.5-, 1-, 2-, 3-, 4-, and 5-mg/kg dosages of chronic indomethacin given to rats were 19.5+/-3.7, 12.5+/-3.3, 10+/-5.2, 4.5+/-3.6, 8.6+/-2.4, and 9.5+/-2.1mm(2), respectively. This rate was measured as 21.3+/-2.6mm(2) in the single-dose indomethacin group. Consequently, after various dosages of repeated (chronic) indomethacin administration in rats, it was observed that a clear adaptation developed against gastric damage and that gastric damage was reduced. The best adaptation was observed in the gastric tissue of the 3-mg/kg chronic indomethacin group. In parallel with the damage reduction, the oxidant parameters (MDA and MPO) and oxidative DNA damage (8-OHd Gua/10(5) Gua) were reduced, and the antioxidant parameters (GSH, NO and SOD) were increased. There is no relation between COX enzymes and adaptation mechanism. This circumstance shows that not COX-1 and COX-2 enzymes, oxidant and antioxidant parameters may play a role in the adaptation mechanism. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Co-exposure to polycyclic aromatic hydrocarbons, benzene and toluene and their dose-effects on oxidative stress damage in kindergarten-aged children in Guangzhou, China.

PubMed

Li, Junnan; Lu, Shaoyou; Liu, Guihua; Zhou, Yuanxiu; Lv, Yanshan; She, Jianwen; Fan, Ruifang

2015-08-15

Polycyclic aromatic hydrocarbons (PAHs), benzene and toluene (BT) are ubiquitous toxic pollutants in the environment. Children are sensitive and susceptible to exposure to these contaminants. To investigate the potential oxidative DNA damage from the co-exposure of PAHs and BT in children, 87 children (aged 3-6) from a kindergarten in Guangzhou, China, were recruited. Ten urinary PAHs and four BT metabolites, as well as 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage)in urine, were determined using a liquid chromatography tandem mass spectrometer. The results demonstrated that the levels of PAHs and BT in children from Guangzhou were 2-30 times higher than those in children from the other countries based on a comparison with recent data from the literature. In particular, the difference is more substantial for pyrene and volatile BT. Co-exposure to PAHs and BT could lead to additive oxidative DNA damage. Significant dose-effects were observed between the sum concentration of urinary monohydroxylated metabolites of PAHs (∑OH-PAHs), the sum concentration of the metabolites of BT (∑BT) and 8-OHdG levels. Every one percent increase in urinary PAHs and BT generated 0.33% and 0.02% increases in urinary 8-OHdG, respectively. We also determined that the urinary levels of PAHs and BT were negatively associated with the age of the children. Moreover, significant differences in the levels of ∑OH-PAHs and ∑BT were determined between 3- and 6-year-old children (p<0.05), which may be caused by different metabolism capabilities or inhalation frequencies. In conclusion, exposure to PAHs or BT could lead to oxidative DNA damage, and 8-OHdG is a good biomarker for indicating the presence of DNA damage. There exists a significant dose-effect relationship between PAH exposure, BT exposure and the concentration of 8-OHdG in urine. Toddlers (3-4 years old) face a higher burden of PAH and BT exposure compared with older children. Copyright © 2015 Elsevier B.V. All rights reserved.

Is reproduction costly? No increase of oxidative damage in breeding bank voles.

PubMed

Ołdakowski, Łukasz; Piotrowska, Zaneta; Chrzaácik, Katarzyna M; Sadowska, Edyta T; Koteja, Paweł; Taylor, Jan R E

2012-06-01

According to life-history theory, investment in reproduction is associated with costs, which should appear as decreased survival to the next reproduction or lower future reproductive success. It has been suggested that oxidative stress may be the proximate mechanism of these trade-offs. Despite numerous studies of the defense against reactive oxygen species (ROS) during reproduction, very little is known about the damage caused by ROS to the tissues of wild breeding animals. We measured oxidative damage to lipids and proteins in breeding bank vole (Myodes glareolus) females after rearing one and two litters, and in non-breeding females. We used bank voles from lines selected for high maximum aerobic metabolic rates (which also had high resting metabolic rates and food intake) and non-selected control lines. The oxidative damage was determined in heart, kidneys and skeletal muscles by measuring the concentration of thiobarbituric acid-reactive substances, as markers of lipid peroxidation, and carbonyl groups in proteins, as markers of protein oxidation. Surprisingly, we found that the oxidative damage to lipids in kidneys and muscles was actually lower in breeding than in non-breeding voles, and it did not differ between animals from the selected and control lines. Thus, contrary to our predictions, females that bred suffered lower levels of oxidative stress than those that did not reproduce. Elevated production of antioxidant enzymes and the protective role of sex hormones may explain the results. The results of the present study do not support the hypothesis that oxidative damage to tissues is the proximate mechanism of reproduction costs.

An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands.

PubMed

Weisel, Tamara; Baum, Matthias; Eisenbrand, Gerhard; Dietrich, Helmut; Will, Frank; Stockis, Jean-Pierre; Kulling, Sabine; Rüfer, Corinna; Johannes, Christian; Janzowski, Christine

2006-04-01

Oxidative cell damage is involved in the pathogenesis of atherosclerosis, cancer, diabetes and other diseases. Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols, might reduce oxidative cell damage. Therefore, an intervention study was performed with a red mixed berry juice [trolox equivalent antioxidative capacity (TEAC): 19.1 mmol/L trolox] and a corresponding polyphenol-depleted juice (polyphenols largely removed, TEAC 2.4 mmol/L trolox), serving as control. After a 3-week run-in period, 18 male probands daily consumed 700 mL juice, and 9 consumed control juice, in a 4-week intervention, followed by a 3-week wash-out. Samples were collected weekly to analyze DNA damage (comet assay), lipid peroxidation (plasma malondialdehyde: HPLC/fluorescence; urinary isoprostanes: GC-MS), blood glutathione (photometrically), DNA-binding activity of nuclear factor-kappaB (ELISA) and plasma carotenoid/alpha-tocopherol levels (HPLC-DAD). During intervention with the fruit juice, a decrease of oxidative DNA damage (p<5x10(-4)) and an increase of reduced glutathione (p<5x10(-4)) and of glutathione status (p<0.05) were observed, which returned to the run-in levels in the subsequent wash-out phase. The other biomarkers were not significantly modulated by the juice supplement. Intervention with the control juice did not result in reduction of oxidative damage. In conclusion, the fruit juice clearly reduces oxidative cell damage in healthy probands.

Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury.

PubMed

Adlam, Victoria J; Harrison, Joanne C; Porteous, Carolyn M; James, Andrew M; Smith, Robin A J; Murphy, Michael P; Sammut, Ivan A

2005-07-01

Mitochondrial oxidative damage contributes to a wide range of pathologies, including cardiovascular disorders and neurodegenerative diseases. Therefore, protecting mitochondria from oxidative damage should be an effective therapeutic strategy. However, conventional antioxidants have limited efficacy due to the difficulty of delivering them to mitochondria in situ. To overcome this problem, we developed mitochondria-targeted antioxidants, typified by MitoQ, which comprises a lipophilic triphenylphosphonium (TPP) cation covalently attached to a ubiquinol antioxidant. Driven by the large mitochondrial membrane potential, the TPP cation concentrates MitoQ several hundred-fold within mitochondria, selectively preventing mitochondrial oxidative damage. To test whether MitoQ was active in vivo, we chose a clinically relevant form of mitochondrial oxidative damage: cardiac ischemia-reperfusion injury. Feeding MitoQ to rats significantly decreased heart dysfunction, cell death, and mitochondrial damage after ischemia-reperfusion. This protection was due to the antioxidant activity of MitoQ within mitochondria, as an untargeted antioxidant was ineffective and accumulation of the TPP cation alone gave no protection. Therefore, targeting antioxidants to mitochondria in vivo is a promising new therapeutic strategy in the wide range of human diseases such as Parkinson's disease, diabetes, and Friedreich's ataxia where mitochondrial oxidative damage underlies the pathology.

Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension

PubMed Central

Chen, Pin-I; Cao, Aiqin; Miyagawa, Kazuya; Tojais, Nancy F.; Hennigs, Jan K.; Li, Caiyun G.; Sweeney, Nathaly M.; Inglis, Audrey S.; Wang, Lingli; Li, Dan; Ye, Matthew; Feldman, Brian J.

2017-01-01

Amphetamine (AMPH) or methamphetamine (METH) abuse can cause oxidative damage and is a risk factor for diseases including pulmonary arterial hypertension (PAH). Pulmonary artery endothelial cells (PAECs) from AMPH-associated-PAH patients show DNA damage as judged by γH2AX foci and DNA comet tails. We therefore hypothesized that AMPH induces DNA damage and vascular pathology by interfering with normal adaptation to an environmental perturbation causing oxidative stress. Consistent with this, we found that AMPH alone does not cause DNA damage in normoxic PAECs, but greatly amplifies DNA damage in hypoxic PAECs. The mechanism involves AMPH activation of protein phosphatase 2A, which potentiates inhibition of Akt. This increases sirtuin 1, causing deacetylation and degradation of HIF1α, thereby impairing its transcriptional activity, resulting in a reduction in pyruvate dehydrogenase kinase 1 and impaired cytochrome c oxidase 4 isoform switch. Mitochondrial oxidative phosphorylation is inappropriately enhanced and, as a result of impaired electron transport and mitochondrial ROS increase, caspase-3 is activated and DNA damage is induced. In mice given binge doses of METH followed by hypoxia, HIF1α is suppressed and pulmonary artery DNA damage foci are associated with worse pulmonary vascular remodeling. Thus, chronic AMPH/METH can induce DNA damage associated with vascular disease by subverting the adaptive responses to oxidative stress. PMID:28138562

Hypocaloric diet and regular moderate aerobic exercise is an effective strategy to reduce anthropometric parameters and oxidative stress in obese patients.

PubMed

Gutierrez-Lopez, Liliana; Garcia-Sanchez, Jose Ruben; Rincon-Viquez, Maria de Jesus; Lara-Padilla, Eleazar; Sierra-Vargas, Martha P; Olivares-Corichi, Ivonne M

2012-01-01

Studies show that diet and exercise are important in the treatment of obesity. The aim of this study was to determine whether additional regular moderate aerobic exercise during a treatment with hypocaloric diet has a beneficial effect on oxidative stress and molecular damage in the obese patient. Oxidative stress of 16 normal-weight (NW) and 32 obese 1 (O1) subjects (BMI 30-34.9 kg/m(2)) were established by biomarkers of oxidative stress in plasma. Recombinant human insulin was incubated with blood from NW or O1 subjects, and the molecular damage to the hormone was analyzed. Two groups of treatment, hypocaloric diet (HD) and hypocaloric diet plus regular moderate aerobic exercise (HDMAE), were formed, and their effects in obese subjects were analyzed. The data showed the presence of oxidative stress in O1 subjects. Molecular damage and polymerization of insulin was observed more frequently in the blood from O1 subjects. The treatment of O1 subjects with HD decreased the anthropometric parameters as well as oxidative stress and molecular damage, which was more effectively prevented by the treatment with HDMAE. HD and HDMAE treatments decreased anthropometric parameters, oxidative stress, and molecular damage in O1 subjects. Copyright © 2012 S. Karger GmbH, Freiburg.

Neuroprotective activity of galloylated cyanogenic glucosides and hydrolysable tannins isolated from leaves of Phyllagathis rotundifolia.

PubMed

Tan, Hooi Poay; Wong, Daniel Zin Hua; Ling, Sui Kiong; Chuah, Cheng Hock; Kadir, Habsah Abdul

2012-01-01

The galloylated cyanogenic glucosides based on prunasin (1-7), gallotannins (8-14), ellagitannins (15-17), ellagic acid derivatives (18, 19) and gallic acid (20) isolated from the leaves of Phyllagathis rotundifolia (Melastomataceae) were investigated for their neuroprotective activity against hydrogen peroxide (H(2)O(2))-induced oxidative damage in NG108-15 hybridoma cell line. Among these compounds, the gallotannins and ellagitannins exhibited remarkable neuroprotective activities against oxidative damage in vitro as compared to galloylated cyanogenic glucosides and ellagic acid derivatives in a dose-dependent manner. They could be explored further as potential natural neuroprotectors in various remedies of neurodegenerative diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

Assessment of DNA damage using comet assay in middle-aged overweight/obese subjects after following a hypocaloric diet supplemented with cocoa extract.

PubMed

Ibero-Baraibar, Idoia; Azqueta, Amaya; Lopez de Cerain, Adela; Martinez, J Alfredo; Zulet, M Angeles

2015-01-01

Nutrient excess and unbalanced diets can result in overproduction of reactive oxygen species (ROS), which are associated with oxidative stress. Cocoa extract contains antioxidants that inhibit the harmful effects of ROS. This trial analysed the effect of cocoa extract consumption integrated as a bioactive compound into ready-to-eat meals, on oxidative stress at the level of DNA in overweight/obese subjects. Fifty volunteers [57.26(5.24) years, 30.59(2.33)kg/m(2)] participated in a 4-week double-blind, randomised, placebo-controlled parallel nutritional intervention. Half of the volunteers received meals supplemented with 1.4 g/day cocoa extract, while the other half received control meals, both within a 15% energy restriction diet. Lymphocytes were isolated and endogenous strand breaks, oxidised bases and resistance to H2O2-induced damage were measured by the comet assay. The intake of ready-to-eat meals supplemented with cocoa extract did not show relevant changes in the oxidative status of DNA. However, in the cocoa group, oxidised bases negatively correlated with methyl epicatechin-O-sulphate (r = -0.76; P = -0.007) and epicatechin sulphate (r = -0.61; P = -0.046). When volunteers of both groups were analysed together, a marginal decrease (P = 0.072) in oxidised bases was observed, which attributed to weight loss. Subjects who started the intervention with higher levels of damage showed a greater reduction in oxidised bases after 4 weeks (P = 0.040) compared to those who had lower baseline levels. In conclusion, even if 1.4 g of cocoa supplementation for 4 weeks did not show notable changes in terms of antioxidant status of DNA, the energy restriction showed a slightly decrease in oxidised bases and this was seen to a greater extent in subjects who started the intervention with higher levels of damage. On the other hand, the inverse associations found between oxidised bases and some cocoa-derived metabolites suggest that a protective effect might be seen in a longer period of time or in subjects with higher baseline DNA damage. www.clinicaltrials.gov (NCT01596309). © The Author 2014. Published by Oxford University Press on behalf of the Mutagenesis Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Base Excision Repair

PubMed Central

Krokan, Hans E.; Bjørås, Magnar

2013-01-01

Base excision repair (BER) corrects DNA damage from oxidation, deamination and alkylation. Such base lesions cause little distortion to the DNA helix structure. BER is initiated by a DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site that is further processed by short-patch repair or long-patch repair that largely uses different proteins to complete BER. At least 11 distinct mammalian DNA glycosylases are known, each recognizing a few related lesions, frequently with some overlap in specificities. Impressively, the damaged bases are rapidly identified in a vast excess of normal bases, without a supply of energy. BER protects against cancer, aging, and neurodegeneration and takes place both in nuclei and mitochondria. More recently, an important role of uracil-DNA glycosylase UNG2 in adaptive immunity was revealed. Furthermore, other DNA glycosylases may have important roles in epigenetics, thus expanding the repertoire of BER proteins. PMID:23545420

Mice Deficient in Both Mn Superoxide Dismutase and Glutathione Peroxidase-1 Have Increased Oxidative Damage and a Greater Incidence of Pathology but No Reduction in Longevity

PubMed Central

Zhang, Yiqiang; Ikeno, Yuji; Qi, Wenbo; Chaudhuri, Asish; Li, Yan; Bokov, Alex; Thorpe, Suzanne R.; Baynes, John W.; Epstein, Charles; Richardson, Arlan

2009-01-01

To test the impact of increased mitochondrial oxidative stress as a mechanism underlying aging and age-related pathologies, we generated mice with a combined deficiency in two mitochondrial-localized antioxidant enzymes, Mn superoxide dismutase (MnSOD) and glutathione peroxidase-1 (Gpx-1). We compared life span, pathology, and oxidative damage in Gpx1−/−, Sod2+/−Gpx1+/−, Sod2+/−Gpx1−/−, and wild-type control mice. Oxidative damage was elevated in Sod2+/−Gpx1−/− mice, as shown by increased DNA oxidation in liver and skeletal muscle and increased protein oxidation in brain. Surprisingly, Sod2+/−Gpx1−/− mice showed no reduction in life span, despite increased levels of oxidative damage. Consistent with the important role for oxidative stress in tumorigenesis during aging, the incidence of neoplasms was significantly increased in the older Sod2+/−Gpx1−/− mice (28–30 months). Thus, these data do not support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice and do not support the oxidative stress theory of aging. PMID:19776219

Development of HSPA1A promoter-driven luciferase reporter gene assays in human cells for assessing the oxidative damage induced by silver nanoparticles

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

Xin, Lili, E-mail: llxin@suda.edu.cn

The exponential increase in the total number of engineered nanoparticles in consumer products requires novel tools for rapid and cost-effective toxicology screening. In order to assess the oxidative damage induced by nanoparticles, toxicity test systems based on a human HSPA1A promoter-driven luciferase reporter in HepG2, LO2, A549, and HBE cells were established. After treated with heat shock and a group of silver nanoparticles (AgNPs) with different primary particle sizes, the cell viability, oxidative damage, and luciferase activity were determined. The time-dependent Ag{sup +} ions release from AgNPs in cell medium was also evaluated. Our results showed that heat shock producedmore » a strong time-dependent induction of relative luciferase activity in the four luciferase reporter cells. Surprisingly, at 4 h of recovery, the relative luciferase activity was > 98 × the control level in HepG2-luciferase cells. Exposure to different sizes of AgNPs resulted in activation of the HSPA1A promoter in a dose-dependent manner, even at low cytotoxic or non-cytotoxic doses. The smaller (5 nm) AgNPs were more potent in luciferase induction than the larger (50 and 75 nm) AgNPs. These results were generally in accordance with the oxidative damage indicated by malondialdehyde concentration, reactive oxygen species induction and glutathione depletion, and Ag{sup +} ions release in cell medium. Compared with the other three luciferase reporter cells, the luciferase signal in HepG2-luciferase cells is obviously more sensitive and stable. We conclude that the luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the oxidative damage induced by AgNPs. - Highlights: • We established the stable HSPA1A promoter-driven luciferase reporter cells. • Silver nanoparticles induced dose-dependent increases in luciferase activity. • HSPA1A promoter activity is a sensitive and responsive indicator of oxidative stress. • HepG2-luciferase cells can be used to assess the toxicity of silver nanoparticles.« less

The protective effect of menhaden oil in the oxidative damage and renal necrosis due to dietary choline deficiency.

PubMed

Ossani, Georgina P; Repetto, Marisa G; Boveris, Alberto; Monserrat, Alberto J

2013-02-26

Weanling rats fed a choline-deficient diet develop kidney oxidative damage, tubular and cortical kidney necrosis, renal failure and animal death. The effect of dietary menhaden oil was assayed on the mentioned sequence correlating oxidative stress with renal structure and function. Rats were fed ad libitum 4 different diets: (a) a choline-deficient diet with corn oil and sunflower hydrogenated oil as a source of fatty acids; (b) the same diet supplemented with choline; (c) a choline-deficient diet with menhaden oil as a source of fatty acids; and (d) the previous diet supplemented with choline. Animals were sacrificed at days 0, 2, 4 and 7. The histopathological study of the kidneys showed that renal necrosis was only observed at day 7 in choline-deficient rats receiving the vegetable oil diet, simultaneously with increased creatinine plasma levels. Homogenate chemiluminescence (BOOH-initiated chemiluminescence) and phospholipid oxidation indicate the development of oxidative stress and damage in choline-deficient rats fed vegetable oils as well as the protective effect of menhaden oil. Rats fed with the fish oil diet showed that oxidative stress and damage develop later, as compared with vegetable oil, with no morphological damage during the experimental period.

Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

PubMed

Morales-Martínez, Adriana; Sánchez-Mendoza, Alicia; Martínez-Lazcano, Juan Carlos; Pineda-Farías, Jorge Baruch; Montes, Sergio; El-Hafidi, Mohammed; Martínez-Gopar, Pablo Eliasib; Tristán-López, Luis; Pérez-Neri, Iván; Zamorano-Carrillo, Absalom; Castro, Nelly; Ríos, Camilo; Pérez-Severiano, Francisca

2017-09-01

Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells.

PubMed

Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

2015-11-01

Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin interact with UVA radiation to generate reactive oxygen species that diminish NER capacity by causing protein damage. The replication protein A (RPA) DNA-binding protein has a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation, and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage, and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself, is likely to be an important contributor to skin cancer risk.

Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?

PubMed Central

Halliwell, Barry; Whiteman, Matthew

2004-01-01

Free radicals and other reactive species (RS) are thought to play an important role in many human diseases. Establishing their precise role requires the ability to measure them and the oxidative damage that they cause. This article first reviews what is meant by the terms free radical, RS, antioxidant, oxidative damage and oxidative stress. It then critically examines methods used to trap RS, including spin trapping and aromatic hydroxylation, with a particular emphasis on those methods applicable to human studies. Methods used to measure oxidative damage to DNA, lipids and proteins and methods used to detect RS in cell culture, especially the various fluorescent ‘probes' of RS, are also critically reviewed. The emphasis throughout is on the caution that is needed in applying these methods in view of possible errors and artifacts in interpreting the results. PMID:15155533

The mechanisms associated with the development of hypertension after exposure to lead, mercury species or their mixtures differs with the metal and the mixture ratio.

PubMed

Wildemann, Tanja M; Siciliano, Steven D; Weber, Lynn P

2016-01-02

Hypertension is considered to be the most important risk factor for the development of cardiovascular diseases. Beside life-style risk factors, exposure to lead and mercury species are increasingly discussed as potential risk factors. Although there are a few previous studies, the underlying mechanism by which exposure to lead and mercury disturb blood pressure regulation is not currently understood. Potential mechanisms are oxidative stress production, kidney damage and activation of the renin-angiotensin system (RAS), all of which can interact to cause dysregulation of blood pressure. Male rats (Wistar) were exposed to lead, inorganic mercury, methylmercury or two mixtures of all three metals for four weeks through the drinking water. The two mixture ratios were based on ratios of known reference values or environmental exposure from the literature. To investigate the potential mechanism of actions, blood pressure was measured after four weeks and compared to plasma nitrotyrosine or reduced/oxidized glutathione levels in liver as markers for oxidative stress. Plasma renin and angiotensin II levels were used as markers for RAS activation. Finally, kidney function and injury were assessed via urinary and plasma creatinine levels, creatinine clearance and urinary kidney-injury molecule (KIM-1). While exposure to lead by itself increased oxidative stress and kidney damage along with blood pressure, inorganic mercury did not affect blood pressure or any end-point examined. Conversely, methylmercury instead increased RAS activation along with blood pressure. Surprisingly, when administered as mixtures, lead no longer increased oxidative stress or altered kidney function. Moreover, the mixture based on an environmental ratio no longer had an effect on blood pressure, while the reference value ratio still retained an increase in blood pressure. Based on our results, the prominent mechanism of action associated with the development of hypertension seems to be oxidative stress and kidney damage for lead, while increased RAS activation links methylmercury to hypertension, but these mechanisms along with hypertension disappear when metals are present in some mixtures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Modeling Strength Degradation of Fiber-Reinforced Ceramic-Matrix Composites Subjected to Cyclic Loading at Elevated Temperatures in Oxidative Environments

NASA Astrophysics Data System (ADS)

Longbiao, Li

2018-02-01

In this paper, the strength degradation of non-oxide and oxide/oxide fiber-reinforced ceramic-matrix composites (CMCs) subjected to cyclic loading at elevated temperatures in oxidative environments has been investigated. Considering damage mechanisms of matrix cracking, interface debonding, interface wear, interface oxidation and fibers fracture, the composite residual strength model has been established by combining the micro stress field of the damaged composites, the damage models, and the fracture criterion. The relationships between the composite residual strength, fatigue peak stress, interface debonding, fibers failure and cycle number have been established. The effects of peak stress level, initial and steady-state interface shear stress, fiber Weibull modulus and fiber strength, and testing temperature on the degradation of composite strength and fibers failure have been investigated. The evolution of residual strength versus cycle number curves of non-oxide and oxide/oxide CMCs under cyclic loading at elevated temperatures in oxidative environments have been predicted.

Expression of the Laccase Gene from a White Rot Fungus in Pichia pastoris Can Enhance the Resistance of This Yeast to H2O2-Mediated Oxidative Stress by Stimulating the Glutathione-Based Antioxidative System

PubMed Central

Fan, Fangfang; Zhuo, Rui; Ma, Fuying; Gong, Yangmin; Wan, Xia; Jiang, Mulan

2012-01-01

Laccase is a copper-containing polyphenol oxidase that has great potential in industrial and biotechnological applications. Previous research has suggested that fungal laccase may be involved in the defense against oxidative stress, but there is little direct evidence supporting this hypothesis, and the mechanism by which laccase protects cells from oxidative stress also remains unclear. Here, we report that the expression of the laccase gene from white rot fungus in Pichia pastoris can significantly enhance the resistance of yeast to H2O2-mediated oxidative stress. The expression of laccase in yeast was found to confer a strong ability to scavenge intracellular H2O2 and to protect cells from lipid oxidative damage. The mechanism by which laccase gene expression increases resistance to oxidative stress was then investigated further. We found that laccase gene expression in Pichia pastoris could increase the level of glutathione-based antioxidative activity, including the intracellular glutathione levels and the enzymatic activity of glutathione peroxidase, glutathione reductase, and γ-glutamylcysteine synthetase. The transcription of the laccase gene in Pichia pastoris was found to be enhanced by the oxidative stress caused by exogenous H2O2. The stimulation of laccase gene expression in response to exogenous H2O2 stress further contributed to the transcriptional induction of the genes involved in the glutathione-dependent antioxidative system, including PpYAP1, PpGPX1, PpPMP20, PpGLR1, and PpGSH1. Taken together, these results suggest that the expression of the laccase gene in Pichia pastoris can enhance the resistance of yeast to H2O2-mediated oxidative stress by stimulating the glutathione-based antioxidative system to protect the cell from oxidative damage. PMID:22706050

Chromosome and oxidative damage biomarkers in lymphocytes of Parkinson's disease patients.

PubMed

Migliore, L; Scarpato, R; Coppede, F; Petrozzi, L; Bonuccelli, U; Rodilla, V

2001-10-01

As cancer development usually results from exposure to several environmental risk factors in interaction with the genetic susceptibility of the host, it could be of interest to investigate if neurodegeneration, as occurs in Parkinson's disease (PD) patients can be attributed at least partially, to environmental risk factors. There is growing evidence that oxidative stress could play a significant role as a risk factor in the aetiology and pathogenesis of neurodegenerative diseases, emphasising the need for new individual and human-based approaches. The aim of our research is to explore the relation between chromosome instability and oxidative stress biomarkers in Parkinson's disease using a variety of strategies. We determined peripheral markers for oxidative damage in PD by testing for spontaneous and induced chromosomal damage, DNA strand breaks, oxidised pyrimidines and altered purines both in peripheral blood and cultured lymphocytes. We also measured glutathione S-transferase activity in the plasma of patients and controls. Compared to healthy controls, PD patients show higher frequencies of micronuclei (17.2 +/- 4.8 vs. 9.0 +/- 3.4, p < 0.001) and a significant increase in the levels of single strand breaks (SSB). Significant differences were also obtained in the distribution of oxidised purine bases between the two groups. Preliminary data obtained by fluorescence in situ hybridization analysis showed that the percentage of centromere negative micronuclei is higher than that of centromere positive micronuclei. Glutathione S-transferase activity in plasma from PD patients and controls was also measured and the enzymatic activity in PD patients was lower than in healthy controls.

Damage and recovery of skin barrier function after glycolic acid chemical peeling and crystal microdermabrasion.

PubMed

Song, Ji Youn; Kang, Hyun A; Kim, Mi-Yeon; Park, Young Min; Kim, Hyung Ok

2004-03-01

Superficial chemical peeling and microdermabrasion have become increasingly popular methods for producing facial rejuvenation. However, there are few studies reporting the skin barrier function changes after these procedures. To evaluate objectively the degree of damage visually and the time needed for the skin barrier function to recover after glycolic acid peeling and aluminum oxide crystal microdermabrasion using noninvasive bioengineering methods. Superficial chemical peeling using 30%, 50%, and 70% glycolic acid and aluminum oxide crystal microdermabrasion were used on the volar forearm of 13 healthy women. The skin response was measured by a visual observation and using an evaporimeter, corneometer, and colorimeter before and after peeling at set time intervals. Both glycolic acid peeling and aluminum oxide crystal microdermabrasion induced significant damage to the skin barrier function immediately after the procedure, and the degree of damage was less severe after the aluminum oxide crystal microdermabrasion compared with glycolic acid peeling. The damaged skin barrier function had recovered within 24 hours after both procedures. The degree of erythema induction was less severe after the aluminum oxide crystal microdermabrasion compared with the glycolic acid peeling procedure. The degree of erythema induced after the glycolic acid peeling procedure was not proportional to the peeling solution concentration used. The erythema subsided within 1 day after the aluminum oxide crystal microdermabrasion procedure and within 4 days after the glycolic acid peeling procedure. These results suggest that the skin barrier function is damaged after the glycolic acid peeling and aluminum oxide crystal microdermabrasion procedure but recovers within 1 to 4 days. Therefore, repeating the superficial peeling procedure at 2-week intervals will allow sufficient time for the damaged skin to recover its barrier function.

Surface modification of Cu metal particles by the chemical reaction between the surface oxide layer and a halogen surfactant

NASA Astrophysics Data System (ADS)

Yokoyama, Shun; Takahashi, Hideyuki; Itoh, Takashi; Motomiya, Kenichi; Tohji, Kazuyuki

2014-01-01

Surface oxides on small (2-5 μm) copper metal particles can be removed by chemical reaction with tris(2,3-dibromopropyl) isocyanurate (TIC) in diethylene glycol mono-n-hexyl ether (DGHE) solution under mild conditions where metal particles are not damaged. Surface oxides convert to copper bromide species and subsequently dissolve into the solvent. It was found that resultant surface species are resistant to re-oxidation due to remaining surface bromides. This finding opens up a possibility to create microclines based on cheap copper nanoparticles.

Synergistic erosion/corrosion of superalloys in PFB coal combustor effluent

NASA Technical Reports Server (NTRS)

Benford, S. M.; Zellars, G. R.; Lowell, C. E.

1981-01-01

Two Ni-based superalloys were exposed to the high velocity effluent of a pressurized fluidized bed coal combustor. Targets were 15 cm diameter rotors operating at 40,000 rpm and small flat plate specimens. Above an erosion rate threshold, the targets were eroded to bare metal. The presence of accelerated oxidation at lower erosion rates suggests erosion/corrosion synergism. Various mechanisms which may contribute to the observed oxide growth enhancement include erosive removal of protective oxide layers, oxide and subsurface cracking, and chemical interaction with sulfur in the gas and deposits through damaged surface layers.

Electro-purification of carbon nanotube networks without damaging the assembly structure and crystallinity

NASA Astrophysics Data System (ADS)

Yang, Xueqin; Yang, Ming; Zhang, Huichao; Zhao, Jingna; Zhang, Xiaohua; Li, Qingwen

2018-06-01

Fe-containing nanoparticles are of a high mass fraction in the as-grown carbon nanotube (CNT) network. By controlling the S-to-Fe atom ratio in the growth feedstock and introducing water as a weak oxidant, highly crystalline few-walled CNT network can be obtained, with a mass fraction of over 20 wt% for the Fe-containing nanoparticles. We report here an electron-oxidation-based purification method to efficiently remove the Fe-containing nanoparticles without inducing clear damage to either the assembly structure or the tube crystallinity. The purification could increase the ratio between Raman D and G peak intensities slightly from 0.08 to 0.12, decrease the specific conductivity from 0.31 to 0.24 S m2/g and the Fe content from >20 wt% to ≈1 wt%, and modify the capacitance just by about 13 F/g. All these indicate that the CNT network was well maintained by such gentle electro-oxidation-based purification. In addition, the purified CNT network can exhibit advantages in mechanical and electrical applications.

Mobile phone radiation-induced free radical damage in the liver is inhibited by the antioxidants N-acetyl cysteine and epigallocatechin-gallate.

PubMed

Ozgur, Elcin; Güler, Göknur; Seyhan, Nesrin

2010-11-01

To investigate oxidative damage and antioxidant enzyme status in the liver of guinea pigs exposed to mobile phone-like radiofrequency radiation (RFR) and the potential protective effects of N-acetyl cysteine (NAC) and epigallocatechin-gallate (EGCG) on the oxidative damage. Nine groups of guinea pigs were used to study the effects of exposure to an 1800-MHz Global System for Mobile Communications (GSM)-modulated signal (average whole body Specific Absorption Rate (SAR) of 0.38 W/kg, 10 or 20 min per day for seven days) and treatment with antioxidants. Significant increases in malondialdehyde (MDA) and total nitric oxide (NO(x)) levels and decreases in activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and glutathione peroxidase (GSH-Px) were observed in the liver of guinea pigs after RFR exposure. Only NAC treatment induces increase in hepatic GSH-Px activities, whereas EGCG treatment alone attenuated MDA level. Extent of oxidative damage was found to be proportional to the duration of exposure (P < 0.05). Mobile phone-like radiation induces oxidative damage and changes the activities of antioxidant enzymes in the liver. The adverse effect of RFR may be related to the duration of mobile phone use. NAC and EGCG protect the liver tissue against the RFR-induced oxidative damage and enhance antioxidant enzyme activities.

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

PubMed Central

Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

Allelochemical Stress Can Trigger Oxidative Damage in Receptor Plants

PubMed Central

Lara-Núñez, Aurora; Anaya, Ana Luisa

2007-01-01

Plants can interact with other plants through the release of chemical compounds or allelochemicals. These compounds released by donor plants influence germination, growth, development, and establishment of receptor plants; having an important role on the pattern of vegetation, i.e as invasive strategy, and on crop productivity. This phytotoxic or negative effect of the released allelochemicals (allelochemical stress) is caused by modifying or altering diverse metabolic processes, having many molecular targets in the receptor plants. Recently, using an aggressive and allelopathic plant Sicyos deppei as the donor plant, and Lycopersicon esculentum as the receptor plant, we showed that the allelochemicals released by S. deppei caused oxidative damage through an increase in reactive oxygen species (ROS) and activation or modification of antioxidant enzymes. Based on this study, we proposed that oxidative stress is one of the mechanisms, among others, by which an allelopathic plant causes phytotoxicity to other plants. PMID:19704677

Apollo 16 Mission Anomaly Report No. 1: Oxidizer Deservicing Tank Failure

NASA Technical Reports Server (NTRS)

1972-01-01

The command module reaction control system is emptied of all remaining propellant using ground support equipment designed to provide an acid/base neutralization of the propellant in both the liquid and gaseous phases so that it may be disposed of safely. During the deactivation operation of the oxidizer from the Apollo 16 command module on 7 May 1972, the scrubber tank of the decontamination unit exploded, destroying the ground support equipment unit and damaging the building that housed the operation. Only minor injuries were received by the personnel in the area and the command module was not damaged. Test results show that the failure was caused by an insufficient quantity of neutralizer for the quantity of oxidizer. This insufficiency lead to exothermic nitration-type reactions which produced large quantities of gas at a very high rate and failed the decontamination tank.

Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages

PubMed Central

Deng, Song-Yun; Zhang, Le-Meng; Ai, Yu-hang; Pan, Pin-Hua; Zhao, Shuang-Ping; Su, Xiao-Li; Wu, Dong-Dong; Tan, Hong-Yi; Zhang, Li-Na; Tsung, Allan

2017-01-01

Sepsis causes many early deaths; both macrophage mitochondrial damage and oxidative stress responses are key factors in its pathogenesis. Although the exact mechanisms responsible for sepsis-induced mitochondrial damage are unknown, the nuclear transcription factor, interferon regulatory factor-1 (IRF-1) has been reported to cause mitochondrial damage in several diseases. Previously, we reported that in addition to promoting systemic inflammation, IRF-1 promoted the apoptosis of and inhibited autophagy in macrophages. In the present study, we hypothesized that lipopolysaccharide (LPS)-induced IRF-1 activation in macrophages may promote mitochondrial damage and oxidative stress. In vitro, LPS was found to promote IRF-1 activation, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, superoxide dismutase (SOD) consumption, malondialdehyde (MDA) accumulation and mitochondrial depolarization in macrophages in a time- and dose-dependent manner. These effects were abrogated in cells in which IRF-1 was knocked down. Furthermore, IRF-1 overexpression increased LPS-induced oxidative stress responses and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 knockout (KO) mice produced less ROS and had less mitochondrial depolarization and damage following the administration of LPS, when compared to their wild-type (WT) counterparts. In addition, IRF-1 KO mice exhibited a decreased release of mitochondrial DNA (mtDNA) following the administration of LPS. Thus, IRF-1 may be a critical factor in augmenting LPS-induced oxidative stress and mitochondrial damage in macrophages. PMID:28849179

Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents

PubMed Central

Ma, Yingxin; Nie, Hui; Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Shao, Jiaxiang; He, Xin; Zhang, Tingting; Zheng, Chaobo; Xia, Weiliang; Ying, Weihai

2012-01-01

Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX – a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation. PMID:22837810

Preterm newborns show slower repair of oxidative damage and paternal smoking associated DNA damage.

PubMed

Vande Loock, Kim; Ciardelli, Roberta; Decordier, Ilse; Plas, Gina; Haumont, Dominique; Kirsch-Volders, Micheline

2012-09-01

Newborns have to cope with hypoxia during delivery and a sudden increase in oxygen at birth. Oxygen will partly be released as reactive oxygen species having the potential to cause damage to DNA and proteins. In utero, increase of most (non)-enzymatic antioxidants occurs during last weeks of gestation, making preterm neonates probably more sensitive to oxidative stress. Moreover, it has been hypothesized that oxidative stress might be the common etiological factor for certain neonatal diseases in preterm infants. The aim of this study was to assess background DNA damage; in vitro H(2)O(2) induced oxidative DNA damage and repair capacity (residual DNA damage) in peripheral blood mononucleated cells from 25 preterm newborns and their mothers. In addition, demographic data were taken into account and repair capacity of preterm was compared with full-term newborns. Multivariate linear regression analysis revealed that preterm infants from smoking fathers have higher background DNA damage levels than those from non-smoking fathers, emphasizing the risk of paternal smoking behaviour for the progeny. Significantly higher residual DNA damage found after 15-min repair in preterm children compared to their mothers and higher residual DNA damage after 2 h compared to full-term newborns suggest a slower DNA repair capacity in preterm children. In comparison with preterm infants born by caesarean delivery, preterm infants born by vaginal delivery do repair more slowly the in vitro induced oxidative DNA damage. Final impact of passive smoking and of the slower DNA repair activity of preterm infants need to be confirmed in a larger study population combining transgenerational genetic and/or epigenetic effects, antioxidant levels, genotypes, repair enzyme efficiency/levels and infant morbidity.

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

PubMed

Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

2017-04-01

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

Reproductive Benefit of Oxidative Damage: An Oxidative Stress “Malevolence”?

PubMed Central

Poljsak, B.; Milisav, I.; Lampe, T.; Ostan, I.

2011-01-01

High levels of reactive oxygen species (ROS) compared to antioxidant defenses are considered to play a major role in diverse chronic age-related diseases and aging. Here we present an attempt to synthesize information about proximate oxidative processes in aging (relevant to free radical or oxidative damage hypotheses of aging) with an evolutionary scenario (credited here to Dawkins hypotheses) involving tradeoffs between the costs and benefits of oxidative stress to reproducing organisms. Oxidative stress may be considered a biological imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to environment was applied to the role of oxidative stress in processes like famine and infectious diseases and their consequences at the molecular level such as mutations and cell signaling. Arguments are presented that oxidative damage is not necessarily an evolutionary mistake but may be beneficial for reproduction; this may prevail over its harmfulness to health and longevity in evolution. Thus, Dawkins' principle of biological “malevolence” may be an additional biological paradigm for explaining the consequences of oxidative stress. PMID:21969876

The role of the iron catalyst in the toxicity of multi-walled carbon nanotubes (MWCNTs).

PubMed

Visalli, Giuseppa; Facciolà, Alessio; Iannazzo, Daniela; Piperno, Anna; Pistone, Alessandro; Di Pietro, Angela

2017-09-01

This study aimed to investigate the role of iron, used as a catalyst, in the biological response to pristine and functionalized multi-walled carbon nanotubes (p/fMWCNTs) with an iron content of 2.5-2.8%. Preliminarily, we assessed the pro-oxidant activity of MWCNTs-associated iron by an abiotic test. To evaluate iron bioavailability, we measured intracellular redox-active iron in A549 cells exposed to both MWCNT suspensions and to the cell medium preconditioned by MWCNTs, in order to assess the iron dissolution rate under physiological conditions. Moreover, in exposed cells, we detected ROS levels, 8-oxo-dG and mitochondrial function. The results clearly highlighted that MWCNTs- associated iron was not redox-active and that iron leakage did not occur under physiological conditions, including the oxidative burst of specialized cells. Despite this, in MWCNTs exposed cells, higher level of intracellular redox-active iron was measured in comparison to control and a significant time-dependent ROS increase was observed (P<0.01). Higher levels of 8-oxo-dG, a marker of oxidative DNA damage, and decreased mitochondrial function, confirmed the oxidative stress induced by MWCNTs. Based on the results we believe that oxidative damage could be attributable to the release of endogenous redox-active iron. This was due to the damage of acidic vacuolar compartment caused by endocytosis-mediated MWCNT internalization. Copyright © 2017 Elsevier GmbH. All rights reserved.

The role of operating parameters and oxidative damage mechanisms of advanced chemical oxidation processes in the combat against antibiotic-resistant bacteria and resistance genes present in urban wastewater.

PubMed

Michael-Kordatou, I; Karaolia, P; Fatta-Kassinos, D

2018-02-01

An upsurge in the study of antibiotic resistance in the environment has been observed in the last decade. Nowadays, it is becoming increasingly clear that urban wastewater is a key source of antibiotic resistance determinants, i.e. antibiotic-resistant bacteria and antibiotic resistance genes (ARB&ARGs). Urban wastewater reuse has arisen as an important component of water resources management in the European Union and worldwide to address prolonged water scarcity issues. Especially, biological wastewater treatment processes (i.e. conventional activated sludge), which are widely applied in urban wastewater treatment plants, have been shown to provide an ideal environment for the evolution and spread of antibiotic resistance. The ability of advanced chemical oxidation processes (AOPs), e.g. light-driven oxidation in the presence of H 2 O 2 , ozonation, homogeneous and heterogeneous photocatalysis, to inactivate ARB and remove ARGs in wastewater effluents has not been yet evaluated through a systematic and integrated approach. Consequently, this review seeks to provide an extensive and critical appraisal on the assessment of the efficiency of these processes in inactivating ARB and removing ARGs in wastewater effluents, based on recent available scientific literature. It tries to elucidate how the key operating conditions may affect the process efficiency, while pinpointing potential areas for further research and major knowledge gaps which need to be addressed. Also, this review aims at shedding light on the main oxidative damage pathways involved in the inactivation of ARB and removal of ARGs by these processes. In general, the lack and/or heterogeneity of the available scientific data, as well as the different methodological approaches applied in the various studies, make difficult the accurate evaluation of the efficiency of the processes applied. Besides the operating conditions, the variable behavior observed by the various examined genetic constituents of the microbial community, may be directed by the process distinct oxidative damage mechanisms in place during the application of each treatment technology. For example, it was shown in various studies that the majority of cellular damage by advanced chemical oxidation may be on cell wall and membrane structures of the targeted bacteria, leaving the internal components of the cells relatively intact/able to repair damage. As a result, further in-depth mechanistic studies are required, to establish the optimum operating conditions under which oxidative mechanisms target internal cell components such as genetic material and ribosomal structures more intensively, thus conferring permanent damage and/or death and preventing potential post-treatment re-growth. Copyright © 2017 Elsevier Ltd. All rights reserved.

SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

PubMed Central

Cao, Guo-fan; Cao, Cong; Jiang, Qin

2016-01-01

Excessive Ultra-violet (UV) radiation causes oxidative damages and apoptosis in retinal pigment epithelium (RPE) cells. Here we tested the potential activity of SC79, a novel small molecule activator of Akt, against the process. We showed that SC79 activated Akt in primary and established (ARPE-19 line) RPE cells. It protected RPE cells from UV damages possibly via inhibiting cell apoptosis. Akt inhibition, via an Akt specific inhibitor (MK-2206) or Akt1 shRNA silence, almost abolished SC79-induced RPE cytoprotection. Further studies showed that SC79 activated Akt-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited UV-induced oxidative stress in RPE cells. Reversely, Nrf2 shRNA knockdown or S40T mutation attenuated SC79-induced anti-UV activity. For the in vivo studies, we showed that intravitreal injection of SC79 significantly protected mouse retina from light damages. Based on these results, we suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis. PMID:27517753

Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ.

PubMed

Dare, Anna J; Bolton, Eleanor A; Pettigrew, Gavin J; Bradley, J Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P

2015-08-01

Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Protection against renal ischemia–reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ

PubMed Central

Dare, Anna J.; Bolton, Eleanor A.; Pettigrew, Gavin J.; Bradley, J. Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P.

2015-01-01

Ischemia–reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24 h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. PMID:25965144

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

PubMed Central

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

Magmas functions as a ROS regulator and provides cytoprotection against oxidative stress-mediated damages

PubMed Central

Srivastava, S; Sinha, D; Saha, P P; Marthala, H; D'Silva, P

2014-01-01

Redox imbalance generates multiple cellular damages leading to oxidative stress-mediated pathological conditions such as neurodegenerative diseases and cancer progression. Therefore, maintenance of reactive oxygen species (ROS) homeostasis is most important that involves well-defined antioxidant machinery. In the present study, we have identified for the first time a component of mammalian protein translocation machinery Magmas to perform a critical ROS regulatory function. Magmas overexpression has been reported in highly metabolically active tissues and cancer cells that are prone to oxidative damage. We found that Magmas regulates cellular ROS levels by controlling its production as well as scavenging. Magmas promotes cellular tolerance toward oxidative stress by enhancing antioxidant enzyme activity, thus preventing induction of apoptosis and damage to cellular components. Magmas enhances the activity of electron transport chain (ETC) complexes, causing reduced ROS production. Our results suggest that J-like domain of Magmas is essential for maintenance of redox balance. The function of Magmas as a ROS sensor was found to be independent of its role in protein import. The unique ROS modulatory role of Magmas is highlighted by its ability to increase cell tolerance to oxidative stress even in yeast model organism. The cytoprotective capability of Magmas against oxidative damage makes it an important candidate for future investigation in therapeutics of oxidative stress-related diseases. PMID:25165880

The Levels of Cortisol, Oxidative Stress, and DNA Damage in the Victims of Childhood Sexual Abuse: A Preliminary Study.

PubMed

Şimşek, Şeref; Kaplan, İbrahim; Uysal, Cem; Yüksel, Tuğba; Alaca, Rümeysa

2016-01-01

In this study we aimed to investigate serum cortisol, oxidative stress, and DNA damage in children who are sexual abuse victims. The study included 38 children who sustained child sexual abuse and 38 age- and gender-matched children who did not have a history of trauma. Cortisol levels reflecting the status of the hypothalamic-pituitary-adrenal axis, anti-oxidant enzymes glutathione peroxidase, superoxide dismutase, natural anti-oxidant coenzyme Q, and 8-hydroxy-2-deoxyguanosine as the indicator of DNA damage were analyzed in serum samples using the enzyme linked immunosorbent assay method. Cortisol levels were significantly higher in the child sexual abuse group compared to the control group. There were no significant differences between the groups in terms of oxidative stress and DNA damage. Cortisol and 8-hydroxy-2-deoxyguanosine levels decreased as the time elapsed since the sexual abuse increased. Coenzyme Q level was lower in victims who sustained multiple assaults than in the victims of a single assault. Cortisol and superoxide dismutase levels were lower in the victims of familial sexual abuse. Decreases in cortisol and 8-hydroxy-2-deoxyguanosine levels as time elapsed may be an adaptation to the toxic effects of high cortisol levels over a prolonged period of time. Child sexual abuse did not result in oxidative stress and DNA damage; however, some features of sexual abuse raised the level of oxidative stress.

In vivo reduction of erythrocyte oxidant stress in a murine model of beta-thalassemia.

PubMed

de Franceschi, Lucia; Turrini, Franco; Honczarenko, Marek; Ayi, Kojio; Rivera, Alicia; Fleming, Mark D; Law, Terry; Mannu, Franca; Kuypers, Frans A; Bast, Aalt; van der Vijgh, Wim J F; Brugnara, Carlo

2004-11-01

Oxidant damage is an important contributor to the premature destruction of erythrocytes and anemia in thalassemias. To assess the extent of oxidant damage of circulating erythrocytes and the effects of antioxidant therapy on erythrocyte characteristics and anemia, we used a mouse model of human beta-thalassemia intermedia (b1/b2 deletion). Several parameters indicative of oxidant damage were measured at baseline and following administration of the semi-synthetic flavonoid antioxidant, 7-monohydroxyethylrutoside (monoHER), to beta-thalassemic mice at a dose of either 500 mg/kg i.p. once a day (n=6) or 250 mg/kg i.p. twice a day (n=6) for 21 days. Significant erythrocyte oxidant damage at baseline was indicated by: (i) dehydration, reduced cell K content, and up-regulated K-Cl co-transport; (ii) marked membrane externalization of phosphatidylserine; (iii) reduced plasma and membrane content of vitamin E; and (iv) increased membrane bound IgG. MonoHER treatment increased erythrocyte K content, and markedly improved all cellular indicators of oxidant stress and of lipid membrane peroxidation. While anemia did not improve, monoHER therapy reduced reticulocyte counts, improved survival of a fraction of red cells, and reduced ineffective erythropoiesis with decreased total bilirubin, lactate dehydrogenase and plasma iron. Antioxidant therapy reverses several indicators of oxidant damage in vivo. These promising antioxidant effects of monoHER should be investigated further.

Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants

PubMed Central

Poljsak, Borut; Šuput, Dušan; Milisav, Irina

2013-01-01

Free radical damage is linked to formation of many degenerative diseases, including cancer, cardiovascular disease, cataracts, and aging. Excessive reactive oxygen species (ROS) formation can induce oxidative stress, leading to cell damage that can culminate in cell death. Therefore, cells have antioxidant networks to scavenge excessively produced ROS. The balance between the production and scavenging of ROS leads to homeostasis in general; however, the balance is somehow shifted towards the formation of free radicals, which results in accumulated cell damage in time. Antioxidants can attenuate the damaging effects of ROS in vitro and delay many events that contribute to cellular aging. The use of multivitamin/mineral supplements (MVMs) has grown rapidly over the past decades. Some recent studies demonstrated no effect of antioxidant therapy; sometimes the intake of antioxidants even increased mortality. Oxidative stress is damaging and beneficial for the organism, as some ROS are signaling molecules in cellular signaling pathways. Lowering the levels of oxidative stress by antioxidant supplements is not beneficial in such cases. The balance between ROS and antioxidants is optimal, as both extremes, oxidative and antioxidative stress, are damaging. Therefore, there is a need for accurate determination of individual's oxidative stress levels before prescribing the supplement antioxidants. PMID:23738047

ATM directs DNA damage responses and proteostasis via genetically separable pathways.

PubMed

Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

2018-01-09

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease

PubMed Central

Sung, Chih-Chien; Hsu, Yu-Chuan; Lin, Yuh-Feng

2013-01-01

Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS) production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate), deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies. PMID:24058721

A Meta-Analysis Of Corrosion Studies for Maritime Patrol and Reconnaissance Aircraft (MPRA)

DTIC Science & Technology

2016-09-01

performed onsite. Aircraft rating was based upon the presence and/or extent of paint adhesion, paint cracking , clean ability, fluid damage, oxidation...because of corrosion control maintenance. No significant issues were observed related to paint cracking , fluid damage, corrosion, and clean ability of...HEXAMETHYLENEDIISOCYANATE 822-06-0 83194 X-310A; POLYURETHANE CATALYST XYLENE 1330-20-7 82649 X-530; HS EPOXY ENAMEL CURING SOLUTION BUTANOL 71-36-3

Evaluation of Oxidation Damage in Thermal Barrier Coating Systems

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Miller, Robert A.

1996-01-01

A method based on the technique of dilatometry has been established to quantitatively evaluate the interfacial damage due to the oxidation in a thermal barrier coating system. Strain isolation and adhesion coefficients have been proposed to characterize the thermal barrier coating (TBC) performance based on its thermal expansion behavior. It has been found that, for a thermal barrier coating system consisting of ZrO2-8%Y2O3/FeCrAlY/4140 steel substrate, the oxidation of the bond coat and substrate significantly reduced the ceramic coating adherence, as inferred from the dilatometry measurements. The in-situ thermal expansion measurements under 30 deg C to 700 deg C thermal cycling in air showed that the adhesion coefficient, A(sub i) decreased by 25% during the first 35 oxidation cycles. Metallography showed that delamination occurred at both the ceramic/bond coat and bond coat/substrate interfaces. In addition, the strain isolation effect has been improved by increasing the FeCrAlY bond coat thickness. The strain isolation coefficient, Si, increased from about 0.04 to 0.25, as the bond coat thickness changed from 0.1 mm to 1.0 mm. It may be possible to design optimum values of strain isolation and interface adhesion coefficients to achieve the best TBC performance.

Concerted action of Nrf2-ARE pathway, MRN complex, HMGB1 and inflammatory cytokines - Implication in modification of radiation damage

PubMed Central

Anuranjani; Bala, Madhu

2014-01-01

Whole body exposure to low linear energy transfer (LET) ionizing radiations (IRs) damages vital intracellular bio-molecules leading to multiple cellular and tissue injuries as well as pathophysiologies such as inflammation, immunosuppression etc. Nearly 70% of damage is caused indirectly by radiolysis of intracellular water leading to formation of reactive oxygen species (ROS) and free radicals and producing a state of oxidative stress. The damage is also caused by direct ionization of biomolecules. The type of radiation injuries is dependent on the absorbed radiation dose. Sub-lethal IR dose produces more of DNA base damages, whereas higher doses produce more DNA single strand break (SSBs), and double strand breaks (DSBs). The Nrf2-ARE pathway is an important oxidative stress regulating pathway. The DNA DSBs repair regulated by MRN complex, immunomodulation and inflammation regulated by HMGB1 and various types of cytokines are some of the key pathways which interact with each other in a complex manner and modify the radiation response. Because the majority of radiation damage is via oxidative stress, it is essential to gain in depth understanding of the mechanisms of Nrf2-ARE pathway and understand its interactions with MRN complex, HMGB1 and cytokines to increase our understanding on the radiation responses. Such information is of tremendous help in development of medical radiation countermeasures, radioprotective drugs and therapeutics. Till date no approved and safe countermeasure is available for human use. This study reviews the Nrf2-ARE pathway and its crosstalk with MRN-complex, HMGB1 and cytokines (TNF-a, IL-6, IFN-? etc.). An attempt is also made to review the modification of some of these pathways in presence of selected antioxidant radioprotective compounds or herbal extracts. PMID:25009785

Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation

PubMed Central

di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X.; Villoslada, Pablo

2013-01-01

Background Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines. This model may both facilitate understanding of the events involved in neuroinflammation and aid in the development of neuroprotective therapies for the treatment of MS and other neurodegenerative diseases. PMID:23431360

[Effect of a hypocaloric diet in the oxidative stress in obese subjects without prescription of exercise and antioxidants].

PubMed

Gutiérrez, Liliana; García, José R; Rincón, María de Jesús; Ceballos, Guillermo M; Olivares, Ivonne M

2015-07-06

Obesity is characterized by a generalized increase of adipose tissue, high production of adipocytokines and presence of oxidative systemic stress. The objective of this study was to evaluate the changes generated in the oxidative stress and anthropometric parameters in obese subjects by the prescription of a hypocaloric diet in combination with moderate aerobic exercise and supplementation with antioxidants. Oxidative damage was determined in the plasma from 30 normal weight and 30 obese subjects. Three groups of treatment were established: Hypocaloric diet (HD), HD plus moderate aerobic exercise (HDE) and HDE plus antioxidants (DHEA). Biomarkers of oxidative stress (thiobarbituric acid reactive substances [TBARS], carbonyl groups, dityrosine) and anthropometric parameters were determined. Higher values of biomarkers of oxidative damage were observed in obese (TBARS 13.74 ± 1.2 μM; carbonyl groups 0.89 ± 0.04 nmol of osazone/mg of protein; dityrosine 478.9 ± 27.4 RFU/mg of protein) in comparison to normal weight subjects (TBARS 7.08 ± 0.8 μM; carbonyl groups 0.65 ± 0.04 nmol of osazone/mg of protein; dityrosine 126.3 ± 12.6 RFU/mg of protein), thus showing the presence of an oxidative damage. The prescription of HD decreased the oxidative damage and anthropometric parameters in the obese subjects. We did not observe additional benefit effects on these determinations with HDE or HDEA treatments. We demonstrated that an HD decreases the oxidative damage in obese subjects. Oxidative stress is an important factor in the development of comorbidity in obesity. Therefore, the prescription of a HD could be a key issue in the treatment of the disease. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets.

PubMed

Vaanholt, L M; Milne, A; Zheng, Y; Hambly, C; Mitchell, S E; Valencak, T G; Allison, D B; Speakman, J R

2016-02-01

Lactation is one of the most energetically expensive behaviours, and trade-offs may exist between the energy devoted to it and somatic maintenance, including protection against oxidative damage. However, conflicting data exist for the effects of reproduction on oxidative stress. In the wild, a positive relationship is often observed, but in laboratory studies oxidative damage is often lower in lactating than in non-breeding animals. We hypothesised that this discrepancy may exist because during lactation food intake increases many-fold resulting in a large increase in the intake of dietary antioxidants which are typically high in laboratory rodent chow where they are added as a preservative. We supplied lactating and non-breeding control mice with either a standard or low antioxidant diet and studied how this affected the activity of endogenous antioxidants (catalase, superoxide dismutase; SOD, and glutathione peroxidise; GPx) and oxidative damage to proteins (protein carbonyls, PC) in liver and brain tissue. The low antioxidant diet did not significantly affect activities of antioxidant enzymes in brain or liver, and generally did not result in increased protein damage, except in livers of control mice on low antioxidant diet. Catalase activity, but not GPx or SOD, was decreased in both control and lactating mice on the low antioxidant diet. Lactating mice had significantly reduced oxidative damage to both liver and brain compared to control mice, independent of the diet they were given. In conclusion, antioxidant content of the diet did not affect oxidative stress in control or reproductive mice, and cannot explain the previously observed reduction in oxidative stress in lactating mammals studied in the laboratory. The reduced oxidative stress in the livers of lactating mice even under low antioxidant diet treatment was consistent with the 'shielding' hypothesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism.

PubMed

Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

2016-06-01

The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2 (-) scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays. Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2(-) scavenging, DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3',4'-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form.

NECTARINE PROMOTES LONGEVITY IN DROSOPHILA MELANOGASTER

PubMed Central

Boyd, Olga; Weng, Peter; Sun, Xiaoping; Alberico, Thomas; Laslo, Mara; Obenland, David M.; Kern, Bradley; Zou, Sige

2011-01-01

Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and healthspan. However, few fruits are known to improve the survival and healthspan in animals, let alone the underlying mechanisms. Here we investigate the effect of nectarine, a globally consumed fruit, on lifespan and healthspan in Drosophila melanogaster. Wild-type flies were fed the standard, dietary restriction (DR) or high fat diets supplemented with 0–4% nectarine extract. We measured lifespan, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-Hydroxynonenal-protein adduct in these flies. We also measured lifespan, locomotor activity and oxidative damage of sod1 mutant flies on the standard diet supplemented with 0–4% nectarine. Supplementation of 4% nectarine extended lifespan, increased fecundity and decreased expression of some metabolic genes, including a key gluconeogenesis gene PEPCK, and oxidative stress response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR or high fat diet. Nectarine reduced oxidative damage in wild-type females fed the high fat diet. Moreover, nectarine improved the survival and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and healthspan partly through modulating glucose metabolism and reducing oxidative damage. PMID:21406223

The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells.

PubMed

Lowes, Damon A; Wallace, Carol; Murphy, Michael P; Webster, Nigel R; Galley, Helen F

2009-04-01

Tendinitis and tendon rupture during treatment with fluoroquinolone antibiotics is thought to be mediated via oxidative stress. This study investigated whether ciprofloxacin and moxifloxacin cause oxidative stress and mitochondrial damage in cultured normal human Achilles' tendon cells and whether an antioxidant targeted to mitochondria (MitoQ) would protect against such damage better than a non-mitochondria targeted antioxidant. Human tendon cells from normal Achilles' tendons were exposed to 0-0.3 mM antibiotic for 24 h and 7 days in the presence of 1 microM MitoQ or an untargeted form, idebenone. Both moxifloxacin and ciprofloxacin resulted in up to a 3-fold increase in the rate of oxidation of dichlorodihydrofluorescein, a marker of general oxidative stress in tenocytes (p<0.0001) and loss of mitochondrial membrane permeability (p<0.001). In cells treated with MitoQ the oxidative stress was less and mitochondrial membrane potential was maintained. Mitochondrial damage to tenocytes during fluoroquinolone treatment may be involved in tendinitis and tendon rupture.

Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, enhances lipid peroxidation-mediated oxidative damage in U937 cells.

PubMed

Yang, Joon-Hyuck; Park, Jeen-Woo

2003-08-01

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Cytosolic NADP+-dependent isocitrate dehydrogenase (ICDH) in U937 cells produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of ICDH against lipid peroxidation-mediated oxidative damage in U937 cells was investigated in control cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the viability was lower and the protein oxidation, lipid peroxidation, and oxidative DNA damage, reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in oxalomalate-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin, as well as the significant decrease in the intracellular GSH level in oxalomalate-treated U937 cells upon exposure to AAPH. These results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against lipid peroxidation-mediated oxidative damage through the removal of reactive oxygen species.

Glancing-angle-deposited magnesium oxide films for high-fluence applications

DOE PAGES

Oliver, J. B.; Smith, C.; Spaulding, J.; ...

2016-06-15

Here, Birefringent magnesium oxide thin films are formed by glancing angle deposition to perform as quarter-wave plates at a wavelength of 351 nm. These films are being developed to fabricate a large aperture distributed-polarization rotator for use in vacuum, with an ultimate laser-damage–threshold goal of up to 12 J/cm 2 for a 5-ns flat-in-time pulse. The laser-damage threshold, ease of deposition, and optical film properties are evaluated. While the measured large-area laser-damage threshold is limited to ~4 J/cm 2 in vacuum, initial results based on small-spot testing in air (>20 J/cm 2) suggest MgO may be suitable with further processmore » development.« less

Optical and electrical properties of indium tin oxide films near their laser damage threshold [Electrical and optical properties of indium tin oxide films under multi-pulse laser irradiation at 1064 nm

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

Yoo, Jae -Hyuck; Lange, Andrew; Bude, Jeff

In this paper, we investigated whether the optical and electrical properties of indium tin oxide (ITO) films are degraded under laser irradiation below their laser ablation threshold. While performing multi-pulse laser damage experiments on a single ITO film (4.7 ns, 1064 nm, 10 Hz), we examined the optical and electrical properties in situ. A decrease in reflectance was observed prior to laser damage initiation. However, under sub-damage threshold irradiation, conductivity and reflectance of the film were maintained without measurable degradation. This indicates that ITO films in optoelectronic devices may be operated below their lifetime laser damage threshold without noticeable performancemore » degradation.« less

Optical and electrical properties of indium tin oxide films near their laser damage threshold [Electrical and optical properties of indium tin oxide films under multi-pulse laser irradiation at 1064 nm

DOE PAGES

Yoo, Jae -Hyuck; Lange, Andrew; Bude, Jeff; ...

2017-02-10

In this paper, we investigated whether the optical and electrical properties of indium tin oxide (ITO) films are degraded under laser irradiation below their laser ablation threshold. While performing multi-pulse laser damage experiments on a single ITO film (4.7 ns, 1064 nm, 10 Hz), we examined the optical and electrical properties in situ. A decrease in reflectance was observed prior to laser damage initiation. However, under sub-damage threshold irradiation, conductivity and reflectance of the film were maintained without measurable degradation. This indicates that ITO films in optoelectronic devices may be operated below their lifetime laser damage threshold without noticeable performancemore » degradation.« less

DNA oxidative damage and life expectancy in houseflies.

PubMed Central

Agarwal, S; Sohal, R S

1994-01-01

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

Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection.

PubMed

Visalli, Giuseppa; Riso, Romana; Facciolà, Alessio; Mondello, Placido; Caruso, Carmela; Picerno, Isa; Di Pietro, Angela; Spataro, Pasquale; Bertuccio, Maria Paola

2016-02-01

The Human papillomavirus is responsible for the most common sexually transmitted infection and is also known to be an oncogenic virus that is associated with cervical, anogenital, and head-neck cancers. The present study aims to assess whether oxidative DNA damage is correlated with the grade of HPV-related lesions. Moreover, we evaluated clinical data and unhealthy lifestyles to verify their possible influence on the genesis of oxidative DNA damage in cervical cells. We quantified the amount of 8-Oxo-2'-deoxyguanosine in DNA as a biomarker of oxidative damage in women with and without HPV infection. We also correlated oxidative damage with different stages of cervical lesions and available clinical data (e.g., HPV genotypes). To identify HPV infections, in which proteins with a transforming potential are produced, we performed a qualitative detection of HPV E6/E7 mRNA. Our results showed greater oxidative damage in HPV-related dysplastic cervical lesions compared to samples with normal cytology, especially in women with high-grade squamous intraepithelial lesions. The latter showed a closed link with high-risk HPV genotypes. Reactive oxygen species can induce DNA double-strand breaks in both the host DNA and in the circular viral episome; this could facilitate the integration of the virus, promoting HPV carcinogenesis. Therefore, in HPV-infected women, it could be useful to reduce additional resources of reactive oxygen/nitrogen species (RONS) with a healthy lifestyle. © 2015 Wiley Periodicals, Inc.

Thermo-Oxidative Induced Damage in Polymer Composites: Microstructure Image-Based Multi-Scale Modeling and Experimental Validation

NASA Astrophysics Data System (ADS)

Hussein, Rafid M.; Chandrashekhara, K.

2017-11-01

A multi-scale modeling approach is presented to simulate and validate thermo-oxidation shrinkage and cracking damage of a high temperature polymer composite. The multi-scale approach investigates coupled transient diffusion-reaction and static structural at macro- to micro-scale. The micro-scale shrinkage deformation and cracking damage are simulated and validated using 2D and 3D simulations. Localized shrinkage displacement boundary conditions for the micro-scale simulations are determined from the respective meso- and macro-scale simulations, conducted for a cross-ply laminate. The meso-scale geometrical domain and the micro-scale geometry and mesh are developed using the object oriented finite element (OOF). The macro-scale shrinkage and weight loss are measured using unidirectional coupons and used to build the macro-shrinkage model. The cross-ply coupons are used to validate the macro-shrinkage model by the shrinkage profiles acquired using scanning electron images at the cracked surface. The macro-shrinkage model deformation shows a discrepancy when the micro-scale image-based cracking is computed. The local maximum shrinkage strain is assumed to be 13 times the maximum macro-shrinkage strain of 2.5 × 10-5, upon which the discrepancy is minimized. The microcrack damage of the composite is modeled using a static elastic analysis with extended finite element and cohesive surfaces by considering the modulus spatial evolution. The 3D shrinkage displacements are fed to the model using node-wise boundary/domain conditions of the respective oxidized region. Microcrack simulation results: length, meander, and opening are closely matched to the crack in the area of interest for the scanning electron images.

Prediction and measurement of radiation damage to CMOS devices on board spacecraft

NASA Technical Reports Server (NTRS)

Cliff, R. A.; Danchenko, V.; Stassinopoulos, E. G.; Sing, M.; Brucker, G. J.; Ohanian, R. S.

1976-01-01

The initial results obtained from the Complementary Metal Oxide Semiconductors Radiation Effects Measurement experiment are presented. Predictions of radiation damage to C-MOS devices are based on standard environment models and computational techniques. A comparison of the shifts in CMOS threshold potentials, that is, those measured in space to those obtained from the on the ground simulation experiment with Co 60, indicated that the measured space damage is greater than predicted by a factor of two for shields thicker than 100 mils (2.54 mm), but agrees well with predictions for the thinner shields.

Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

PubMed

Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

2017-01-01

The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

Base excision repair: a critical player in many games.

PubMed

Wallace, Susan S

2014-07-01

This perspective reviews the many dimensions of base excision repair from a 10,000 foot vantage point and provides one person's view on where the field is headed. Enzyme function is considered under the lens of X-ray diffraction and single molecule studies. Base excision repair in chromatin and telomeres, regulation of expression and the role of posttranslational modifications are also discussed in the context of enzyme activities, cellular localization and interacting partners. The specialized roles that base excision repair play in transcriptional activation by active demethylation and targeted oxidation as well as how base excision repair functions in the immune processes of somatic hypermutation and class switch recombination and its possible involvement in retroviral infection are also discussed. Finally the complexities of oxidative damage and its repair and its link to neurodegenerative disorders, as well as the role of base excision repair as a tumor suppressor are examined in the context of damage, repair and aging. By outlining the many base excision repair-related mysteries that have yet to be unraveled, hopefully this perspective will stimulate further interest in the field. Copyright © 2014 Elsevier B.V. All rights reserved.

Incision of trivalent chromium [Cr(III)]-induced DNA damage by Bacillus caldotenax UvrABC endonuclease.

PubMed

O'Brien, Travis J; Jiang, Guohui; Chun, Gina; Mandel, H George; Westphal, Craig S; Kahen, Kaveh; Montaser, Akbar; States, J Christopher; Patierno, Steven R

2006-11-07

Some hexavalent chromium [Cr(VI)]-containing compounds are lung carcinogens. Once within cells, Cr(VI) is reduced to trivalent chromium [Cr(III)] which displays an affinity for both DNA bases and the phosphate backbone. A diverse array of genetic lesions is produced by Cr including Cr-DNA monoadducts, DNA interstrand crosslinks (ICLs), DNA-Cr-protein crosslinks (DPCs), abasic sites, DNA strand breaks and oxidized bases. Despite the large amount of information available on the genotoxicity of Cr, little is known regarding the molecular mechanisms involved in the removal of these lesions from damaged DNA. Recent work indicates that nucleotide excision repair (NER) is involved in the processing of Cr-DNA adducts in human and rodent cells. In order to better understand this process at the molecular level and begin to identify the Cr-DNA adducts processed by NER, the incision of CrCl(3) [Cr(III)]-damaged plasmid DNA was studied using a thermal-resistant UvrABC NER endonuclease from Bacillus caldotenax (Bca). Treatment of plasmid DNA with Cr(III) (as CrCl(3)) increased DNA binding as a function of dose. For example, at a Cr(III) concentration of 1 microM we observed approximately 2 Cr(III)-DNA adducts per plasmid. At this same concentration of Cr(III) we found that approximately 17% of the plasmid DNA contained ICLs ( approximately 0.2 ICLs/plasmid). When plasmid DNA treated with Cr(III) (1 microM) was incubated with Bca UvrABC we observed approximately 0.8 incisions/plasmid. The formation of endonuclease IV-sensitive abasic lesions or Fpg-sensitive oxidized DNA bases was not detected suggesting that the incision of Cr(III)-damaged plasmid DNA by UvrABC was not related to the generation of oxidized DNA damage. Taken together, our data suggest that a sub-fraction of Cr(III)-DNA adducts is recognized and processed by the prokaryotic NER machinery and that ICLs are not necessarily the sole lesions generated by Cr(III) that are substrates for NER.

Effects of hydrogen-rich water on aging periodontal tissues in rats

PubMed Central

Tomofuji, Takaaki; Kawabata, Yuya; Kasuyama, Kenta; Endo, Yasumasa; Yoneda, Toshiki; Yamane, Mayu; Azuma, Tetsuji; Ekuni, Daisuke; Morita, Manabu

2014-01-01

Oxidative damage is involved in age-related inflammatory reactions. The anti-oxidative effects of hydrogen-rich water suppress oxidative damage, which may aid in inhibiting age-related inflammatory reactions. We investigated the effects of drinking hydrogen-rich water on aging periodontal tissues in healthy rats. Four-month-old male Fischer 344 rats (n = 12) were divided into two groups: the experimental group (hydrogen-rich water treatment) and the control group (distilled water treatment). The rats consumed hydrogen-rich water or distilled water until 16 months of age. The experimental group exhibited lower periodontal oxidative damage at 16 months of age than the control group. Although protein expression of interleukin-1β did not differ, gene expression of Nod-like receptor protein 3 inflammasomes was activated in periodontal tissues from the experimental group as compared with the control group. Drinking hydrogen-rich water is proposed to have anti-aging effects on periodontal oxidative damage, but not on inflammatory reactions in healthy rats. PMID:24985521

Effect of vitamin E and C supplementation on oxidative damage and total antioxidant capacity in lead-exposed workers.

PubMed

Rendón-Ramírez, Adela-Leonor; Maldonado-Vega, María; Quintanar-Escorza, Martha-Angelica; Hernández, Gerardo; Arévalo-Rivas, Bertha-Isabel; Zentella-Dehesa, Alejandro; Calderón-Salinas, José-Víctor

2014-01-01

The molecular response of the antioxidant system and the effects of antioxidant supplementation against oxidative insult in lead-exposed workers has not been sufficiently studied. In this work, antioxidants (vitamin E 400 IU+vitamin C 1g/daily) were supplemented for one year to 15 workers exposed to lead (73 μg of lead/dl of blood) and the results were compared with those on 19 non-lead exposed workers (6.7 μg of lead/dl). Lead intoxication was accompanied by a high oxidative damage and an increment in the erythrocyte antioxidant response due to increased activity of catalase and superoxide dismutase. Antioxidant supplementations decreased significantly the oxidative damage as well as the total antioxidant capacity induced by lead intoxication with reduction of the antioxidant enzyme activities. We conclude that antioxidant supplementation is effective in reducing oxidative damage and induces modifications in the physiopathological status of the antioxidant response in lead-exposed workers. Copyright © 2013 Elsevier B.V. All rights reserved.

MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys.

PubMed

Parajuli, Nirmala; Campbell, Lia H; Marine, Akira; Brockbank, Kelvin G M; Macmillan-Crow, Lee Ann

2012-01-01

Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation.

MitoQ Blunts Mitochondrial and Renal Damage during Cold Preservation of Porcine Kidneys

PubMed Central

Parajuli, Nirmala; Campbell, Lia H.; Marine, Akira; Brockbank, Kelvin G. M.; MacMillan-Crow, Lee Ann

2012-01-01

Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation. PMID:23139796

Differential p53 engagement in response to oxidative and oncogenic stresses in Fanconi anemia mice.

PubMed

Rani, Reena; Li, Jie; Pang, Qishen

2008-12-01

Members of the Fanconi anemia (FA) protein family are involved in repair of genetic damage caused by DNA cross-linkers. It is not clear whether the FA proteins function in oxidative DNA damage and oncogenic stress response. Here, we report that deficiency in the Fanca gene in mice elicits a p53-dependent growth arrest and DNA damage response to oxidative DNA damage and oncogenic stress. Using a Fanca-/-Trp53-/- double knockout model and a functionally switchable p53 retrovirus, we define the kinetics, dependence, and persistence of p53-mediated response to oxidative and oncogenic stresses in Fanca-/- cells. Notably, oxidative stress induces persistent p53 response in Fanca-/- cells, likely due to accumulation of unrepaired DNA damage. On the other hand, whereas wild-type cells exhibit prolonged response to oncogene activation, the p53-activating signals induced by oncogenic ras are short-lived in Fanca-/- cells, suggesting that Fanca may be required for the cell to engage p53 during constitutive ras activation. We propose that the FA proteins protect cells from stress-induced proliferative arrest and tumor evolution by acting as a modulator of the signaling pathways that link FA to p53.

Differential p53 engagement in response to oxidative and oncogenic stresses in Fanconi anemia mice

PubMed Central

Rani, Reena; Li, Jie; Pang, Qishen

2008-01-01

Members of the Fanconi anemia (FA) protein family are involved in repair of genetic damage caused by DNA cross-linkers. It is not clear whether the FA proteins function in oxidative DNA damage and oncogenic stress response. Here we report that deficiency in the Fanca gene in mice elicits a p53-dependent growth arrest and DNA damage response to oxidative DNA damage and oncogenic stress. Using a Fanca-/- Trp53-/- double knockout model and a functionally switchable p53 retrovirus, we define the kinetics, dependence, and persistence of p53-mediated response to oxidative and oncogenic stresses in Fanca-/- cells. Notably, oxidative stress induces persistent p53 response in Fanca-/- cells, likely due to accumulation of unrepaired DNA damage. On the other hand, whereas WT cells exhibit prolonged response to oncogene activation, the p53-activating signals induced by oncogenic ras are short-lived in Fanca-/- cells, suggesting that Fanca may be required for the cell to engage p53 during constitutive ras activation. We propose that the FA proteins protect cells from stress-induced proliferative arrest and tumor evolution by acting as a modulator of the signaling pathways that link FA to p53. PMID:19047147

Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.

PubMed

Kalghatgi, Sameer; Spina, Catherine S; Costello, James C; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S; Collins, James J

2013-07-03

Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics-quinolones, aminoglycosides, and β-lactams-cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic-induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.

Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

PubMed Central

Costello, James C.; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S.; Collins, James J.

2013-01-01

Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-L-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people. PMID:23825301

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Kinetics of membrane damage to high (HNA) and low (LNA) nucleic acid bacterial clusters in drinking water by ozone, chlorine, chlorine dioxide, monochloramine, ferrate(VI), and permanganate.

PubMed

Ramseier, Maaike K; von Gunten, Urs; Freihofer, Pietro; Hammes, Frederik

2011-01-01

Drinking water was treated with ozone, chlorine, chlorine dioxide, monochloramine, ferrate(VI), and permanganate to investigate the kinetics of membrane damage of native drinking water bacterial cells. Membrane damage was measured by flow cytometry using a combination of SYBR Green I and propidium iodide (SGI+PI) staining as indicator for cells with permeabilized membranes and SGI alone to measure total cell concentration. SGI+PI staining revealed that the cells were permeabilized upon relatively low oxidant exposures of all tested oxidants without a detectable lag phase. However, only ozonation resulted in a decrease of the total cell concentrations for the investigated reaction times. Rate constants for the membrane damage reaction varied over seven orders of magnitude in the following order: ozone > chlorine > chlorine dioxide ≈ ferrate > permanganate > chloramine. The rate constants were compared to literature data and were in general smaller than previously measured rate constants. This confirmed that membrane integrity is a conservative and therefore safe parameter for disinfection control. Interestingly, the cell membranes of high nucleic acid (HNA) content bacteria were damaged much faster than those of low nucleic acid (LNA) content bacteria during treatment with chlorine dioxide and permanganate. However, only small differences were observed during treatment with chlorine and chloramine, and no difference was observed for ferrate treatment. Based on the different reactivity of these oxidants it was suggested that HNA and LNA bacterial cell membranes have a different chemical constitution. Copyright © 2010 Elsevier Ltd. All rights reserved.

Oxidative stress and the evolution of sex differences in life span and ageing in the decorated cricket, Gryllodes sigillatus.

PubMed

Archer, Catharine R; Sakaluk, Scott K; Selman, Colin; Royle, Nick J; Hunt, John

2013-03-01

The Free Radical Theory of Ageing (FRTA) predicts that oxidative stress, induced when levels of reactive oxygen species exceed the capacity of antioxidant defenses, causes ageing. Recently, it has also been argued that oxidative damage may mediate important life-history trade-offs. Here, we use inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, life span, ageing, oxidative damage, and total antioxidant capacity within and between the sexes. The FRTA predicts that oxidative damage should accumulate with age and negatively correlate with life span. We find that protein oxidation is greater in the shorter lived sex (females) and negatively genetically correlated with life span in both sexes. However, oxidative damage did not accumulate with age in either sex. Previously we have shown antagonistic pleiotropy between the genes for early-life reproductive effort and ageing rate in both sexes, although this was stronger in females. In females, we find that elevated fecundity early in life is associated with greater protein oxidation later in life, which is in turn positively correlated with the rate of ageing. Our results provide mixed support for the FRTA but suggest that oxidative stress may mediate sex-specific life-history strategies in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Protective effect of Pterostilbene against free radical mediated oxidative damage

PubMed Central

2013-01-01

Background Pterostilbene, a methoxylated analog of Resveratrol, is gradually gaining more importance as a therapeutic drug owing to its higher lipophilicity, bioavailability and biological activity than Resveratrol. This study was undertaken to characterize its ability to scavenge free radicals such as superoxide, hydroxyl and hydrogen peroxide and to protect bio-molecules within a cell against oxidative insult. Methods Anti-oxidant activity of Pterostilbene was evaluated extensively by employing several in vitro radical scavenging/inhibiting assays and pulse radiolysis study. In addition, its ability to protect rat liver mitochondria against tertiary-butyl hydroperoxide (TBHP) and hydroxyl radical generated oxidative damage was determined by measuring the damage markers such as protein carbonyls, protein sulphydryls, lipid hydroperoxides, lipid peroxides and 8-hydroxy-2'-deoxyguanosine. Pterostilbene was also evaluated for its ability to inhibit •OH radical induced single strand breaks in pBR322 DNA. Result Pterostilbene exhibited strong anti-oxidant activity against various free radicals such as DPPH, ABTS, hydroxyl, superoxide and hydrogen peroxide in a concentration dependent manner. Pterostilbene conferred protection to proteins, lipids and DNA in isolated mitochondrial fractions against TBHP and hydroxyl radical induced oxidative damage. It also protected pBR322 DNA against oxidative assault. Conclusions Thus, present study provides an evidence for the strong anti-oxidant property of Pterostilbene, methoxylated analog of Resveratrol, thereby potentiating its role as an anti-oxidant. PMID:24070177

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

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

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

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

EROD activity, chromosomal damage, and oxidative stress in response to contaminants exposure in tree swallow (Tachycineta bicolor) nestlings from Great Lakes Areas of Concern

USGS Publications Warehouse

Custer, Thomas W.; Custer, Christine M.; Dummer, Paul; Bigorgne, Emilie; Oziolor, Elias; Karouna-Renier, Natalie K.; Schultz, Sandra; Erickson, Richard A.; Aagaard, Kevin; Matson, Cole W.

2017-01-01

Tree swallow, Tachycineta bicolor, nestlings were collected from 60 sites in the Great Lakes, which included multiple sites within 27 Areas of Concern (AOCs) and six sites not listed as AOCs from 2010 to 2014. Nestlings, approximately 12 days-of-age, were evaluated for ethoxyresorufin-O-dealkylase (EROD) activity, chromosomal damage, and six measures of oxidative stress. Data on each of these biomarkers were divided into four equal numbered groups from the highest to lowest values and the groups were compared to contaminant concentrations using multivariate analysis. Contaminant concentrations, from the same nestlings, included polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), and 17 elements. Alkylated polycyclic aromatic hydrocarbons (aPAHs) and parent PAHs (pPAHs) were measured in pooled nestling dietary samples. Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and pesticides were measured in sibling eggs. Concentrations of aPAHs, pPAHs, chlordane, dieldrin, heptachlor, and PCBs, in that order, were the major contributors to the significant differences between the lowest and highest EROD activities; PFCs, PBDEs, the remaining pesticides, and all elements were of secondary importance. The four categories of chromosomal damage did not separate out well based on the contaminants measured. Concentrations of aPAHs, pPAHs, heptachlor, PCBs, chlordane, and dieldrin were the major contributors to the significant differences between the lowest and highest activities of two oxidative stress measures, total sulfhydryl (TSH) activity and protein bound sulfhydryl (PBSH) activity. The four categories of thiobarbituric acid reacting substances (TBARS), oxidized glutathione (GSSG), reduced glutathione (GSH), and the ratio of GSSG/GSH did not separate well based on the contaminants measured.

Detection of Strand Cleavage And Oxidation Damage Using Model DNA Molecules Captured in a Nanoscale Pore

NASA Technical Reports Server (NTRS)

Vercoutere, W.; Solbrig, A.; DeGuzman, V.; Deamer, D.; Akeson, M.

2003-01-01

We use a biological nano-scale pore to distinguish among individual DNA hairpins that differ by a single site of oxidation or a nick in the sugar-phosphate backbone. In earlier work we showed that the protein ion channel alpha-hemolysin can be used as a detector to distinguish single-stranded from double-stranded DNA, single base pair and single nucleotide differences. This resolution is in part a result of sensitivity to structural changes that influence the molecular dynamics of nucleotides within DNA. The strand cleavage products we examined here included a 5-base-pair (5-bp) hairpin with a 5-prime five-nucleotide overhang, and a complementary five-nucleotide oligomer. These produced predictable shoulder-spike and rapid near-full blockade signatures, respectively. When combined, strand annealing was monitored in real time. The residual current level dropped to a lower discrete level in the shoulder-spike blockade signatures, and the duration lengthened. However, these blockade signatures had a shorter duration than the unmodified l0bp hairpin. To test the pore sensitivity to nucleotide oxidation, we examined a 9-bp hairpin with a terminal 8-oxo-deoxyguanosine (8-oxo-dG), or a penultimate 8-oxo-dG. Each produced blockade signatures that differed from the otherwise identical control 9bp hairpins. This study showed that DNA structure is modified sufficiently by strand cleavage or oxidation damage at a single site to alter in a predictable manner the ionic current blockade signatures produced. This technique improves the ability to assess damage to DNA, and can provide a simple means to help characterize the risks of radiation exposure. It may also provide a method to test radiation protection.

EROD activity, chromosomal damage, and oxidative stress in response to contaminants exposure in tree swallow (Tachycineta bicolor) nestlings from Great Lakes Areas of Concern.

PubMed

Custer, Thomas W; Custer, Christine M; Dummer, Paul M; Bigorgne, Emilie; Oziolor, Elias M; Karouna-Renier, Natalie; Schultz, Sandra; Erickson, Richard A; Aagaard, Kevin; Matson, Cole W

2017-12-01

Tree swallow, Tachycineta bicolor, nestlings were collected from 60 sites in the Great Lakes, which included multiple sites within 27 Areas of Concern (AOCs) and six sites not listed as AOCs from 2010 to 2014. Nestlings, approximately 12 days-of-age, were evaluated for ethoxyresorufin-O-dealkylase (EROD) activity, chromosomal damage, and six measures of oxidative stress. Data on each of these biomarkers were divided into four equal numbered groups from the highest to lowest values and the groups were compared to contaminant concentrations using multivariate analysis. Contaminant concentrations, from the same nestlings, included polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), and 17 elements. Alkylated polycyclic aromatic hydrocarbons (aPAHs) and parent PAHs (pPAHs) were measured in pooled nestling dietary samples. Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and pesticides were measured in sibling eggs. Concentrations of aPAHs, pPAHs, chlordane, dieldrin, heptachlor, and PCBs, in that order, were the major contributors to the significant differences between the lowest and highest EROD activities; PFCs, PBDEs, the remaining pesticides, and all elements were of secondary importance. The four categories of chromosomal damage did not separate out well based on the contaminants measured. Concentrations of aPAHs, pPAHs, heptachlor, PCBs, chlordane, and dieldrin were the major contributors to the significant differences between the lowest and highest activities of two oxidative stress measures, total sulfhydryl (TSH) activity and protein bound sulfhydryl (PBSH) activity. The four categories of thiobarbituric acid reacting substances (TBARS), oxidized glutathione (GSSG), reduced glutathione (GSH), and the ratio of GSSG/GSH did not separate well based on the contaminants measured.

Oxidation-Assisted Crack Growth in Single-Crystal Superalloys during Fatigue with Compressive Holds

NASA Astrophysics Data System (ADS)

Lafata, M. A.; Rettberg, L. H.; He, M. Y.; Pollock, T. M.

2018-01-01

The mechanism of oxidation-assisted growth of surface cracks during fatigue with compressive holds has been studied experimentally and via a model that describes the role of oxide and substrate properties. The creep-based finite element model has been employed to examine the role of material parameters in the damage evolution in a Ni-base single-crystal superalloy René N5. Low-cycle fatigue experiments with compressive holds were conducted at 1255 K and 1366 K (982 °C and 1093 °C). Interrupted and failed specimens were characterized for crack depth and spacing, oxide thickness, and microstructural evolution. Comparison of experimental to modeled hysteresis loops indicates that transient creep drives the macroscopic stress-strain response. Crack penetration rates are strongly influenced by growth stresses in the oxide, structural evolution in the substrate, and the development of γ ^' } denuded zones. Implications for design of alloys resistant to this mode of degradation are discussed.

Intracellular iron overload leading to DNA damage of lymphocytes and immune dysfunction in thalassemia major patients.

PubMed

Shaw, Jyoti; Chakraborty, Ayan; Nag, Arijit; Chattopadyay, Arnab; Dasgupta, Anjan K; Bhattacharyya, Maitreyee

2017-11-01

To investigate the cause and effects of intracellular iron overload in lymphocytes of thalassemia major patients. Sixty-six thalassemia major patients having iron overload and 10 age-matched controls were chosen for the study. Blood sample was collected, and serum ferritin, oxidative stress; lymphocyte DNA damage were examined, and infective episodes were also counted. Case-control analysis revealed significant oxidative stress, iron overload, DNA damage, and rate of infections in thalassemia cases as compared to controls. For cases, oxidative stress (ROS) and iron overload (serum ferritin) showed good correlation with R 2  = 0.934 and correlation between DNA damage and ROS gave R 2  = 0.961. We also demonstrated that intracellular iron overload in thalassemia caused oxidative damage of lymphocyte DNA as exhibited by DNA damage assay. The inference is further confirmed by partial inhibition of such damage by chelation of iron and the concurrent lowering of the ROS level in the presence of chelator deferasirox. Therefore, intracellular iron overload caused DNA fragmentation, which may ultimately hamper lymphocyte function, and this may contribute to immune dysfunction and increased susceptibility to infections in thalassemia patients as indicated by the good correlation (R 2  = 0.91) between lymphocyte DNA damage and rate of infection found in this study. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vitamin-E reduces the oxidative damage on delta-aminolevulinic dehydratase induced by lead intoxication in rat erythrocytes.

PubMed

Rendón-Ramirez, A; Cerbón-Solórzano, J; Maldonado-Vega, M; Quintanar-Escorza, M A; Calderón-Salinas, J V

2007-09-01

Lead intoxication induces oxidative damage on lipids and proteins. In the present paper we study in vivo and in vitro the antioxidant effect of vitamin-E and trolox, on the oxidative effects of lead intoxication in rat erythrocytes. Vitamin-E simultaneously administered to erythrocytes treated with lead was capable to prevent the inhibition of delta-aminolevulinic dehydratase activity and lipid oxidation. Partial but important protective effects were found when vitamin-E was administered either after or before lead exposure in rats. In vitro, the antioxidant trolox protected delta-ALA-D activity against damage induced by lead or menadione. These results indicate that vitamin-E could be useful in order to protect membrane-lipids and, notably, to prevent protein oxidation produced by lead intoxication.

Effect of DHA on plasma fatty acid availability and oxidative stress during training season and football exercise.

PubMed

Martorell, Miquel; Capó, Xavier; Sureda, Antoni; Batle, Joan M; Llompart, Isabel; Argelich, Emma; Tur, Josep A; Pons, Antoni

2014-08-01

The aim was to determine the effects of a diet supplemented with 1.14 g per day of docosahexaenoic acid (DHA) for eight weeks on the plasma oxidative balance and anti-inflammatory markers after training and acute exercise. Fifteen volunteer male football players were randomly assigned to placebo or experimental and supplemented groups. Blood samples were taken under resting conditions at the beginning and after eight weeks of training under resting and post-exercise conditions. The experimental beverage increased the plasma DHA availability in non-esterified fatty acids (NEFAs) and triglyceride fatty acids (TGFAs) and increased the polyunsaturated fatty acid (PUFA) fraction of NEFAs but had no effects on the biomarkers for oxidative balance in plasma. During training, plasma protein markers of oxidative damage, the haemolysis degree and the antioxidant enzyme activities increased, but did not affect lipid oxidative damage. Training season and DHA influenced the circulating levels of prostaglandin E2 (PGE2). Acute exercise did not alter the basal levels of plasma markers for oxidative and nitrosative damage of proteins and lipids, and the antioxidant enzyme activities, although DHA-diet supplementation significantly increased the PGE2 in plasma after acute exercise. In conclusion, the training season and acute exercise, but not the DHA diet supplementation, altered the pattern of plasma oxidative damage, as the antioxidant system proved sufficient to prevent the oxidative damage induced by the acute exercise in well-trained footballers. The DHA-diet supplementation increased the prostaglandin PGE2 plasma evidencing anti-inflammatory effects of DHA to control inflammation after acute exercise.

The Quinone Based Antitumor Agent Sepantronium Bromide (YM155) Causes Oxygen Independent Redox Activated Oxidative DNA Damage.

PubMed

Wani, Tasaduq Hussain; Surendran, Sreeraj; Jana, Anal; Chakrabarty, Anindita; Chowdhury, Goutam

2018-06-13

Sepantronium bromide (YM155) is a small molecule antitumor agent currently in phase II clinical trials. Although developed as survivin suppressor, YM155's primary mode of action has recently been found to be DNA damage. However, the mechanism of DNA damage by YM155 is still unknown. Knowing the mechanism of action of an anticancer drug is necessary to formulate a rational drug combination and select a cancer type for achieving maximum clinical efficacy. Using cell-based assays we showed that YM155 cause extensive DNA cleavage and reactive oxygen species generation. DNA cleavage by YM155 was found to be inhibited by radical scavengers and desferal. The reducing agent DTT and the cellular reducing system xanthine/xanthine oxidase were found to reductively activate YM155 and cause DNA cleavage. Unlike quinones, DNA cleavage by YM155 occurs in the presence of catalase and under hypoxic conditions indicating that hydrogen peroxide and oxygen is not necessary. Although YM155 is a quinone, it does not follow a typical quinone mechanism. Consistent with these observations a mechanism has been proposed that suggests that YM155 can cause oxidative DNA cleavage upon two electron reductive activation.

Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

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

Grollman, A.P.; Takeshita, Masaru

1995-12-31

More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura`s discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10{sup 5} guanine residues in mammalian DNA are oxidized atmore » the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA.« less

Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.

PubMed

Petrović, Anja; Bogojević, Desanka; Korać, Aleksandra; Golić, Igor; Jovanović-Stojanov, Sofija; Martinović, Vesna; Ivanović-Matić, Svetlana; Stevanović, Jelena; Poznanović, Goran; Grigorov, Ilijana

2017-11-01

The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.

Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats.

PubMed

Cioffi, Federica; Senese, Rosalba; Lasala, Pasquale; Ziello, Angela; Mazzoli, Arianna; Crescenzo, Raffaella; Liverini, Giovanna; Lanni, Antonia; Goglia, Fernando; Iossa, Susanna

2017-03-24

Evidence indicates that many forms of fructose-induced metabolic disturbance are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage; however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are events involved in metabolic disease resulting from a fructose-rich diet. In the present study, we evaluated the degree of oxidative damage to liver mtDNA and its repair, in addition to the state of oxidative stress and antioxidant defense in the liver of rats fed a high-fructose diet. We used male rats feeding on a high-fructose or control diet for eight weeks. Our results showed an increase in mtDNA damage in the liver of rats fed a high-fructose diet and this damage, as evaluated by the expression of DNA polymerase γ, was not repaired; in addition, the mtDNA copy number was found to be significantly reduced. A reduction in the mtDNA copy number is indicative of impaired mitochondrial biogenesis, as is the finding of a reduction in the expression of genes involved in mitochondrial biogenesis. In conclusion, a fructose-rich diet leads to mitochondrial and mtDNA damage, which consequently may have a role in liver dysfunction and metabolic diseases.

Integrated approach for stress based lifing of aero gas turbine blades

NASA Astrophysics Data System (ADS)

Abu, Abdullahi Obonyegba

In order to analyse the turbine blade life, the damage due to the combined thermal and mechanical loads should be adequately accounted for. This is more challenging when detailed component geometry is limited. Therefore, a compromise between the level of geometric detail and the complexity of the lifing method to be implemented would be necessary. This research focuses on how the life assessment of aero engine turbine blades can be done, considering the balance between available design inputs and adequate level of fidelity. Accordingly, the thesis contributes to developing a generic turbine blade lifing method that is based on the engine thermodynamic cycle; as well as integrating critical design/technological factors and operational parameters that influence the aero engine blade life. To this end, thermo-mechanical fatigue was identified as the critical damage phenomenon driving the life of the turbine blade.. The developed approach integrates software tools and numerical models created using the minimum design information typically available at the early design stages. Using finite element analysis of an idealised blade geometry, the approach captures relevant impacts of thermal gradients and thermal stresses that contribute to the thermo-mechanical fatigue damage on the gas turbine blade. The blade life is evaluated using the Neu/Sehitoglu thermo-mechanical fatigue model that considers damage accumulation due to fatigue, oxidation, and creep. The leading edge is examined as a critical part of the blade to estimate the damage severity for different design factors and operational parameters. The outputs of the research can be used to better understand how the environment and the operating conditions of the aircraft affect the blade life consumption and therefore what is the impact on the maintenance cost and the availability of the propulsion system. This research also finds that the environmental (oxidation) effect drives the blade life and the blade coolant side was the critical location. Furthermore, a parametric and sensitivity study of the Neu/Sehitoglu model parameters suggests that in addition to four previously reported parameters, the sensitivity of the phasing to oxidation damage would be critical to overall blade life..

Effects of flight activity and age on oxidative damage in the honey bee, Apis mellifera.

PubMed

Margotta, Joseph W; Roberts, Stephen P; Elekonich, Michelle M

2018-05-03

Frequent and highly aerobic behaviors likely contribute to naturally occurring stress, accelerate senescence, and limit lifespan. To understand how the physiological and cellular mechanisms that determine the onset and duration of senescence are shaped by behavioral development and behavioral duration, we exploited the tractability of the honey bee ( Apis mellifera ) model system. First, we determined if a cause-effect relationship exists between honey bee flight and oxidative stress by comparing oxidative damage accrued from intense flight bouts to damage accrued from D-galactose ingestion, which induces oxidative stress and limit lifespan in other insects. Second, we experimentally manipulated the duration of honey bee flight across a range of ages to determine their effects on reactive oxygen species (ROS) accumulation and associated enzymatic antioxidant protective mechanisms. In bees fed D-galactose, lipid peroxidation (MDA) was higher than in bees fed sucrose and age-matched bees with high and low flight experience collected from a colony. Bees with high amounts of flight experience exhibited elevated 8-OHdG, a marker of oxidative DNA damage, relative to bees with less flight experience. Bees with high amounts of flight experience also showed increased levels of pro-oxidants (superoxide and H 2 O 2 ) and decreased or unchanged levels of antioxidants (SOD and catalase). These data implicate an imbalance of pro- to antioxidants in flight-associated oxidative stress and reveal how behavior can damage a cell and consequently limit lifespan. © 2018. Published by The Company of Biologists Ltd.

Oxidative Stress Mechanisms Do Not Discriminate between Genotoxic and Nongenotoxic Liver Carcinogens.

PubMed

Deferme, Lize; Wolters, Jarno; Claessen, Sandra; Briedé, Jacco; Kleinjans, Jos

2015-08-17

It is widely accepted that in chemical carcinogenesis different modes-of-action exist, e.g., genotoxic (GTX) versus nongenotoxic (NGTX) carcinogenesis. In this context, it has been suggested that oxidative stress response pathways are typical for NGTX carcinogenesis. To evaluate this, we examined oxidative stress-related changes in gene expression, cell cycle distribution, and (oxidative) DNA damage in human hepatoma cells (HepG2) exposed to GTX-, NGTX-, and noncarcinogens, at multiple time points (4-8-24-48-72 h). Two GTX (azathriopine (AZA) and furan) and two NGTX (tetradecanoyl-phorbol-acetate, (TPA) and tetrachloroethylene (TCE)) carcinogens as well as two noncarcinogens (diazinon (DZN, d-mannitol (Dman)) were selected, while per class one compound was deemed to induce oxidative stress and the other not. Oxidative stressors AZA, TPA, and DZN induced a 10-fold higher number of gene expression changes over time compared to those of furan, TCE, or Dman treatment. Genes commonly expressed among AZA, TPA, and DZN were specifically involved in oxidative stress, DNA damage, and immune responses. However, differences in gene expression between GTX and NGTX carcinogens did not correlate to oxidative stress or DNA damage but could instead be assigned to compound-specific characteristics. This conclusion was underlined by results from functional readouts on ROS formation and (oxidative) DNA damage. Therefore, oxidative stress may represent the underlying cause for increased risk of liver toxicity and even carcinogenesis; however, it does not discriminate between GTX and NGTX carcinogens.

Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

PubMed

Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

2013-09-01

The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

Antioxidant and anti-ageing activities of citrus-based juice mixture.

PubMed

Kim, Dan-Bi; Shin, Gi-Hae; Kim, Jae-Min; Kim, Young-Hyun; Lee, Jin-Ha; Lee, Jong Seok; Song, Hye-Jin; Choe, Soo Young; Park, In-Jae; Cho, Ju-Hyun; Lee, Ok-Hawn

2016-03-01

The production of excessive reactive oxygen species by exposure to oxidative stress and solar radiation are primary factors in skin damage. We examined the effects of a citrus-based juice mixture and its bioactive compounds on antioxidant and anti-ageing activities in human dermal fibroblasts and hairless mice via the regulation of antioxidant enzymes and the mitogen-activated protein kinase pathway. The citrus-based juice mixture reduced H2O2-induced cell damage and intracellular reactive oxygen species production in human dermal fibroblasts. Citrus-based juice mixture pretreatment suppressed the activation of the H2O2-mediated mitogen-activated protein kinase pathway by activating the expression of activator protein 1 and matrix metalloproteinases. Moreover, it increased the expression levels of antioxidant enzymes such as glutathione reductase, catalase and manganese superoxide dismutase. In addition, oral administration of the citrus-based juice mixture decreased skin thickness and wrinkle formation and increased collagen content on an ultraviolet light B-exposed hairless mouse. These results indicate that the citrus-based juice mixture is a potentially healthy beverage for the prevention of oxidative stress-induced premature skin ageing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

PubMed Central

Rodríguez-Lara, Simón Quetzalcoatl; Ramírez-Lizardo, Ernesto Javier; Totsuka-Sutto, Sylvia Elena; Castillo-Romero, Araceli; García-Cobián, Teresa Arcelia

2016-01-01

Ischemia/reperfusion (I/R) lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states. PMID:28116037

Risk of Oxidative Damage to Bone from Increased Iron Stores During Space Flight

NASA Technical Reports Server (NTRS)

Zwart, S. R.; Smith, S. M.

2014-01-01

Iron stores are increased secondary to neocytolysis of red blood cells and a high dietary intake of iron during space flight. This raises concerns about the risk of excess iron causing oxidative damage in many tissues, including bone. Biomarkers of iron status, oxidative damage, and bone resorption during space flight were analyzed for 23 (16 M/7 F) International Space Station crewmembers as part of the Nutrition SMO project. Up to 5 in-flight blood samples and 24-h urine pools were collected over the course of the 4-6 month missions. Serum iron increased slightly during space flight and was decreased at landing (P < 0.0004). An increase in serum ferritin early in flight (217% in women and 68% in men, P < 0.0004), returning to preflight concentrations at landing, and a decrease in transferrin and transferrin receptors during flight indicated that a transient increase in iron stores occurred. No inflammatory response was observed during flight. The oxidative damage markers 8-hydroxy-2'-deoxyguanosine and prostaglandin F(sub 2(alpha)) were positively correlated (both P < 0.001) with serum ferritin. A greater area under the curve for ferritin during flight was correlated with greater changes in bone mineral density of several bone regions after flight (1). In a separate study (2), a ground-based investigation was conducted that examined the combined effects of radiation exposure and iron overload on sensitivity to radiation injury in several physiological systems in 12-wk male Sprague-Dawley rats. The rats were acclimated to an adequate iron diet (45 mg iron (ferric citrate)/kg diet) for 3 wk and then assigned to one of four groups: adequate iron (Fe) diet/no radiation, adequate Fe diet/ radiation, moderately high Fe diet (650 mg Fe (ferric citrate)/kg diet)/no radiation, and moderately high Fe diet/radiation. Animals remained on the assigned diet for 4 wk. Starting on day 14 of experimental diet treatment, animals were exposed to a fractionated dose (0.375 Gy) of Cs-137 every other day (3 Gy total dose). On day 29 (24 h after last radiation exposure), animals were euthanized. Oxidative stress markers in the liver, bone, eyes, and serum were assessed. There was evidence that the iron diet contributed to DNA damage as well as radiation exposure in the liver, eyes, and bone. Together, the results suggest that increased iron stores do constitute a risk factor for oxidative damage and bone resorption, during space flight and on Earth. Funded by the Human Health and Countermeasures Element of the NASA Human Research Program.

Circadian Modulation of 8-Oxoguanine DNA Damage Repair

PubMed Central

Manzella, Nicola; Bracci, Massimo; Strafella, Elisabetta; Staffolani, Sara; Ciarapica, Veronica; Copertaro, Alfredo; Rapisarda, Venerando; Ledda, Caterina; Amati, Monica; Valentino, Matteo; Tomasetti, Marco; Stevens, Richard G.; Santarelli, Lory

2015-01-01

The DNA base excision repair pathway is the main system involved in the removal of oxidative damage to DNA such as 8-Oxoguanine (8-oxoG) primarily via the 8-Oxoguanine DNA glycosylase (OGG1). Our goal was to investigate whether the repair of 8-oxoG DNA damage follow a circadian rhythm. In a group of 15 healthy volunteers, we found a daily variation of Ogg1 expression and activity with higher levels in the morning compared to the evening hours. Consistent with this, we also found lower levels of 8-oxoG in morning hours compared to those in the evening hours. Lymphocytes exposed to oxidative damage to DNA at 8:00 AM display lower accumulation of 8-oxoG than lymphocytes exposed at 8:00 PM. Furthermore, altered levels of Ogg1 expression were also observed in a group of shift workers experiencing a deregulation of circadian clock genes compared to a control group. Moreover, BMAL1 knockdown fibroblasts with a deregulated molecular clock showed an abolishment of circadian variation of Ogg1 expression and an increase of OGG1 activity. Our results suggest that the circadian modulation of 8-oxoG DNA damage repair, according to a variation of Ogg1 expression, could render humans less susceptible to accumulate 8-oxoG DNA damage in the morning hours. PMID:26337123

Ballet dancers cardiorespiratory, oxidative and muscle damage responses to classes and rehearsals.

PubMed

Rodrigues-Krause, Josianne; Krause, Mauricio; Cunha, Giovani Dos Santos; Perin, Diana; Martins, Jocelito B; Alberton, Cristine Lima; Schaun, Maximiliano I; De Bittencourt, Paulo Ivo Homem; Reischak-Oliveira, Alvaro

2014-01-01

This study aimed to describe and compare ballet dancers' cardiorespiratory responses, muscle damage and oxidative stress levels during a ballet class (practice of isolated ballet exercises performed with barre/hand-rail support and across-the-floor movements to improve technical skills) and rehearsal (practice of ballet choreography involving technical-artistic skills to improve dancers' performance for shows). The 12 advanced female ballet dancers undertook three exercise sessions: maximum effort test, class and rehearsal. Heart rate (HR) and oxygen consumption (VO2) were continuously measured. Lactate was determined before 15 min and after class and rehearsal. Blood was sampled pre, post and 48 h after class and rehearsal for creatine kinase (CK), lipid peroxides (LPO) and glutathione analysis (GSSG/GSH). Class was of lower intensity than rehearsal as shown by VO2, HR and lactate values: VO2 (mL.kg(-1).min(-1)): 14.5±2.1 vs. 19.1±1.7 (p < 0.001); HR (bpm.min(-1)): 145.7±17.9 vs. 174.5±13.8 (p < 0.001); lactate (mmol.L(-1)): 4.2±1.1 vs. 5.5±2.7 (p = 0.049). CK (IU) increased following class and rehearsal, remaining high 48 h after: class (pre = 109.3±48.5; post = 144±60; 48 h = 117.2±64.6); rehearsal (pre = 78.6±52.1; post = 122±70.7; 48 h = 104.9±89.5). LPO (µM) increased from pre-class (1.27±0.19) to post-class (1.41±0.19) and went down after 48 h (1.20±0.22). No LPO time-course changes followed the rehearsal. GSSG/GSH decreased 48 h after class and rehearsal. Greater increases in LPO post-class suggest it promotes CK release by an oxidative membrane-damage mechanism. Physiological increases of LPO and CK in class indicate it prepares the dancers for exercise-induced oxidative stress and muscle damage during rehearsals. Ballet dancers' muscle damage and oxidative stress responses seem not to be dependent on exercise intensity based on VO2 responses.

Metal Oxide Silicon /MOS/ transistors protected from destructive damage by wire

NASA Technical Reports Server (NTRS)

Deboo, G. J.; Devine, E. J.

1966-01-01

Loop of flexible, small diameter, nickel wire protects metal oxide silicon /MOS/ transistors from a damaging electrostatic potential. The wire is attached to a music-wire spring, slipped over the MOS transistor case, and released so the spring tensions the wire loop around all the transistor leads, shorting them together. This allows handling without danger of damage.

Allicin enhances the oxidative damage effect of amphotericin B against Candida albicans.

PubMed

An, MaoMao; Shen, Hui; Cao, YongBing; Zhang, JunDong; Cai, Yun; Wang, Rui; Jiang, YuanYing

2009-03-01

Amphotericin B (AmB) is the gold standard of antifungal treatment for the most severe invasive mycoses. In addition to the interaction of AmB with ergosterol in the fungi cell membrane, several studies have demonstrated oxidative damage involved in the fungicidal activity of AmB. In this study, allicin, an allyl sulphur compound from garlic, was shown to enhance significantly the effect of AmB against Candida albicans in vitro and in vivo, although allicin did not exert a fungicidal effect. Further study first demonstrated that allicin-mediated oxidative damage, such as phospholipid peroxidation in the plasma membrane, via influencing the defence of C. albicans against oxidative damage may be the cause of the synergistic interaction between allicin and AmB. We envision that a combination of AmB with allicin may prove to be a promising strategy for the therapy of disseminated candidiasis.

Induction of oxidative DNA damage in anaerobes.

PubMed

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

1999-05-07

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

Wavelength dependence of biological damage induced by UV radiation on bacteria.

PubMed

Santos, Ana L; Oliveira, Vanessa; Baptista, Inês; Henriques, Isabel; Gomes, Newton C M; Almeida, Adelaide; Correia, António; Cunha, Ângela

2013-01-01

The biological effects of UV radiation of different wavelengths (UVA, UVB and UVC) were assessed in nine bacterial isolates displaying different UV sensitivities. Biological effects (survival and activity) and molecular markers of oxidative stress [DNA strand breakage (DSB), generation of reactive oxygen species (ROS), oxidative damage to proteins and lipids, and the activity of antioxidant enzymes catalase and superoxide dismutase] were quantified and statistically analyzed in order to identify the major determinants of cell inactivation under the different spectral regions. Survival and activity followed a clear wavelength dependence, being highest under UVA and lowest under UVC. The generation of ROS, as well as protein and lipid oxidation, followed the same pattern. DNA damage (DSB) showed the inverse trend. Multiple stepwise regression analysis revealed that survival under UVA, UVB and UVC wavelengths was best explained by DSB, oxidative damage to lipids, and intracellular ROS levels, respectively.

Wheat peptides reduce oxidative stress and inhibit NO production through modulating μ-opioid receptor in a rat NSAID-induced stomach damage model.

PubMed

Yin, Hong; Cai, Hui-Zhen; Wang, Shao-Kang; Yang, Li-Gang; Sun, Gui-Ju

2015-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) induce tissue damage and oxidative stress in animal models of stomach damage. In the present study, the protective effects of wheat peptides were evaluated in a NSAID-induced stomach damage model in rats. Different doses of wheat peptides or distilled water were administered daily by gavage for 30 days before the rat stomach damage model was established by administration of NSAIDs (aspirin and indomethacin) into the digestive tract twice. The treatment of wheat peptides decreased the NSAID-induced gastric epithelial cell degeneration and oxidative stress and NO levels in the rats. Wheat peptides significantly increased the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and decreased iNOS activity in stomach. The mRNA expression level of μ-opioid receptor was significantly decreased in wheat peptides-treated rats than that in in the control rats. The results suggest that NSAID drugs induced stomach damage in rats, wchih can be prevented by wheat peptides. The mechanisms for the protective effects were most likely through reducing NSAID-induced oxidative stress. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Effect of date seeds on oxidative damage and antioxidant status in vivo.

PubMed

Habib, Hosam M; Ibrahim, Wissam H

2011-07-01

Date seeds have been shown to contain high amounts of antioxidants. However, in vivo studies on date seeds are lacking. Therefore the purpose of this study was to determine the effect of date seeds on oxidative damage and antioxidant status in vivo. Male Wistar rats were fed a basal diet containing 0, 70 or 140 g kg(-1) date seeds for 30 days. All three diets were isonitrogenous and isocaloric. Indication of oxidative damage was assessed in the liver and serum, and antioxidant status was assessed in the liver. Serum biochemical parameters, including indicators of tissue cellular damage and complete blood count with differential, were also determined. The results showed that date seeds significantly (P<0.05) reduced liver and serum malondialdehyde (a lipid peroxidative damage product) and serum lactate dehydrogenase and creatine kinase. Liver antioxidants (vitamin E, vitamin C, glutathione, superoxide dismutase, glutathione peroxidase and catalase), complete blood count with differential and other serum biochemical parameters assessed were not significantly altered by date seeds. The results obtained suggest a protective effect of date seeds against in vivo oxidative damage, possibly through the action of their bioactive antioxidants. Copyright © 2011 Society of Chemical Industry.

The role of contamination history and gender on the genotoxic responses of the crayfish Procambarus clarkii to a penoxsulam-based herbicide.

PubMed

Costa, Ricardo; Pereira, Joana Luísa; Santos, Maria Ana; Pacheco, Mário; Guilherme, Sofia

2018-06-04

The responses of non-target organisms to pesticide exposure are still poorly explored in what concerns the development of adjustments favouring population success. Owing to the vital role of DNA integrity, it is important to identify genome-maintenance skills and their determinant factors. Thus, the major aims of the present study were: (i) to assess the genotoxicity of the penoxsulam-based herbicide (Viper ® ) to the crayfish Procambarus clarkii; (ii) to understand the influence of gender and contamination history in the genotoxic responses following exposure to this herbicide; (iii) to investigate the damage mechanisms involved in putative adjustments shown by P. clarkii. Two populations were tested, one from a reference site and the other from a historically contaminated site. Specimens from both populations were exposed to Viper ® , considering environmentally relevant penoxsulam concentrations (20 and 40 µg L -1 ) and to a model genotoxicant (EMS). Comet assay was adopted to assess the genetic damage in gills. The results disclosed the genotoxicity of the herbicide to crayfish (a non-target organism). Additionally, organisms exposed to the highest concentration of penoxsulam signalized the influence of factor "population" towards the genotoxic pressure (measured as effective DNA breaks): P2 males from the historically impacted population displayed a significantly higher susceptibly (by up to 53.98%) when compared to control, while the homologous group from the reference population presented levels similar to its respective control. When DNA lesion-repair enzymes were considered, DNA oxidation patterns suggested an increased ability of this gender (39.75% lower than negative control) to deal with this particular type of damage, namely considering pyrimidines oxidation. It is worth remarking that the influence of the exposure history on the protection/vulnerability to the penoxsulam-based herbicide was only evident in males, despite depending on the type of DNA damage: when the non-specific damage was considered, organisms from the impacted population seemed to be more vulnerable while regarding to the oxidative damage, males from the impacted population appeared to be more protected than organisms that have never been exposed to penoxsulam. Overall, the influence of factors "gender" and "contamination history" was demonstrated as well as its dependence on DNA damage type was evident. EMS groups did not present the differences between populations, reinforcing the agent-specific adjustment hypothesis.These findings highlighted the importance of considering differential physiological backgrounds in ecogenotoxicological analysis, hence favouring the elaboration of more plausible and holistic approaches integrating the environmental risk assessment of pesticides.

A high accuracy femto-/picosecond laser damage test facility dedicated to the study of optical thin films

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

Mangote, B.; Gallais, L.; Zerrad, M.

2012-01-15

A laser damage test facility delivering pulses from 100 fs to 3 ps and designed to operate at 1030 nm is presented. The different details of its implementation and performances are given. The originality of this system relies the online damage detection system based on Nomarski microscopy and the use of a non-conventional energy detection method based on the utilization of a cooled CCD that offers the possibility to obtain the laser induced damage threshold (LIDT) with high accuracy. Applications of this instrument to study thin films under laser irradiation are presented. Particularly the deterministic behavior of the sub-picosecond damagemore » is investigated in the case of fused silica and oxide films. It is demonstrated that the transition of 0-1 damage probability is very sharp and the LIDT is perfectly deterministic at few hundreds of femtoseconds. The damage process in dielectric materials being the results of electronic processes, specific information such as the material bandgap is needed for the interpretation of results and applications of scaling laws. A review of the different approaches for the estimation of the absorption gap of optical dielectric coatings is conducted and the results given by the different methods are compared and discussed. The LIDT and gap of several oxide materials are then measured with the presented instrument: Al{sub 2}O{sub 3}, Nb{sub 2}O{sub 5}, HfO{sub 2}, SiO{sub 2}, Ta{sub 2}O{sub 5}, and ZrO{sub 2}. The obtained relation between the LIDT and gap at 1030 nm confirms the linear evolution of the threshold with the bandgap that exists at 800 nm, and our work expands the number of tested materials.« less

Oxidative stress damage as a detrimental factor in preterm birth pathology.

PubMed

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal-fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways.

Oxidative Stress Damage as a Detrimental Factor in Preterm Birth Pathology

PubMed Central

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal–fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways. PMID:25429290

Effects of Methylsulfonylmethane (MSM) on exercise-induced oxidative stress, muscle damage, and pain following a half-marathon: a double-blind, randomized, placebo-controlled trial.

PubMed

Withee, Eric D; Tippens, Kimberly M; Dehen, Regina; Tibbitts, Deanne; Hanes, Douglas; Zwickey, Heather

2017-01-01

Oxidative stress and muscle damage occur during exhaustive bouts of exercise, and many runners report pain and soreness as major influences on changes or breaks in training regimens, creating a barrier to training persistence. Methylsulfonylmethane (MSM) is a sulfur-based nutritional supplement that is purported to have pain and inflammation-reducing effects. To investigate the effects of MSM in attenuating damage associated with physical exertion, this randomized, double-blind, placebo-controlled study evaluated the effects of MSM supplementation on exercise-induced pain, oxidative stress and muscle damage. Twenty-two healthy females ( n  = 17) and males ( n  = 5) (age 33.7 ± 6.9 yrs.) were recruited from the 2014 Portland Half-Marathon registrant pool. Participants were randomized to take either MSM (OptiMSM®) ( n  = 11), or a placebo ( n  = 11) at 3 g/day for 21 days prior to the race and for two days after (23 total). Participants provided blood samples for measurement of markers of oxidative stress, and completed VAS surveys for pain approximately one month prior to the race (T 0 ), and at 15 min (T 1 ), 90 min (T 2 ), 1 Day (T 3 ), and 2 days (T 4 ) after race finish. The primary outcome measure 8-hydroxy-2-deoxyguanine (8-OHdG) measured oxidative stress. Secondary outcomes included malondialdehyde (MDA) for oxidative stress, creatine kinase (CK) and lactate dehydrogenase (LDH) as measures of muscle damage, and muscle (MP) and joint pain (JP) recorded using a 100 mm Visual Analogue Scale (VAS). Data were analyzed using repeated and multivariate ANOVAs, and simple contrasts compared post-race time points to baseline, presented as mean (SD) or mean change (95% CI) where appropriate. Running a half-marathon induced significant increases in all outcome measures ( p  < 0.001). From baseline, 8-OHdG increased significantly at T 1 by 1.53 ng/mL (0.86-2.20 ng/mL CI, p  < 0.001) and T 2 by 1.19 ng/mL (0.37-2.01 ng/mL CI, p  < 0.01), and fell below baseline levels at T 3 by -0.46 ng/mL (-1.18-0.26 CI, p  > 0.05) and T 4 by -0.57 ng/mL (-1.27-0.13 CI, p  > 0.05). MDA increased significantly at T 1 by 7.3 μM (3.9-10.7 CI, p  < 0.001). Muscle damage markers CK and LDH saw significant increases from baseline at all time-points ( p  < 0.01). Muscle and joint pain increased significantly from baseline at T 1 , T 2 , and T 3 ( p  < 0.01) and returned to baseline levels at T 4 . Time-by-treatment results did not reach statistical significance for any outcome measure, however, the MSM group saw clinically significant (Δ > 10 mm) reductions in both muscle and joint pain. Participation in a half-marathon was associated with increased markers of oxidative stress, muscle damage, and pain. MSM supplementation was not associated with a decrease from pre-training levels of oxidative stress or muscle damage associated with an acute bout of exercise. MSM supplementation attenuated post-exercise muscle and joint pain at clinically, but not statistically significant levels.

Electrochemical activity evaluation of chemically damaged carbon nanotube with palladium nanoparticles for ethanol oxidation

NASA Astrophysics Data System (ADS)

Ahmed, Mohammad Shamsuddin; Jeon, Seungwon

2015-05-01

The carbon nanotube (CNT) has unique electrical and structural properties due to it's sp2 π-conjugative structure that leads to the higher electrocatalysis. The π-conjugative structure, that allows the CNT interact with various compounds and metal nanoparticles (NPs) through π-π electronic interaction. However, the damage of π-conjugative sidewall of CNT that can be hinder the electrocatalytic activity has found. For this study, the CNT, as base material, has been prepared through a conventional acid treatment method up to 15 h; the higher degree of sidewall damage has been observed in last 5 h during treatment period. The short and long term acid treated (denoted as CNT and CNT-COOH, respectively) CNTs have been subsequently fabricated with palladium NPs (denoted as CNT/Pd and CNT-Pd, respectively) and employed as ethanol oxidation reaction (EOR) catalysts. The CNT-Pd displays a poor electrocatalytic performance towards EOR than that of CNT/Pd due to the damage of π-conjugative sidewall. The kinetic parameters including poisoning tolerance have also been hampered by the surface damage. The CNT/Pd (∼3.3 folds) and CNT-Pd (∼1.5 folds) are express higher electrocatalytic activity and poisoning tolerance than that of Pd/C while Pd mass loading remains in the same amount.

High-Intensity Exercise Induced Oxidative Stress and Skeletal Muscle Damage in Postpubertal Boys and Girls: A Comparative Study.

PubMed

Pal, Sangita; Chaki, Biswajit; Chattopadhyay, Sreya; Bandyopadhyay, Amit

2018-04-01

Pal, S, Chaki, B, Chattopadhyay, S, and Bandyopadhyay, A. High-intensity exercise induced oxidative stress and skeletal muscle damage in post-pubertal boys and girls: a comparative study. J Strength Cond Res 32(4): 1045-1052, 2018-The purpose of this study was to examine the sex variation in high-intensity exercise induced oxidative stress and muscle damage among 44 sedentary postpubertal boys and girls through estimation of postexercise release pattern of muscle damage markers like creatine kinase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and oxidative stress markers like extent of lipid peroxidation (thiobarbituric acid-reactive substances) and catalase activity. Muscle damage markers like creatine kinase, LDH, ALT, and AST were measured before, immediately after, and 24 and 48 hours after high-intensity incremental treadmill running. Oxidative stress markers like thiobarbituric acid-reactive substances and catalase activity were estimated before and immediately after the exercise. Lipid peroxidation and serum catalase activity increased significantly in both groups after exercise (p < 0.001) with postexercise values and percentage increase significantly higher in postpubertal boys as compared to girls (p < 0.001). Creatine kinase and LDH activity also increased significantly above pre-exercise level at 24 and 48 hours after exercise in both the sexes, (p < 0.001) with values significantly higher for boys than the girls (p < 0.001). Although ALT and AST increased significantly in both the groups after exercise, the pattern of postexercise release of these markers were found to be similar in both the groups. Accordingly, it has been concluded from the present investigation that high-intensity exercise induces significant oxidative stress and increases indices of skeletal muscle damage in both postpubertal girls and boys. However, postpubertal girls are relatively better protected from oxidative stress and muscle damage as compared to the boys of similar age and physical activity level. It is further evident that sex difference may not be apparent for all the biomarkers of muscle damage in this age group.

Oxidative damage in response to natural levels of UV-B radiation in larvae of the tropical sea urchin Tripneustes gratilla.

PubMed

Lister, Kathryn Naomi; Lamare, Miles D; Burritt, David J

2010-01-01

To assess the effects of UV radiation (280-400nm) on development, oxidative damage and antioxidant defence in larvae of the tropical sea urchin Tripneustes gratilla, a field experiment was conducted at two depths in Aitutaki, Cook Islands (18.85°S, 159.75°E) in May 2008. Compared with field controls (larvae shielded from UV-R but exposed to VIS-radiation), UV-B exposure resulted in developmental abnormality and increases in oxidative damage to proteins (but not lipids) in embryos of T. gratilla held at 1m depth. Results also indicated that larvae had the capacity to increase the activities of protective antioxidant enzymes when exposed to UV-B. The same trends in oxidative damage and antioxidant defence were observed for embryos held at 4m, although the differences were smaller and more variable. In contrast to UV-B exposure, larvae exposed to UV-A only showed no significant increases in abnormality or oxidative damage to lipids and proteins compared with field controls. This was true at both experimental depths. Furthermore, exposure to UV-A did not cause a significant increase in the activities of antioxidants. This study indicates that oxidative stress is an important response of tropical sea urchin larvae to exposure to UV radiation. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Effects of tempol and redox-cycling nitroxides in models of oxidative stress

PubMed Central

Wilcox, Christopher S.

2010-01-01

Tempol is a redox cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia. PMID:20153367

Renal damage mediated by oxidative stress: a hypothesis of protective effects of red wine.

PubMed

Rodrigo, Ramón; Rivera, Gonzalo

2002-08-01

Over the last decade, oxidative stress has been implicated in the pathogenesis of a wide variety of seemingly unrelated renal diseases. Epidemiological studies have documented an association of moderate wine consumption with a decreased risk of cardiovascular and neurological diseases; however, similar studies in the kidney are still lacking. The kidney is an organ highly vulnerable to damage caused by reactive oxygen species (ROS), likely due to the abundance of polyunsaturated fatty acids in the composition of renal lipids. ROS are involved in the pathogenic mechanism of conditions such as glomerulosclerosis and tubulointerstitial fibrosis. The health benefits of moderate consumption of red wine can be partly attributed to its antioxidant properties. Indeed, the kidney antioxidant defense system is enhanced after chronic exposure to moderate amounts of wine, a response arising from the combined effects of ethanol and the nonalcoholic components, mainly polyphenols. Polyphenols behave as potent ROS scavengers and metal chelators; ethanol, in turn, modulates the activity of antioxidant enzymes. Therefore, a hypothesis that red wine causes a decreased vulnerability of the kidney to the oxidative challenges could be proposed. This view is partly supported by direct evidences indicating that wine and antioxidants isolated from red wine, as well as other antioxidants, significantly attenuate or prevent the oxidative damage to the kidney. The present hypothesis paper provides a collective body of evidence suggesting a protective role of moderate wine consumption against the production and progression of renal diseases, based on the existing concepts on the pathophysiology of kidney injury mediated by oxidative stress.

Induction of NEIL1 and NEIL2 DNA glycosylases in aniline-induced splenic toxicity

PubMed Central

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

2011-01-01

The mechanisms by which aniline exposure elicits splenotoxic response, especially the tumorigenic response, are not well-understood. Earlier, we have shown that aniline-induced oxidative stress is associated with increased oxidative DNA damage in rat spleen. The base excision repair (BER) pathway is the major mechanism for the repair of oxidative DNA base lesions, and we have shown an up-regulation of 8-oxoguanine glycosylase 1 (OGG1), a specific DNA glycosylase involved in the removal of 8-hydroxy-2′-deoxyguanosine (8-OHdG) adducts, following aniline exposure. Nei-like DNA glycosylases (NEIL1/2) belong to a family of BER proteins that are distinct from other DNA glycosylases, including OGG1. However, contribution of NEIL1/2 in the repair of aniline-induced oxidative DNA damage in the spleen is not known. This study was, therefore, focused on evaluating if NEILs also contribute to the repair of oxidative DNA lesions in the spleen following aniline exposure. To achieve that, male SD rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. The BER activity of NEIL1/2 was assayed using a bubble structure substrate containing 5-OHU (preferred substrates for NEIL1 and NEIL2) and by quantitating the cleavage products. Aniline treatment led to a 1.25-fold increase in the NEIL1/2-associated BER activity in the nuclear extracts of spleen compared to the controls. Real-time PCR analysis for NEIL1 and NEIL2 mRNA expression in the spleen revealed 2.7- and 3.9-fold increases, respectively, in aniline-treated rats compared to controls. Likewise, Western blot analysis showed that protein expression of NEIL1 and NEIL2 in the nuclear extract of spleens from aniline-treated rats was 2.0- and 3.8-fold higher than controls, respectively. Aniline treatment also led to stronger immunoreactivity for NEIL1 and NEIL2 in the spleens, confined to the red pulp areas. These studies, thus, show that aniline-induced oxidative stress is associated with an induction of NEIL1/2. The increased NIELs-mediated BER activity is another indication of aniline-induced oxidative damage in the spleen and could constitute another important mechanism of removal of oxidative DNA lesions, especially in transcribed DNA following aniline insult. PMID:21145906

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

PubMed

Jones, D A; Prior, S L; Barry, J D; Caplin, S; Baxter, J N; Stephens, J W

2014-12-01

In the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes. Visceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage. No significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (P<0.05). Lower MDA concentration and longer telomere length were seen in subjects with diabetes compared to those without (P<0.05). DNA damage, analysed via Comet assay, was significantly lower in subjects with diabetes compared to those without (P<0.05). A paradoxical decrease in oxidative stress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genotoxicity and oxidative stress in chromium-exposed tannery workers in North India.

PubMed

Ambreen, Khushboo; Khan, Faizan Haider; Bhadauria, Smrati; Kumar, Sudhir

2014-06-01

Trivalent chromium (Cr) is an environmental contaminant, which is extensively used in tanning industries throughout the world and causes various forms of health hazards in tannery workers. Therefore, a cross-sectional study design was used to evaluate the DNA damage and oxidative stress condition in tannery workers exposed to Cr in North India. The study population comprised 100 male tanners in the exposed group and 100 healthy males (no history of Cr exposure) in the comparable control group. Baseline characteristics including age, smoking, alcohol consumption habits and duration of exposure were recorded via interviewing the subjects. Blood Cr level (measured by atomic absorption spectrophotometry), DNA damage (measured by comet assay) and oxidative stress parameters (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) were estimated in both the groups. As a result of statistical analysis, exposed group showed significantly higher level of Cr (p < 0.0001), DNA damage (p < 0.0001), MDA (p < 0.0001), SOD (p < 0.05) and lower level of GSH (p < 0.001) when compared with controls. Smoking, alcohol consumption habits and age had no significant effect (p > 0.05) on DNA damage and oxidative stress parameters in both the groups. In simple and multiple correlation analysis, DNA damage and oxidative stress parameters showed significant correlation with Cr level and duration of exposure in exposed group. The findings of the present study revealed that chronic occupational exposure to trivalent Cr may cause DNA damage and oxidative stress in tannery workers. © The Author(s) 2012.

Chronic predation risk reduces escape speed by increasing oxidative damage: a deadly cost of an adaptive antipredator response.

PubMed

Janssens, Lizanne; Stoks, Robby

2014-01-01

Prey organisms evolved a multitude of plastic responses to avoid being eaten by predators. Besides the evolution of plastic morphological responses to escape predation, prey also evolved a set of physiological stress responses to avoid dying because of chronic predator stress per se due to disruption of cellular homeostasis. As physiological stress theory predicts increased energy consumption and the inhibition of essential nonemergency body functions, we tested whether chronic predation risk may increase oxidative damage thereby generating negative effects on escape performance. Specifically, we evaluated whether predation risk reduces escape swimming speed in damselfly larvae and whether this operates through stress-associated increases in oxidative damage. Counterintuitively and in contrast with many empirical studies, chronic predation risk decreased escape performance. This is however entirely consistent with the expectation of it being a long-term cost of responding to predation risk (e.g. by increasing respiration or upregulating the stress protein levels). The decreased swimming speed could be explained by an increased oxidative damage to proteins, thereby providing one of the poorly studied ecological links between oxidative damage and whole-animal performance. This likely widespread, understudied cost of chronic predation risk may provide an important pathway of non-consumptive predator effects on prey population dynamics. Moreover, it could play an evolutionary role by acting as a selective force causing prey organisms to adjust the magnitude of the physiological stress response and should be considered when evaluating life history trade-offs thought to be mediated by oxidative damage.

Chronic Predation Risk Reduces Escape Speed by Increasing Oxidative Damage: A Deadly Cost of an Adaptive Antipredator Response

PubMed Central

Janssens, Lizanne; Stoks, Robby

2014-01-01

Prey organisms evolved a multitude of plastic responses to avoid being eaten by predators. Besides the evolution of plastic morphological responses to escape predation, prey also evolved a set of physiological stress responses to avoid dying because of chronic predator stress per se due to disruption of cellular homeostasis. As physiological stress theory predicts increased energy consumption and the inhibition of essential nonemergency body functions, we tested whether chronic predation risk may increase oxidative damage thereby generating negative effects on escape performance. Specifically, we evaluated whether predation risk reduces escape swimming speed in damselfly larvae and whether this operates through stress-associated increases in oxidative damage. Counterintuitively and in contrast with many empirical studies, chronic predation risk decreased escape performance. This is however entirely consistent with the expectation of it being a long-term cost of responding to predation risk (e.g. by increasing respiration or upregulating the stress protein levels). The decreased swimming speed could be explained by an increased oxidative damage to proteins, thereby providing one of the poorly studied ecological links between oxidative damage and whole-animal performance. This likely widespread, understudied cost of chronic predation risk may provide an important pathway of non-consumptive predator effects on prey population dynamics. Moreover, it could play an evolutionary role by acting as a selective force causing prey organisms to adjust the magnitude of the physiological stress response and should be considered when evaluating life history trade-offs thought to be mediated by oxidative damage. PMID:24968142

Phototherapy causes DNA damage in peripheral mononuclear leukocytes in term infants.

PubMed

Aycicek, Ali; Kocyigit, Abdurrahim; Erel, Ozcan; Senturk, Hakan

2008-01-01

Our aim was to determine whether endogenous mononuclear leukocyte DNA strand is a target of phototherapy. The study included 65 term infants aged between 3-10 days that had been exposed to intensive (n = 23) or conventional (n = 23) phototherapy for at least 48 hours due to neonatal jaundice, and a control group (n = 19). DNA damage was assayed by single-cell alkaline gel electrophoresis (comet assay). Plasma total antioxidant capacity and total oxidant status levels were also measured, and correlation between DNA damage and oxidative stress was investigated. Mean values of DNA damage scores in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p < 0.001). Mean values and standard deviation were 32 (9), 28 (9), 21 (7) arbitrary unit, respectively. Total oxidant status levels in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p = 0.005). Mean (standard deviation) values were 18.1 (4.2), 16.9 (4.4), 13.5 (4.2) micromol H2O2 equivalent/L, respectively. Similarly, oxidative stress index levels in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p = 0.041). Plasma total antioxidant capacity and total bilirubin levels did not differ between the groups (p > 0.05). There were no significant correlations between DNA damage scores and bilirubin, total oxidant status and oxidative stress levels in either phototherapy group (p > 0.05). Both conventional phototherapy and intensive phototherapy cause endogenous mononuclear leukocyte DNA damage in jaundiced term infants.

Application of the CometChip platform to assess DNA damage in field-collected blood samples from turtles.

PubMed

Sykora, Peter; Chiari, Ylenia; Heaton, Andrew; Moreno, Nickolas; Glaberman, Scott; Sobol, Robert W

2018-05-01

DNA damage has been linked to genomic instability and the progressive breakdown of cellular and organismal homeostasis, leading to the onset of disease and reduced longevity. Insults to DNA from endogenous sources include base deamination, base hydrolysis, base alkylation, and metabolism-induced oxidative damage that can lead to single-strand and double-strand DNA breaks. Alternatively, exposure to environmental pollutants, radiation or ultra-violet light, can also contribute to exogenously derived DNA damage. We previously validated a novel, high through-put approach to measure levels of DNA damage in cultured mammalian cells. This new CometChip Platform builds on the classical single cell gel electrophoresis or comet methodology used extensively in environmental toxicology and molecular biology. We asked whether the CometChip Platform could be used to measure DNA damage in samples derived from environmental field studies. To this end, we determined that nucleated erythrocytes from multiple species of turtle could be successfully evaluated in the CometChip Platform to quantify levels of DNA damage. In total, we compared levels of DNA damage in 40 animals from two species: the box turtle (Terrapene carolina) and the red-eared slider (Trachemys scripta elegans). Endogenous levels of DNA damage were identical between the two species, yet we did discover some sex-linked differences and changes in DNA damage accumulation. Based on these results, we confirm that the CometChip Platform allows for the measurement of DNA damage in a large number of samples quickly and accurately, and is particularly adaptable to environmental studies using field-collected samples. Environ. Mol. Mutagen. 59:322-333, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS.

PubMed

Drechsel, Derek A; Estévez, Alvaro G; Barbeito, Luis; Beckman, Joseph S

2012-11-01

Oxidative damage is a common and early feature of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders. Dr. Mark Smith and his colleagues have built the case for oxidative stress being a primary progenitor rather than a secondary end-stage epiphenomenon of neurodegeneration. They proposed that reactive oxygen species contribute to the "age-related cascade of neurodegeneration," whereby accumulative oxidative damage with age promotes other characteristic pathological changes in afflicted brain regions, including protein aggregation, metabolic deficiencies, and inflammation. Nitric oxide (NO) likely plays a critical role in this age-related cascade. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through stimulating cyclic GMP synthesis. However, the same physiological concentrations of NO, relevant in cellular signaling, may also initiate and amplify oxidative damage by diffusion-limited reactions with superoxide (O(2)(•-)) to produce peroxynitrite (ONOO(-)). This is perhaps best illustrated in ALS where physiological levels of NO promote survival of motor neurons, but the same concentrations can stimulate motor neuron apoptosis and glial cell activation under pathological conditions. While these changes represent a complex mechanism involving multiple cell types in the pathogenesis of ALS, they also reveal general processes underlying neurodegeneration.

Formation of Clustered DNA Damage after High-LET Irradiation: A Review

NASA Technical Reports Server (NTRS)

Hada, Megumi; Georgakilas, Alexandros G.

2008-01-01

Radiation can cause as well as cure cancer. The risk of developing radiation-induced cancer has traditionally been estimated from cancer incidence among survivors of the atomic bombs in Hiroshima and Nagasaki. These data provide the best estimate of human cancer risk over the dose range for low linear energy transfer (LET) radiations, such as X- or gamma-rays. The situation of estimating the real biological effects becomes even more difficult in the case of high LET particles encountered in space or as the result of domestic exposure to particles from radon gas emitters or other radioactive emitters like uranium-238. Complex DNA damage, i.e., the signature of high-LET radiations comprises by closely spaced DNA lesions forming a cluster of DNA damage. The two basic groups of complex DNA damage are double strand breaks (DSBs) and non-DSB oxidative clustered DNA lesions (OCDL). Theoretical analysis and experimental evidence suggest there is increased complexity and severity of complex DNA damage with increasing LET (linear energy transfer) and a high mutagenic or carcinogenic potential. Data available on the formation of clustered DNA damage (DSBs and OCDL) by high-LET radiations are often controversial suggesting a variable response to dose and type of radiation. The chemical nature and cellular repair mechanisms of complex DNA damage have been much less characterized than those of isolated DNA lesions like an oxidized base or a single strand break especially in the case of high-LET radiation. This review will focus on the induction of clustered DNA damage by high-LET radiations presenting the earlier and recent relative data.

Regulatory mechanisms of thiol-based redox sensors: lessons learned from structural studies on prokaryotic redox sensors.

PubMed

Lee, Sang Jae; Kim, Dong-Gyun; Lee, Kyu-Yeon; Koo, Ji Sung; Lee, Bong-Jin

2018-05-17

Oxidative stresses, such as reactive oxygen species, reactive electrophilic species, reactive nitrogen species, and reactive chlorine species, can damage cellular components, leading to cellular malfunction and death. In response to oxidative stress, bacteria have evolved redox-responsive sensors that enable them to simultaneously monitor and eradicate potential oxidative stress. Specifically, redox-sensing transcription regulators react to oxidative stress by means of modifying the thiol groups of cysteine residues, functioning as part of an efficient survival mechanism for many bacteria. In general, oxidative molecules can induce changes in the three-dimensional structures of redox sensors, which, in turn, affects the transcription of specific genes in detoxification pathways and defense mechanisms. Moreover, pathogenic bacteria utilize these redox sensors for adaptation and to evade subsequent oxidative attacks from host immune defense. For this reason, the redox sensors of pathogenic bacteria are potential antibiotic targets. Understanding the regulatory mechanisms of thiol-based redox sensors in bacteria will provide insight and knowledge into the discovery of new antibiotics.

No evidence of oxidative stress after a triathlon race in highly trained competitors.

PubMed

Margaritis, I; Tessier, F; Richard, M J; Marconnet, P

1997-04-01

Long distance triathlons, due to the large amounts of oxygen uptake they cause, may lead to the generation of reactive oxygen species, and consequently to oxidative stress and damage. We sought to verify this hypothesis. Twelve of the 18 male triathletes who participated in the study took part in a long distance triathlon, the others did not. The prerace blood samples were drawn 48 h before the race and repeatedly until the fourth day of recovery. The myoglobin concentrations increased immediately after the race. The concentrations of methemoglobin, disulfide glutathione (GSSG), and thiobarbituric reactive substances did not significantly change after the race. Although the race induced an inflammatory response, evidenced by the variations in neopterin concentrations and leukocyte counts, there was no consecutive oxidative stress. The basal GSH values were correlated significantly with cycling training volume (r = 0.55) and VO2max (r = 0.53). Muscle damage can occur without evidence of oxidative stress or oxidative damage. We conclude that the magnitude of the antioxidant defense system enhancement depends on training loads. Because of their training status, the triathletes did not suffer from oxidative damage after they finished the long distance triathlon race.

Systemic inflammation and oxidative stress post-lung resection: Effect of pretreatment with N-acetylcysteine.

PubMed

Bastin, Anthony J; Davies, Nathan; Lim, Eric; Quinlan, Greg J; Griffiths, Mark J

2016-01-01

N-acetylcysteine has been used to treat a variety of lung diseases, where is it thought to have an antioxidant effect. In a randomized placebo-controlled double-blind study, the effect of N-acetylcysteine on systemic inflammation and oxidative damage was examined in patients undergoing lung resection, a human model of acute lung injury. Eligible adults were randomized to receive preoperative infusion of N-acetylcysteine (240 mg/kg over 12 h) or placebo. Plasma thiols, interleukin-6, 8-isoprostane, ischaemia-modified albumin, red blood cell glutathione and exhaled breath condensate pH were measured pre- and post-operatively as markers of local and systemic inflammation and oxidative stress. Patients undergoing lung resection and one-lung ventilation exhibited significant postoperative inflammation and oxidative damage. Postoperative plasma thiol concentration was significantly higher in the N-acetylcysteine-treated group. However, there was no significant difference in any of the measured biomarkers of inflammation or oxidative damage, or in clinical outcomes, between N-acetylcysteine and placebo groups. Preoperative administration of N-acetylcysteine did not attenuate postoperative systemic or pulmonary inflammation or oxidative damage after lung resection. NCT00655928 at ClinicalTrials.gov. © 2015 Asian Pacific Society of Respirology.

Respiratory terminal oxidases alleviate photo-oxidative damage in photosystem I during repetitive short-pulse illumination in Synechocystis sp. PCC 6803.

PubMed

Shimakawa, Ginga; Miyake, Chikahiro

2018-03-08

Oxygenic phototrophs are vulnerable to damage by reactive oxygen species (ROS) that are produced in photosystem I (PSI) by excess photon energy over the demand of photosynthetic CO 2 assimilation. In plant leaves, repetitive short-pulse (rSP) illumination produces ROS to inactivate PSI. The production of ROS is alleviated by oxidation of the reaction center chlorophyll in PSI, P700, during the illumination with the short-pulse light, which is supported by flavodiiron protein (FLV). In this study, we found that in the cyanobacterium Synechocystis sp. PCC 6803 P700 was oxidized and PSI was not inactivated during rSP illumination even in the absence of FLV. Conversely, the mutant deficient in respiratory terminal oxidases was impaired in P700 oxidation during the illumination with the short-pulse light to suffer from photo-oxidative damage in PSI. Interestingly, the other cyanobacterium Synechococcus sp. PCC 7002 could not oxidize P700 without FLV during rSP illumination. These data indicate that respiratory terminal oxidases are critical to protect PSI from ROS damage during rSP illumination in Synechocystis sp. PCC 6803 but not Synechococcus sp. PCC 7002.

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

DTIC Science & Technology

2010-01-01

mice: protective effect of alpha - lipoic acid . Behav Brain Res 2007b; 177(1): 7-14. [8] Manda K, Ueno M, Anzai K. Melatonin mitigates oxidative...Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha - lipoic acid . Behav Brain Res 2008b...1977; 171(1): 39-50. [6] Manda K, Ueno M, Moritake T, Anzai K. - Lipoic acid attenuates x-irradiation-induced oxidative stress in mice. Cell Biol

Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

PubMed

Okusaga, Olaoluwa O

2014-08-01

Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

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

PubMed

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

2016-01-01

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

Increased total DNA damage and oxidative stress in brain are associated with decreased longevity in high sucrose diet fed WNIN/Gr-Ob obese rats.

PubMed

Potukuchi, Aruna; Addepally, Uma; Sindhu, Kirankumar; Manchala, Raghunath

2017-06-01

Obesity and Type 2 Diabetes (T2D) are chronic nutrient-related disorders that occur together and pose a grave burden to society. They are among the most common causes of ageing and death. Obesity and T2D per se accelerate ageing albeit the underlying mechanisms are unclear yet. Also, it is not clear whether or not superimposing T2D on obesity accelerates ageing. Present study validated the hypothesis, 'super-imposing T2D on obesity accelerates ageing' in WNIN/Gr-Ob, the impaired glucose tolerant, obese rat as the model and evaluated probable underlying mechanisms. To estimate the survival analysis of WNIN/Gr-Ob rats induced with T2D. To determine the extent of DNA damage and oxidative stress in the brain, the master controller of the body, in WNIN/Gr-Ob rats with/without high sucrose induced T2D/aggravation of insulin resistance (IR) after 3 and 6 months of feeding. T2D was induced/IR was aggravated by feeding high sucrose diet (HSD) to 9-10 weeks old, male WNIN/Gr-Ob rats. Survival percentage was determined statistically by Kaplan-Meier estimator. Neuronal DNA damage was quantified by the Comet assay while the oxidative stress and antioxidant status were evaluated from the levels of malonaldialdehyde, reduced glutathione, and superoxide dismutase (SOD) activity. HSD feeding decreased longevity of WNIN/Gr-Ob rats and was associated with significantly higher total neuronal DNA damage after three months of feeding but not later. In line with this was the increased neuronal oxidative stress (lipid peroxidation) and decreased antioxidant status (reduced glutathione and SOD activity) in HSD than Starch-based diet (SBD) fed rats. The results suggest that HSD feeding decreased the longevity of WNIN/Gr-Ob obese rats probably by increasing oxidative stress and aggravating IR, a condition that precedes T2D.

The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial.

PubMed

Mitjavila, Maria Teresa; Fandos, Marta; Salas-Salvadó, Jordi; Covas, María-Isabel; Borrego, Silvia; Estruch, Ramón; Lamuela-Raventós, Rosa; Corella, Dolores; Martínez-Gonzalez, Miguel Ángel; Sánchez, Julia M; Bulló, Mónica; Fitó, Montserrat; Tormos, Carmen; Cerdá, Concha; Casillas, Rosario; Moreno, Juan José; Iradi, Antonio; Zaragoza, Cristóbal; Chaves, Javier; Sáez, Guillermo T

2013-04-01

Metabolic syndrome (MetS), in which a non-classic feature is an increase in systemic oxidative biomarkers, presents a high risk of diabetes and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet) is associated with a reduced risk of MetS. However, the effect of the MedDiet on biomarkers for oxidative damage has not been assessed in MetS individuals. We have investigated the effect of the MedDiet on systemic oxidative biomarkers in MetS individuals. Randomized, controlled, parallel clinical trial in which 110 female with MetS, aged 55-80, were recruited into a large trial (PREDIMED Study) to test the efficacy of the traditional MedDiet on the primary prevention of CVD. Participants were assigned to a low-fat diet or two traditional MedDiets (MedDiet + virgin olive oil or MedDiet + nuts). Both MedDiet group participants received nutritional education and either free extra virgin olive oil for all the family (1 L/week), or free nuts (30 g/day). Diets were ad libitum. Changes in urine levels of F2-Isoprostane (F2-IP) and the DNA damage base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) were evaluated at 1-year trial. After 1-year urinary F2-IP decreased in all groups, the decrease in MedDiet groups reaching a borderline significance versus that of the Control group. Urinary 8-oxo-dG was also reduced in all groups, with a higher decrease in both MedDiet groups versus the Control one (P < 0.001). MedDiet reduces oxidative damage to lipids and DNA in MetS individuals. Data from this study provide evidence to recommend the traditional MedDiet as a useful tool in the MetS management. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Experimental Analysis of Proton-Induced Displacement and Ionization Damage Using Gate-Controlled Lateral PNP Bipolar Transistors

NASA Technical Reports Server (NTRS)

Ball, D. R.; Schrimpf, R. D.; Barnaby, H. J.

2006-01-01

The electrical characteristics of proton-irradiated bipolar transistors are affected by ionization damage to the insulating oxide and displacement damage to the semiconductor bulk. While both types of damage degrade the transistor, it is important to understand the mechanisms individually and to be able to analyze them separately. In this paper, a method for analyzing the effects of ionization and displacement damage using gate-controlled lateral PNP bipolar junction transistors is described. This technique allows the effects of oxide charge, surface recombination velocity, and bulk traps to be measured independently.

Evaluation of Both Free Radical Scavenging Capacity and Antioxidative Damage Effect of Polydatin.

PubMed

Jin, Ju; Li, Yan; Zhang, Xiuli; Chen, Tongsheng; Wang, Yifei; Wang, Zhiping

Cellular damage such as oxidation and lipid peroxidation, and DNA damage induced by free-radicals like reactive oxygen species, has been implicated in several diseases. Radicals generated by 2,2-azobis (2-amidino-propane) dihydrochloride (AAPH) are similar to physiologically active ones. In this study we found that polydatin, a resveratrol natural precursor derived from many sources, has the capacity of free radical scavenging and antioxidative damage. Using free radical scavenging assays, the IC50 values of polydatin were 19.25 and 5.29 μg/ml with the DPPH and the ABTS assay, respectively, and 0.125 mg ferrous sulfate/1 mg polydatin with the FRAP assay. With the AAPH-induced oxidative injury cell model assay, polydatin showed a strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicate that the antioxidant properties of polydatin have great potential for use as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetics and pharmaceutical preparations for the treatment of oxidative diseases.

DNA damage in children exposed to secondhand cigarette smoke and its association with oxidative stress.

PubMed

Shermatov, Kabil; Zeyrek, Dost; Yildirim, Faruk; Kilic, Mehmet; Cebi, Nazime; Kocyigit, Abdurrahim

2012-12-01

To compare oxidative status, total antioxidant capacity and values of DNA damage in peripheral blood lymphocytes in children exposed to secondhand cigarette smoke with healthy controls. Analytical, Observational. 54 children without any chronic diseases, attending the healthy child monitoring polyclinic. These comprised 27 children who had been exposed to passive cigarette smoke and 27 children who had not been exposed to cigarette smoke. Urine cotinine levels by the chemiluminescent technique; DNA damage by alkaline comet assay; and total oxidant status (TOS) using a novel automated measurement method. The mean urine cotinine, TOS, Oxidative Stress Index (OSI) and DNA damage values of the group exposed to cigarette smoke were determined to be at significantly higher level compared to the group not exposed to cigarette smoke (P<0.001). No statistically significant difference was determined in the TAS level between the two groups (P=0.1) The results showed that TOS levels, OSI index and DNA damage in peripheral blood lymphocytes were significantly higher in children exposed to secondhand cigarette smoke than in those not exposed to secondhand cigarette smoke.

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

PubMed Central

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro

2018-01-01

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms. PMID:29748512

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina.

PubMed

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro; Ohira, Akihiro

2018-05-10

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O -glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut ( Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

PubMed Central

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

Neutral beam and ICP etching of HKMG MOS capacitors: Observations and a plasma-induced damage model

NASA Astrophysics Data System (ADS)

Kuo, Tai-Chen; Shih, Tzu-Lang; Su, Yin-Hsien; Lee, Wen-Hsi; Current, Michael Ira; Samukawa, Seiji

2018-04-01

In this study, TiN/HfO2/Si metal-oxide-semiconductor (MOS) capacitors were etched by a neutral beam etching technique under two contrasting conditions. The configurations of neutral beam etching technique were specially designed to demonstrate a "damage-free" condition or to approximate "reactive-ion-etching-like" conditions to verify the effect of plasma-induced damage on electrical characteristics of MOS capacitors. The results show that by neutral beam etching (NBE), the interface state density (Dit) and the oxide trapped charge (Qot) were lower than routine plasma etching. Furthermore, the decrease in capacitor size does not lead to an increase in leakage current density, indicating less plasma induced side-wall damage. We present a plasma-induced gate stack damage model which we demonstrate by using these two different etching configurations. These results show that NBE is effective in preventing plasma-induced damage at the high-k/Si interface and on the high-k oxide sidewall and thus improve the electrical performance of the gate structure.

Oxidative Stress and Antioxidant System in Periodontitis

PubMed Central

Wang, Yue; Andrukhov, Oleh; Rausch-Fan, Xiaohui

2017-01-01

Periodontitis is a common inflammatory disease, which is initiated by bacterial infection and subsequently progressed by aberrant host response. It can result in the destruction of teeth supporting tissues and have an influence on systemic health. When periodontitis occurs, reactive oxygen species, which are overproduced mostly by hyperactive neutrophils, could not be balanced by antioxidant defense system and cause tissues damage. This is characterized by increased metabolites of lipid peroxidation, DNA damage and protein damage. Local and systemic activities of antioxidants can also be influenced by periodontitis. Total antioxidant capacity, total oxidant status and oxidative stress index have been used to evaluate the oxidative stress associated with periodontitis. Studies have confirmed that inflammatory response in periodontitis is associated with an increased local and systemic oxidative stress and compromised antioxidant capacity. Our review focuses on increased oxidative stress in periodontal disease, specifically, on the relationship between the local and systemic biomarkers of oxidative stress and periodontitis and their association with the pathogenesis of periodontitis. Also, the relationship between periodontitis and systemic inflammation, and the effects of periodontal therapy on oxidative stress parameters will be discussed. PMID:29180965

Metal accumulation and oxidative stress biomarkers in octopus (Octopus vulgaris) from Northwest Atlantic.

PubMed

Semedo, Miguel; Reis-Henriques, Maria Armanda; Rey-Salgueiro, Ledicia; Oliveira, Marta; Delerue-Matos, Cristina; Morais, Simone; Ferreira, Marta

2012-09-01

Metals are ubiquitous in the environment and accumulate in aquatic organisms and are known for their ability to enhance the production of reactive oxygen species (ROS). In aquatic species, oxidative stress mechanisms have been studied by measuring antioxidant enzyme activities and oxidative damages in tissues. The aim of this study was to apply and validate a set of oxidative stress biomarkers and correlate responses with metal contents in tissues of common octopus (Octopus vulgaris). Antioxidant enzyme activity (catalase--CAT, superoxide dismutase--SOD and glutathione S-transferases--GST), oxidative damages (lipid peroxidation--LPO and protein carbonyl content--PCO) and metal content (Cu, Zn, Pb, Cd and As) in the digestive gland and arm of octopus, collected in the NW Portuguese coast in different periods, were assessed after capture and after 14 days in captivity. CAT and SOD activities were highly responsive to fluctuations in metal concentrations and able to reduce oxidative damage, LPO and PCO in the digestive gland. CAT activity was also positively correlated with SOD and GST activities, which emphasizes that the three enzymes respond in a coordinated way to metal induced oxidative stress. Our results validate the use of oxidative stress biomarkers to assess metal pollution effects in this ecological and commercial relevant species. Moreover, octopus seems to have the ability to control oxidative damage by triggering an antioxidant enzyme coordinated response in the digestive gland. Copyright © 2012 Elsevier B.V. All rights reserved.

Potential role of punicalagin against oxidative stress induced testicular damage.

PubMed

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

Potential role of punicalagin against oxidative stress induced testicular damage

PubMed Central

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism

PubMed Central

Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

2016-01-01

Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. Methods: The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2- scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays. Results: Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2- scavenging, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form. PMID:27478791

Ischemic and oxidative damage to the hypothalamus may be responsible for heat stroke.

PubMed

Chen, Sheng-Hsien; Lin, Mao-Tsun; Chang, Ching-Ping

2013-03-01

The hypothalamus may be involved in regulating homeostasis, motivation, and emotional behavior by controlling autonomic and endocrine activity. The hypothalamus communicates input from the thalamus to the pituitary gland, reticular activating substance, limbic system, and neocortex. This allows the output of pituitary hormones to respond to changes in autonomic nervous system activity. Environmental heat stress increases cutaneous blood flow and metabolism, and progressively decreases splanchnic blood flow. Severe heat exposure also decreases mean arterial pressure (MAP), increases intracranial pressure (ICP), and decreases cerebral perfusion pressure (CPP = MAP - ICP), all of which lead to cerebral ischemia and hypoxia. Compared with normothermic controls, rodents with heatstroke have higher hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol) markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), proinflammatory cytokines (e.g., interleukin-1β and tumor necrosis factor-α), inducible nitric oxide synthase-dependent nitric oxide, and an indicator for the accumulation of polymorphonuclear leukocytes (e.g., myeloperoxidase activity), as well as neuronal damage (e.g., apoptosis, necrosis, and autophagy) after heatstroke. Hypothalamic values of antioxidant defenses (e.g., glutathione peroxidase and glutathione reductase), however, are lower. The ischemic, hypoxic, and oxidative damage to the hypothalamus during heatstroke may cause multiple organ dysfunction or failure through hypothalamic-pituitary-adrenal axis mechanisms. Finding the link between the signaling and heatstroke-induced hypothalamic oxidative and ischemic damage might allow us to clinically attenuate heatstroke. In particular, free radical scavengers, heat shock protein-70 inducers, hypervolemic hemodilution, inducible nitric oxide synthase inhibitors, progenitor stem cells, flutamide, estrogen, interleukin-1 receptor antagonists, glucocorticoid, activated protein C, and baicalin mitigate preclinical heatstroke levels.

Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups

PubMed Central

Vázquez-Medina, José Pablo; Crocker, Daniel E.; Forman, Henry Jay; Ortiz, Rudy M.

2010-01-01

Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin–angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2–3 weeks post-weaning) and late (7–8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT1), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT1, a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40–60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences. PMID:20581282

Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups.

PubMed

Vázquez-Medina, José Pablo; Crocker, Daniel E; Forman, Henry Jay; Ortiz, Rudy M

2010-07-15

Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences.

Nondestructive Evaluation (NDE) for Characterizing Oxidation Damage in Cracked Reinforced Carbon-Carbon

NASA Technical Reports Server (NTRS)

Roth, Don J.; Jacobson, Nathan S.; Rauser, Richard W.; Wincheski, Russell A.; Walker, James L.; Cosgriff, Laura A.

2010-01-01

In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter's thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using nondestructive evaluation (NDE) methods. These specimens were heat treated in air at 1143 C and 1200 C to create cavities in the carbon substrate underneath the coating as oxygen reacted with the carbon and resulted in its consumption. The cavities varied in diameter from approximately 1 to 3mm. Single-sided NDE methods were used because they might be practical for on-wing inspection, while X-ray micro-computed tomography (CT) was used to measure cavity sizes in order to validate oxidation models under development for carbon-carbon materials. An RCC sample having a naturally cracked coating and subsequent oxidation damage was also studied with X-ray micro-CT. This effort is a follow-on study to one that characterized NDE methods for assessing oxidation damage in an RCC sample with drilled holes in the coating.

Nondestructive Evaluation (NDE) for Characterizing Oxidation Damage in Cracked Reinforced Carbon-Carbon (RCC)

NASA Technical Reports Server (NTRS)

Roth, Don J.; Rauser, Richard W.; Jacobson, Nathan S.; Wincheski, Russell A.; Walker, James L.; Cosgriff, Laura A.

2009-01-01

In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter's thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using nondestructive evaluation (NDE) methods. These specimens were heat treated in air at 1143 and 1200 C to create cavities in the carbon substrate underneath the coating as oxygen reacted with the carbon and resulted in its consumption. The cavities varied in diameter from approximately 1 to 3 mm. Single-sided NDE methods were used since they might be practical for on-wing inspection, while x-ray micro-computed tomography (CT) was used to measure cavity sizes in order to validate oxidation models under development for carbon-carbon materials. An RCC sample having a naturally-cracked coating and subsequent oxidation damage was also studied with x-ray micro-CT. This effort is a follow-on study to one that characterized NDE methods for assessing oxidation damage in an RCC sample with drilled holes in the coating.

Oxidative damage in gills and liver in Nile tilapia (Oreochromis niloticus) exposed to diazinon.

PubMed

Toledo-Ibarra, G A; Díaz Resendiz, K J G; Ventura-Ramón, G H; González-Jaime, F; Vega-López, A; Becerril-Villanueva, E; Pavón, L; Girón-Pérez, M I

2016-10-01

Agricultural activity demands the use of pesticides for plague control and extermination. In that matter, diazinon is one of the most widely used organophosphorus pesticides (OPs). Despite its benefits, the use of OPs in agricultural activities can also have negative effects since the excessive use of these substances can represent a major contamination problem for water bodies and organisms that inhabit them. The aim of this paper was to evaluate oxidative damage in lipids and proteins of Nile tilapia (Oreochromis niloticus) exposed acutely to diazinon (0.97, 1.95 and 3.95ppm) for 12 or 24h. The evaluation of oxidative damage was determined by quantifying lipid hydroperoxides (Fox method) and oxidized proteins (DNPH method). The data from this study suggest that diazinon induces a concentration-dependent oxidative damage in proteins, but not lipids, of the liver and gills of Nile tilapia. Furthermore, the treatment leads to a decrease in the concentration of total proteins, which can have serious consequences in cell physiology and fish development. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins.

PubMed

Park, Su-Jung; Ciccone, Samantha L M; Beck, Brian D; Hwang, Byounghoon; Freie, Brian; Clapp, D Wade; Lee, Suk-Hee

2004-07-16

Fanconi anemia (FANC) is a heterogeneous genetic disorder characterized by a hypersensitivity to DNA-damaging agents, chromosomal instability, and defective DNA repair. Eight FANC genes have been identified so far, and five of them (FANCA, -C, -E, -F, and -G) assemble in a multinuclear complex and function at least in part in a complex to activate FANCD2 by monoubiquitination. Here we show that FANCA and FANCG are redox-sensitive proteins that are multimerized and/or form a nuclear complex in response to oxidative stress/damage. Both FANCA and FANCG proteins exist as monomers under non-oxidizing conditions, whereas they become multimers following H2O2 treatment. Treatment of cells with oxidizing agent not only triggers the multimeric complex of FANCA and FANCG in vivo but also induces the interaction between FANCA and FANCG. N-Ethylmaleimide treatment abolishes multimerization and interaction of FANCA and FANCG in vitro. Taken together, our results lead us to conclude that FANCA and FANCG uniquely respond to oxidative damage by forming complex(es) via intermolecular disulfide linkage(s), which may be crucial in forming such complexes and in determining their function.

Does oxidative stress shorten telomeres?

PubMed

Boonekamp, Jelle J; Bauch, Christina; Mulder, Ellis; Verhulst, Simon

2017-05-01

Oxidative stress shortens telomeres in cell culture, but whether oxidative stress explains variation in telomere shortening in vivo at physiological oxidative stress levels is not well known. We therefore tested for correlations between six oxidative stress markers and telomere attrition in nestling birds (jackdaws Corvus monedula ) that show a high rate of telomere attrition in early life. Telomere attrition was measured between ages 5 and 30 days, and was highly variable (average telomere loss: 323 bp, CV = 45%). Oxidative stress markers were measured in blood at age 20 days and included markers of oxidative damage (TBARS, dROMs and GSSG) and markers of antioxidant protection (GSH, redox state, uric acid). Variation in telomere attrition was not significantly related to these oxidative stress markers (| r | ≤ 0.08, n = 87). This finding raises the question whether oxidative stress accelerates telomere attrition in vivo The accumulation of telomere attrition over time depends both on the number of cell divisions and on the number of base pairs lost per DNA replication and, based on our findings, we suggest that in a growing animal cell proliferation, dynamics may be more important for explaining variation in telomere attrition than oxidative stress. © 2017 The Author(s).

Graphene production by laser shot on graphene oxide: An ab initio prediction

NASA Astrophysics Data System (ADS)

Zhang, Hong; Miyamoto, Yoshiyuki

2012-01-01

By performing the first-principles simulation of electron-ion dynamics based on the time-dependent density-functional theory, we propose a way to produce graphene from graphene oxides by means of the laser-induced reduction without using chemical species. Epoxy and hydroxyl groups on graphene sheets can be completely removed upon irradiation with femtosecond laser without damaging the graphene sheet. By comparing the simulated results with different pulse shapes and intensities, optimum conditions of the femtosecond laser for reduction of graphene oxide were determined. The current works will be useful for further experimental researches.

Induction and repair of DNA damage measured by the comet assay in human T lymphocytes separated by immunomagnetic cell sorting.

PubMed

Bausinger, Julia; Speit, Günter

2014-11-01

The comet assay is widely used in human biomonitoring to measure DNA damage in whole blood or isolated peripheral blood mononuclear cells (PBMC) as a marker of exposure to genotoxic agents. Cytogenetic assays with phytohemagglutinin (PHA)-stimulated cultured T lymphocytes are also frequently performed in human biomonitoring. Cytogenetic effects (micronuclei, chromosome aberrations, sister chromatid exchanges) may be induced in vivo but also occur ex vivo during the cultivation of lymphocytes as a consequence of DNA damage present in lymphocytes at the time of sampling. To better understand whether DNA damage measured by the comet assay in PBMC is representative for DNA damage in T cells, we comparatively investigated DNA damage and its repair in PBMC and T cells obtained by immunomagnetic cell sorting. PBMC cultures and T cell cultures were exposed to mutagens with different modes of genotoxic action and DNA damage was measured by the comet assay after the end of a 2h exposure and after 18h post-incubation. The mutagens tested were methyl methanesulfonate (MMS), (±)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), 4-nitroquinoline-1-oxide (4NQO), styrene oxide and potassium bromate. MMS and potassium bromate were also tested by the modified comet assay with formamido pyrimidine glycosylase (FPG) protein. The results indicate that the mutagens tested induce DNA damage in PBMC and T cells in the same range of concentrations and removal of induced DNA lesions occurs to a comparable extent. Based on these results, we conclude that the comet assay with PBMC is suited to predict DNA damage and its removal in T cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased oxidative phosphorylation in response to acute and chronic DNA damage

PubMed Central

Brace, Lear E; Vose, Sarah C; Stanya, Kristopher; Gathungu, Rose M; Marur, Vasant R; Longchamp, Alban; Treviño-Villarreal, Humberto; Mejia, Pedro; Vargas, Dorathy; Inouye, Karen; Bronson, Roderick T; Lee, Chih-Hao; Neilan, Edward; Kristal, Bruce S; Mitchell, James R

2016-01-01

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa−/−|Xpa−/− mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes. PMID:28721274

Oxidative/nitrosative stress and antidepressants: targets for novel antidepressants.

PubMed

Lee, Seung-Yup; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

2013-10-01

The brain is an organ predisposed to oxidative/nitrosative stress. This is especially true in the case of aging as well as several neurodegenerative diseases. Under such circumstances, a decline in the normal antioxidant defense mechanisms leads to an increase in the vulnerability of the brain to the deleterious effects of oxidative damage. Highly reactive oxygen/nitrogen species damage lipids, proteins, and mitochondrial and neuronal genes. Unless antioxidant defenses react appropriately to damage inflicted by radicals, neurons may experience microalteration, microdysfunction, and degeneration. We reviewed how oxidative and nitrosative stresses contribute to the pathogenesis of depressive disorders and reviewed the clinical implications of various antioxidants as future targets for antidepressant treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects.

PubMed

Bhattacharya, Rahul; Singh, Poonam; John, Jebin Jacob; Gujar, Niranjan L

2018-04-03

Cyanide-induced chemical hypoxia is responsible for pronounced oxidative damage in the central nervous system. The disruption of mitochondrial oxidative metabolism has been associated with upregulation of uncoupling proteins (UCPs). The present study addresses the dose- and time-dependent effect of sub-acute cyanide exposure on various non-enzymatic and enzymatic oxidative stress markers and their correlation with inducible-nitric oxide synthase (iNOS) and uncoupling protein-2 (UCP-2) expression. Animals received (oral) triple distilled water (vehicle control), 0.25 LD50 potassium cyanide (KCN) or 0.50 LD50 KCN daily for 21 d. Animals were sacrificed on 7, 14 and 21 d post-exposure to measure serum cyanide and nitrite, and brain malondialdehyde (MDA), reduced glutathione (GSH), glutathione disulfide (GSSG), cytochrome c oxidase (CCO), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CA) levels, together with iNOS and UCP-2 expression, and DNA damage. The study revealed that a dose- and time-dependent increase in cyanide concentration was accompanied by corresponding CCO inhibition and elevated MDA levels. Decrease in GSH levels was not followed by reciprocal change in GSSG levels. Diminution of SOD, GPx, GR and CA activity was congruent with elevated nitrite levels and upregulation of iNOS and UCP-2 expression, without any DNA damage. It was concluded that long-term cyanide exposure caused oxidative stress, accompanied by upregulation of iNOS. The upregulation of UCP-2 further sensitized the cells to cyanide and accentuated the oxidative stress, which was independent of DNA damage.

Oxidative stress as a damage mechanism in porcine cumulus-oocyte complexes exposed to malathion during in vitro maturation.

PubMed

Flores, Diana; Souza, Verónica; Betancourt, Miguel; Teteltitla, Mario; González-Márquez, Humberto; Casas, Eduardo; Bonilla, Edmundo; Ramírez-Noguera, Patricia; Gutiérrez-Ruíz, María Concepción; Ducolomb, Yvonne

2017-06-01

Malathion is one of the most commonly used insecticides. Recent findings have demonstrated that it induces oxidative stress in somatic cells, but there are not enough studies that have demonstrated this effect in germ cells. Malathion impairs porcine oocyte viability and maturation, but studies have not shown how oxidative stress damages maturation and which biochemical mechanisms are affected in this process in cumulus-oocyte complexes (COCs). The aims of the present study were to determine the amount of oxidative stress produced by malathion in porcine COCs matured in vitro, to define how biochemical mechanisms affect this process, and determine whether trolox can attenuate oxidative damage. Sublethal concentrations 0, 750, and 1000 µM were used to evaluate antioxidant enzyme expressions, reactive oxygen species (ROS production), protein oxidation, and lipid peroxidation, among other oxidation products. COCs viability and oocyte maturation decreased in a concentration-dependent manner. Malathion increased Cu, Zn superoxide dismutase (SOD1), glutathione-S-transferase (GST), and glucose 6 phosphate dehydrogenase (G6PD) protein level and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) protein level. Species reactives of oxygen (ROS), protein oxidation and Thiobarbituric acid reactive substances (TBARS) levels increased in COCs exposed to the insecticide, but when COCs were pre-treated with the trolox (50 µM) 30 min before and during malathion exposure, these parameters decreased down to control levels. This study showed that malathion has a detrimental effect on COCs during in vitro maturation, inducing oxidative stress, while trolox attenuated malathion toxicity by decreasing oxidative damage. © 2017 Wiley Periodicals, Inc.

Classification of oxidative stress based on its intensity

PubMed Central

Lushchak, Volodymyr I.

2014-01-01

In living organisms production of reactive oxygen species (ROS) is counterbalanced by their elimination and/or prevention of formation which in concert can typically maintain a steady-state (stationary) ROS level. However, this balance may be disturbed and lead to elevated ROS levels called oxidative stress. To our best knowledge, there is no broadly acceptable system of classification of oxidative stress based on its intensity due to which proposed here system may be helpful for interpretation of experimental data. Oxidative stress field is the hot topic in biology and, to date, many details related to ROS-induced damage to cellular components, ROS-based signaling, cellular responses and adaptation have been disclosed. However, it is common situation when researchers experience substantial difficulties in the correct interpretation of oxidative stress development especially when there is a need to characterize its intensity. Careful selection of specific biomarkers (ROS-modified targets) and some system may be helpful here. A classification of oxidative stress based on its intensity is proposed here. According to this classification there are four zones of function in the relationship between “Dose/concentration of inducer” and the measured “Endpoint”: I – basal oxidative stress (BOS); II – low intensity oxidative stress (LOS); III – intermediate intensity oxidative stress (IOS); IV – high intensity oxidative stress (HOS). The proposed classification will be helpful to describe experimental data where oxidative stress is induced and systematize it based on its intensity, but further studies will be in need to clear discriminate between stress of different intensity. PMID:26417312

Study of the Genes and Mechanism Involved in the Radioadaptive Response

NASA Technical Reports Server (NTRS)

Dasgupta, Pushan R.

2009-01-01

The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor secreted by the cells that inhibits radioadaptation leading to the upregulation of some genes which initiates the response.

Polymeric micellar nanoplatforms for Fenton reaction as a new class of antibacterial agents.

PubMed

Park, Seong-Cheol; Kim, Nam-Hong; Yang, Wonseok; Nah, Jae-Woon; Jang, Mi-Kyeong; Lee, Dongwon

2016-01-10

Reactive oxygen species (ROS) produced by host phagocytes exert antibacterial action against a variety of pathogens and ROS-induced oxidative stress is the governing mechanism for the antibacterial activity of major bactericidal antibiotics. In particular, hydroxyl radical is a strong and nonselective oxidant which can damage biomolecules such as DNA, proteins and lipids. Ferrous ion is known to convert mild oxidant hydrogen peroxide (H2O2) into highly reactive and toxic hydroxyl radicals, referred to as Fenton reaction. Herein, we report a new class of antibacterial agents based on Fenton reaction-performing nanostructures, composed of H2O2-generating polymer (PCAE) and iron-containing ferrocene. Amphiphilic PCAE was designed to incorporate H2O2-generating cinnamaldehyde through acid-cleavable linkages and self-assemble to form thermodynamically stable micelles which could encapsulate ferrocene in their hydrophobic core. All the experiments in vitro display that ferrocene-loaded PCAE micelles produce hydroxyl radicals to kill Escherichia coli and Pseudomonas aeruginosa through membrane damages. Intraperitoneally injected ferrocene-loaded PCAE micelles significantly reduced the lung damages and therefore increased the survival rate of mice infected with drug resistant P. aeruginosa. Given their potent antibacterial activity, ferrocene-loaded PCAE micelles hold great potential as a new class of ROS-manipulating antibacterial agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells.

PubMed

Chang, Hsueh-Wei; Li, Ruei-Nian; Wang, Hui-Ru; Liu, Jing-Ru; Tang, Jen-Yang; Huang, Hurng-Wern; Chan, Yu-Hsuan; Yen, Ching-Yu

2017-01-01

Withaferin A (WFA) is one of the most active steroidal lactones with reactive oxygen species (ROS) modulating effects against several types of cancer. ROS regulation involves selective killing. However, the anticancer and selective killing effects of WFA against oral cancer cells remain unclear. We evaluated whether the killing ability of WFA is selective, and we explored its mechanism against oral cancer cells. An MTS tetrazolium cell proliferation assay confirmed that WFA selectively killed two oral cancer cells (Ca9-22 and CAL 27) rather than normal oral cells (HGF-1). WFA also induced apoptosis of Ca9-22 cells, which was measured by flow cytometry for subG1 percentage, annexin V expression, and pan-caspase activity, as well as western blotting for caspases 1, 8, and 9 activations. Flow cytometry analysis shows that WFA-treated Ca9-22 oral cancer cells induced G2/M cell cycle arrest, ROS production, mitochondrial membrane depolarization, and phosphorylated histone H2A.X (γH2AX)-based DNA damage. Moreover, pretreating Ca9-22 cells with N -acetylcysteine (NAC) rescued WFA-induced selective killing, apoptosis, G2/M arrest, oxidative stress, and DNA damage. We conclude that WFA induced oxidative stress-mediated selective killing of oral cancer cells.

Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells

PubMed Central

Chang, Hsueh-Wei; Li, Ruei-Nian; Wang, Hui-Ru; Liu, Jing-Ru; Tang, Jen-Yang; Huang, Hurng-Wern; Chan, Yu-Hsuan; Yen, Ching-Yu

2017-01-01

Withaferin A (WFA) is one of the most active steroidal lactones with reactive oxygen species (ROS) modulating effects against several types of cancer. ROS regulation involves selective killing. However, the anticancer and selective killing effects of WFA against oral cancer cells remain unclear. We evaluated whether the killing ability of WFA is selective, and we explored its mechanism against oral cancer cells. An MTS tetrazolium cell proliferation assay confirmed that WFA selectively killed two oral cancer cells (Ca9-22 and CAL 27) rather than normal oral cells (HGF-1). WFA also induced apoptosis of Ca9-22 cells, which was measured by flow cytometry for subG1 percentage, annexin V expression, and pan-caspase activity, as well as western blotting for caspases 1, 8, and 9 activations. Flow cytometry analysis shows that WFA-treated Ca9-22 oral cancer cells induced G2/M cell cycle arrest, ROS production, mitochondrial membrane depolarization, and phosphorylated histone H2A.X (γH2AX)-based DNA damage. Moreover, pretreating Ca9-22 cells with N-acetylcysteine (NAC) rescued WFA-induced selective killing, apoptosis, G2/M arrest, oxidative stress, and DNA damage. We conclude that WFA induced oxidative stress-mediated selective killing of oral cancer cells. PMID:28936177

Protective effect of Mangifera indica L. extract (Vimang) on the injury associated with hepatic ischaemia reperfusion.

PubMed

Sánchez, Gregorio Martínez; Rodríguez H, María A; Giuliani, Attilia; Núñez Sellés, Alberto J; Rodríguez, Niurka Pons; León Fernández, Olga Sonia; Re, L

2003-03-01

The effect of Mangifera indica L. extract (Vimang) on treatment of injury associated with hepatic ischaemia/reperfusion was tested. Vimang protects from the oxidative damage induced by oxygen-based free radicals as shown in several in vitro test systems conducted. The ability of Vimang to reduce liver damage was investigated in rats undergoing right-lobe blood fl ow occlusion for 45 min followed by 45 min of reperfusion. The ischaemia/reperfusion model leads to an increase of transaminase (ALT and AST), membrane lipid peroxidation, tissue neutrophil in filtration, DNA fragmentation, loss of protein -SH groups, cytosolic Ca2+ overload and a decrease of catalase activity. Oral administration of Vimang (50, 110 and 250 mg/kg, b.w.) 7 days before reperfusion, reduced transaminase levels and DNA fragmentation in a dose dependent manner (p < 0.05). Vimang also restored the cytosolic Ca2+ levels and inhibited polymorphonuclear migration at a dose of 250 mg/kg b.w., improved the oxidation of total and non protein sulfhydryl groups and prevented modification in catalase activity, uric acid and lipid peroxidation markers (p < 0.05). These data suggest that Vimang could be a useful new natural drug for preventing oxidative damage during hepatic injury associated with free radical generation. Copyright 2003 John Wiley & Sons, Ltd.

An electrochemical sensor based on polyaniline for monitoring hydroquinone and its damage on DNA.

PubMed

Tang, Wenwei; Zhang, Min; Li, Weihao; Zeng, Xinping

2014-09-01

A dsDNA/PANI/CTS/GCE biosensor was constructed by using the biocompatible chitosan (CTS) and the polyaniline (PANI) with excellent electric catalytic properties and large specific surface areas. The electrochemical behavior of hydroquinone on biosensor and its DNA-damaging mechanisms were investigated. Results showed that the redox peak current was remarkably increased after glassy carbon electrode (GCE) was modified by PANI/CTS. The dsDNA damage by hydroquinone was concentration dependent, and increased along with the increase of hydroquinone oxidation peak current and the reduction of dsDNA guanine oxidation peak current. The linear detection range of hydroquinone with dsDNA/PANI/CTS/GCE was 1.25×10(-6)-3.2×10(-4) M, and the detection limit was 9.65×10(-7) M. It was confirmed by the UV method that applying dsDNA/PANI/CTS/GCE to monitor hydroquinone was accurate and reliable. In addition, it could be deduced that the mode of interaction between the hydroquinone and dsDNA was intercalation. The electrochemical oxidation of hydroquinone on the dsDNA/PANI/CTS/GCE electrode was an adsorption-controlled irreversible and a two-electron two-proton transfer process. Copyright © 2014 Elsevier B.V. All rights reserved.

Age-dependent changes in nitric oxide synthase activity and protein expression in striata of mice transgenic for the Huntington's disease mutation.

PubMed

Pérez-Severiano, Francisca; Escalante, Bruno; Vergara, Paula; Ríos, Camilo; Segovia, José

2002-09-27

Huntington's disease (HD) is an autosomal hereditary neurodegenerative disorder caused by an abnormal expansion of the CAG repeats that code for a polyglutamine tract in a novel protein called huntingtin (htt). Both patients and experimental animals exhibit oxidative damage in specific areas of the brain, particularly the striatum. Nitric oxide (NO) is involved in many different physiological processes, and under pathological conditions it may promote oxidative damage through the formation of the highly reactive metabolite peroxynitrite; however, it may also play a role protecting cells from oxidative damage. We previously showed a correlation between the progression of the neurological phenotype and striatal oxidative damage in a line of transgenic mice, R6/1, which expresses a human mutated htt exon 1 with 116 CAG repeats. The purpose of the present work was to explore the participation of NO in the progressive oxidative damage that occurs in the striata of R6/1 mice. We analyzed the role of NO by measuring the activity of nitric oxide synthase (NOS) in the striata of transgenic and control mice at different ages. There was no difference in NOS activity between transgenic and wild-type mice at 11 weeks of age. In contrast, 19-week-old transgenic mice showed a significant increase in NOS activity, compared with same age controls. By 35 weeks of age, there was a decrease in NOS activity in transgenic mice when compared with wild-type controls. NOS protein expression was also determined in 11-, 19- and 35-week-old transgenic mice and wild-type littermates. Our results show increased neuronal NOS expression in 19-week-old transgenic mice, followed by a decreased level in 35-week-old mice, compared with controls, a phenomenon that parallels the changes in NOS enzyme activity. The present results suggest that NO is involved in the process leading to striatal oxidative damage and that it is associated with the onset of the progressive neurological phenotype in mice transgenic for the HD mutation.

Thermodynamic Signature of DNA Damage: Characterization of DNA with a 5-Hydroxy-2'-deoxycytidine•2'-Deoxyguanosine Base Pair

PubMed Central

Ganguly, Manjori; Szulik, Marta W.; Donahue, Patrick S.; Clancy, Kate; Stone, Michael P.; Gold, Barry

2012-01-01

Oxidation of DNA due to exposure to reactive oxygen species is a major source of DNA damage. One of the oxidation lesions formed, 5-hydroxy-2'-deoxycytidine, has been shown to miscode by some replicative DNA polymerases but not by error prone polymerases capable of translesion synthesis. The 5-hydroxy-2'-deoxycytidine lesion is repaired by DNA glycosylases that require the 5-hydroxycytidine base to be extrahelical so it can enter into the enzyme's active site where it is excised off the DNA backbone to afford an abasic site. The thermodynamic and NMR results presented herein, describe the effect of a 5-hydroxy-2'-deoxycytidine•2'-deoxyguanosine base pair on the stability of two different DNA duplexes. The results demonstrate that the lesion is highly destabilizing and that the energy barrier for the unstacking of 5-hydroxy-2'-deoxycytidine from the DNA duplex may be low. This could provide a thermodynamic mode of adduct identification by DNA glycosylases that require the lesion to be extrahelical. PMID:22332945

Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic exercise.

PubMed

Funes, Lorena; Carrera-Quintanar, Lucrecia; Cerdán-Calero, Manuela; Ferrer, Miguel D; Drobnic, Franchek; Pons, Antoni; Roche, Enrique; Micol, Vicente

2011-04-01

Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.

Frequency of polymorphism -262 c/t in catalase gene and oxidative damage in Slovak children with bronchial asthma.

PubMed

Babusikova, Eva; Jesenak, Milos; Evinova, Andrea; Banovcin, Peter; Dobrota, Dusan

2013-12-01

Bronchial asthma is a complex disease in which genetic factors, environmental factors and oxidative damage are responsible for the initiation and modulation of disease progression. If antioxidant mechanisms fail, reactive oxygen species damage the biomolecules followed by progression of the disease. Catalase is one of the most important endogenous enzymatic antioxidants. In the present study, we examined the hypothesis that increased oxidative damage and polymorphism in the CAT gene (-262 promoter region, C/T) are associated with childhood bronchial asthma. Genotyping of the polymorphisms in the CAT gene in healthy (249) and asthmatic children (248) was performed using polymerase chain reaction-restriction fragment length polymorphism. Markers of oxidative damage: content of sulfhydryl groups and thiobarbituric acid-reactive substances were determined by spectrophotometry in children. The TT genotype of catalase was more frequent among the asthmatic patients (22.6%) than in healthy children (4.8%) (odds ratio=5.63; 95% confidence interval=2.93-10.81, P<.001). The amount of sulfhydryl groups decreased significantly and conversely, the content of thiobarbituric acid-reactive substances increased significantly in bronchial asthma and in catalase TT genotype compared to other catalase genotypes of this gene. These results suggest that catalase polymorphism might participate in development of bronchial asthma and in enhanced oxidative damage in asthmatic children. Genetic variation of enzymatic antioxidants may modulate disease risk. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production.

PubMed

El-Amine, Rawan; Germini, Diego; Zakharova, Vlada V; Tsfasman, Tatyana; Sheval, Eugene V; Louzada, Ruy A N; Dupuy, Corinne; Bilhou-Nabera, Chrystèle; Hamade, Aline; Najjar, Fadia; Oksenhendler, Eric; Lipinski, Marс; Chernyak, Boris V; Vassetzky, Yegor S

2018-05-01

Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the contribution of HIV-1 to B-cell oncogenesis remains enigmatic. HIV-1 induces oxidative stress and DNA damage in infected cells via multiple mechanisms, including viral Tat protein. We have detected elevated levels of reactive oxygen species (ROS) and DNA damage in B-cells of HIV-infected individuals. As Tat is present in blood of infected individuals and is able to transduce cells, we hypothesized that it could induce oxidative DNA damage in B-cells promoting genetic instability and malignant transformation. Indeed, incubation of B-cells isolated from healthy donors with purified Tat protein led to oxidative stress, a decrease in the glutathione (GSH) levels, DNA damage and appearance of chromosomal aberrations. The effects of Tat relied on its transcriptional activity and were mediated by NF-κB activation. Tat stimulated oxidative stress in B-cells mostly via mitochondrial ROS production which depended on the reverse electron flow in Complex I of respiratory chain. We propose that Tat-induced oxidative stress, DNA damage and chromosomal aberrations are novel oncogenic factors favoring B-cell lymphomas in HIV-1 infected individuals. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Secoisolariciresinol Diglucoside Abrogates Oxidative Stress-Induced Damage in Cardiac Iron Overload Condition

PubMed Central

Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

2015-01-01

Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload. PMID:25822525

Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

PubMed

Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

2015-01-01

Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

Protective effect of Uncaria tomentosa extract against oxidative stress and genotoxicity induced by glyphosate-Roundup® using zebrafish (Danio rerio) as a model.

PubMed

Santo, Glaucia Dal; Grotto, Alan; Boligon, Aline A; Da Costa, Bárbara; Rambo, Cassiano L; Fantini, Emily A; Sauer, Elisa; Lazzarotto, Luan M V; Bertoncello, Kanandra T; Júnior, Osmar Tomazelli; Garcia, Solange C; Siebel, Anna M; Rosemberg, Denis B; Magro, Jacir Dal; Conterato, Greicy M M; Zanatta, Leila

2018-04-01

Oxidative stress and DNA damage are involved in the glyphosate-based herbicide toxicity. Uncaria tomentosa (UT; Rubiaceae) is a plant species from South America containing bioactive compounds with known beneficial properties. The objective of this work was to evaluate the antioxidant and antigenotoxic potential of UT extract in a model of acute exposure to glyphosate-Roundup® (GR) in zebrafish (Danio rerio). We showed that UT (1.0 mg/mL) prevented the decrease of brain total thiols, the increase of lipid peroxidation in both brain and liver, and the decrease of liver GPx activity caused after 96 h of GR (5.0 mg/L) exposure. In addition, UT partially protected against the increase of micronucleus frequency induced by GR exposure in fish brain. Overall, our results indicate that UT protects against damage induced by a glyphosate-based herbicide by providing antioxidant and antigenotoxic effects, which may be related to the phenolic compounds identified in the extract.

DNA glycosylases search for and remove oxidized DNA bases.

PubMed

Wallace, Susan S

2013-12-01

This review article presents, an overview of the DNA glycosylases that recognize oxidized DNA bases using the Fpg/Nei family of DNA glycosylases as models for how structure can inform function. For example, even though human NEIL1 and the plant and fungal orthologs lack the zinc finger shown to be required for binding, DNA crystal structures revealed a "zincless finger" with the same properties. Moreover, the "lesion recognition loop" is not involved in lesion recognition, rather, it stabilizes 8-oxoG in the active site pocket. Unlike the other Fpg/Nei family members, Neil3 lacks two of the three void-filling residues that stabilize the DNA duplex and interact with the opposite strand to the damage which may account for its preference for lesions in single-stranded DNA. Also single-molecule approaches show that DNA glycosylases search for their substrates in a sea of undamaged DNA by using a wedge residue that is inserted into the DNA helix to probe for the presence of damage. Copyright © 2013 Wiley Periodicals, Inc.

Effect of Environmental Exposures on Fatigue Life of P/M Disk Superalloys

NASA Technical Reports Server (NTRS)

Draper, Susan

2011-01-01

As the temperature capability of Ni-base superalloy powder metallurgy disks is steadily increased, environmental resistance and protection of advanced nickel-based turbine disk components are becoming increasingly important. Localized surface hot corrosion attack and damage from oxidation have been shown to impair disk fatigue life and may eventually limit disk operating temperatures. NASA Research Announcement (NRA) contracts have been awarded to GE Aviation and Honeywell Aerospace to separately develop fatigue resistant metallic and ceramic coatings for corrosion resistance and the corrosion/fatigue results of selected coatings will be presented. The microstructural response of a bare ME3 disk superalloy has been evaluated for moderate (704 C) and aggressive (760-816 C) oxidizing exposures up to 2,020 hours. Cross section analysis reveals sub-surface damage (significant for aggressive exposures) that consists of Al2O3 "fingers", interfacial voids, a recrystallized precipitate-free layer and GB carbide dissolution. The effects of a Nichrome corrosion coating on this microstructural response will also be presented.

High affinity hemoglobin and Parkinson's disease.

PubMed

Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

2014-12-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential responses of juvenile and adult South African abalone (Haliotis midae Linnaeus) to low and high oxygen levels.

PubMed

Vosloo, Andre; Laas, Anél; Vosloo, Dalene

2013-01-01

Marine invertebrates have evolved multiple responses to naturally variable environmental oxygen, all aimed at either maintaining cellular oxygen homeostasis or limiting cellular damage during or after hypoxic or hyperoxic events. We assessed organismal (rates of oxygen consumption and ammonia excretion) and cellular (heat shock protein expression, anti-oxidant enzymes) responses of juvenile and adult abalone exposed to low (~83% of saturation), intermediate (~95% of saturation) and high (~115% of saturation) oxygen levels for one month. Using the Comet assay, we measured DNA damage to determine whether the observed trends in the protective responses were sufficient to prevent oxidative damage to cells. Juveniles were unaffected by moderately hypoxic and hyperoxic conditions. Elevated basal rates of superoxide dismutase, glutathione peroxidase and catalase were sufficient to prevent DNA fragmentation and protein damage. Adults, with their lower basal rate of anti-oxidant enzymes, had increased DNA damage under hypoxic and hyperoxic conditions, indicating that the antioxidant enzymes were unable to prevent oxidative damage under hypoxic and hyperoxic conditions. The apparent insensitivity of juvenile abalone to decreased and increased oxygen might be related to their life history and development in algal and diatom biofilms where they are exposed to extreme diurnal fluctuations in dissolved oxygen levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.

PubMed

Lopez-Gonzalez, Rodrigo; Lu, Yubing; Gendron, Tania F; Karydas, Anna; Tran, Helene; Yang, Dejun; Petrucelli, Leonard; Miller, Bruce L; Almeida, Sandra; Gao, Fen-Biao

2016-10-19

GGGGCC repeat expansions in C9ORF72 are the most common genetic cause of both ALS and FTD. To uncover underlying pathogenic mechanisms, we found that DNA damage was greater, in an age-dependent manner, in motor neurons differentiated from iPSCs of multiple C9ORF72 patients than control neurons. Ectopic expression of the dipeptide repeat (DPR) protein (GR) 80 in iPSC-derived control neurons increased DNA damage, suggesting poly(GR) contributes to DNA damage in aged C9ORF72 neurons. Oxidative stress was also increased in C9ORF72 neurons in an age-dependent manner. Pharmacological or genetic reduction of oxidative stress partially rescued DNA damage in C9ORF72 neurons and control neurons expressing (GR) 80 or (GR) 80 -induced cellular toxicity in flies. Moreover, interactome analysis revealed that (GR) 80 preferentially bound to mitochondrial ribosomal proteins and caused mitochondrial dysfunction. Thus, poly(GR) in C9ORF72 neurons compromises mitochondrial function and causes DNA damage in part by increasing oxidative stress, revealing another pathogenic mechanism in C9ORF72-related ALS and FTD. Copyright © 2016 Elsevier Inc. All rights reserved.

Temperature of frozen storage affects the nature and consequences of protein oxidation in beef patties.

PubMed

Utrera, Mariana; Morcuende, David; Estévez, Mario

2014-03-01

The effect of three frozen storage temperatures (-8, -18 and -80 °C) on protein oxidation in beef patties was studied through the analysis of novel oxidation markers. Additionally, the connection between lipid and protein oxidation and the impact of the latter on particular quality traits (water holding capacity, color and texture) of subsequently processed beef patties (cooking/cold-stored) were investigated. Protein oxidation was measured as the loss of tryptophan fluorescence and formation of diverse lysine oxidation products (α-aminoadipic semialdehyde, α-aminoadipic acid and Schiff bases). Lipid oxidation was assessed by levels of thiobarbituric acid reactive substances and hexanal. A significant effect of storage temperature on protein oxidation was detected. Frozen storage increased the susceptibility of meat proteins to undergo further oxidation during processing. Timely interactions were found between lipid and protein oxidation. Plausible mechanisms by which oxidative damage to proteins may have an impact in particular quality traits are thoroughly discussed. © 2013.

A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers.

PubMed

Del Bó, Cristian; Riso, Patrizia; Campolo, Jonica; Møller, Peter; Loft, Steffen; Klimis-Zacas, Dorothy; Brambilla, Ada; Rizzolo, Anna; Porrini, Marisa

2013-03-01

It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans. The aim of the study was to investigate the effect of one portion (300 g) of blueberries on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in male subjects. In a randomized cross-over design, separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly. Before and after consumption (at 1, 2, and 24 hours), blood samples were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed by means of Endo-PAT 2000. Blueberries significantly reduced (P < .01) H(2)O(2)-induced DNA damage (-18%) 1 hour after blueberry consumption compared to control. No significant differences were observed for endogenous DNA damage, peripheral arterial function and nitric oxide levels after blueberry intake. In conclusion, one portion of blueberries seems sufficient to improve cell antioxidant defense against DNA damage, but further studies are necessary to understand their role on vascular function. Copyright © 2013 Elsevier Inc. All rights reserved.

SIRT3 mediates decrease of oxidative damage and prevention of ageing in porcine fetal fibroblasts.

PubMed

Xie, Xiaoxian; Wang, Liangliang; Zhao, Binggong; Chen, Yangyang; Li, Jiaqi

2017-05-15

Sirtuin 3 (SIRT3) is a mitochondria-specific protein required for the deacetylation of metabolic enzymes and the action of oxidative phosphorylation by acting as a nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase. SIRT3 increases oxidative stress resistance and prevents mitochondrial decay associated with ageing in response to caloric restriction. However, the effects of SIRT3 on oxidative damage and ageing are not well understood. We investigated the physiological functions of porcine SIRT3 on the damage and ageing in porcine fetal fibroblasts (PFFs). Overexpression and knockdown of SIRT3 were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. All cells were treated with three different stress reagents 12-o-tetradecanoylphorbol-13-acetate (TPA), methanesulfonic acid methylester (MMS), and tert-butylhydroperoxide (t-BHP), respectively, and then examined by flow cytometry following JC-1 (5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazol-carbocyanine iodide) staining. SIRT3 overexpression enhanced the ability of superoxide dismutase 2 (SOD2) to reduce cellular reactive oxygen species (ROS), which further decreased the damage to the membranes and the organelles of the cells, especially to mitochondria. It inhibited the initial decrease of mitochondrial membrane potential, and prevented the decrease of adenosine triphosphate (ATP) production and activity of Nampt. In contrast, SIRT3 knockdown reduced the ability of SOD2 to increase cellular ROS which was directly correlated with stress-induced oxidative damage and ageing in PFFs. Our findings identify one function of SIRT3 in PFFs was to dampen cytotoxicity, and, therefore, to decrease oxidative damage and attenuate ageing possibly by enhancing the activity of SOD2. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxidative Burst of Circulating Neutrophils Following Traumatic Brain Injury in Human

PubMed Central

Liao, Yiliu; Liu, Peng; Guo, Fangyuan; Zhang, Zhi-Yuan; Zhang, Zhiren

2013-01-01

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. PMID:23894384

Analysis of liver damage from radon, X-ray, or alcohol treatments in mice using a self-organizing map.

PubMed

Kanzaki, Norie; Kataoka, Takahiro; Etani, Reo; Sasaoka, Kaori; Kanagawa, Akihiro; Yamaoka, Kiyonori

2017-01-01

In our previous studies, we found that low-dose radiation inhibits oxidative stress-induced diseases due to increased antioxidants. Although these effects of low-dose radiation were demonstrated, further research was needed to clarify the effects. However, the analysis of oxidative stress is challenging, especially that of low levels of oxidative stress, because antioxidative substances are intricately involved. Thus, we proposed an approach for analysing oxidative liver damage via use of a self-organizing map (SOM)-a novel and comprehensive technique for evaluating hepatic and antioxidative function. Mice were treated with radon inhalation, irradiated with X-rays, or subjected to intraperitoneal injection of alcohol. We evaluated the oxidative damage levels in the liver from the SOM results for hepatic function and antioxidative substances. The results showed that the effects of low-dose irradiation (radon inhalation at a concentration of up to 2000 Bq/m 3 , or X-irradiation at a dose of up to 2.0 Gy) were comparable with the effect of alcohol administration at 0.5 g/kg bodyweight. Analysis using the SOM to discriminate small changes was made possible by its ability to 'learn' to adapt to unexpected changes. Moreover, when using a spherical SOM, the method comprehensively examined liver damage by radon, X-ray, and alcohol. We found that the types of liver damage caused by radon, X-rays, and alcohol have different characteristics. Therefore, our approaches would be useful as a method for evaluating oxidative liver damage caused by radon, X-rays and alcohol. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway.

PubMed

Cui, Qunli; Li, Xin; Zhu, Hongcan

2016-02-01

Parkinson's disease (PD) is an age-related complex neurodegenerative disease that affects ≤ 80% of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It has previously been suggested that mitochondrial dysfunction, oxidative stress and oxidative damage underlie the pathogenesis of PD. Curcumin, which is a major active polyphenol component extracted from the rhizomes of Curcuma longa (Zingiberaceae), has been reported to exert neuroprotective effects on an experimental model of PD. The present study conducted a series of in vivo experiments, in order to investigate the effects of curcumin on behavioral deficits, oxidative damage and related mechanisms. The results demonstrated that curcumin was able to significantly alleviate motor dysfunction and increase suppressed tyrosine hydroxylase (TH) activity in the SNpc of rotenone (ROT)-injured rats. Biochemical measurements indicated that rats pretreated with curcumin exhibited increased glutathione (GSH) levels, and reduced reactive oxygen species activity and malondialdehyde content. Mechanistic studies demonstrated that curcumin significantly restored the expression levels of heme oxygenase-1 and quinone oxidoreductase 1, thus ameliorating ROT-induced damage in vivo, via the phosphorylation of Akt and nuclear factor erythroid 2-related factor 2 (Nrf2). Further studies indicated that the Akt/Nrf2 signaling pathway was associated with the protective role of curcumin in ROT-treated rats. Inhibiting the Akt/Nrf2 pathway using a lentiviral vector containing Nrf2-specific short hairpin RNA, or the phosphoinositide 3-kinase inhibitor LY294002, markedly reduced the expression levels of TH and GSH, ultimately attenuating the neuroprotective effects of curcumin against oxidative damage. These results indicated that curcumin was able to significantly ameliorate ROT-induced dopaminergic neuronal oxidative damage in the SNpc of rats via activation of the Akt/Nrf2 signaling pathway.

Protective effect of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats.

PubMed

Kumar, Anil; Dogra, Samrita; Prakash, Atish

2009-12-28

Aluminium is a potent neurotoxin and has been associated with Alzheimer's disease (AD) causality for decades. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. Current treatment modalities for AD provide only symptomatic relief thus necessitating the development of new drugs with fewer side effects. The aim of the study was to demonstrate the protective effect of chronic curcumin administration against aluminium-induced cognitive dysfunction and oxidative damage in rats. Aluminium chloride (100 mg/kg, p.o.) was administered to rats daily for 6 weeks. Rats were concomitantly treated with curcumin (per se; 30 and 60 mg/kg, p.o.) daily for a period of 6 weeks. On the 21st and 42nd day of the study behavioral studies to evaluate memory (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity and aluminium concentration in aluminium treated rats. Chronic administration of curcumin significantly improved memory retention in both tasks, attenuated oxidative damage, acetylcholinesterase activity and aluminium concentration in aluminium treated rats (P<0.05). Curcumin has neuroprotective effects against aluminium-induced cognitive dysfunction and oxidative damage.

Prophylaxis with Bacopa monnieri attenuates acrylamide induced neurotoxicity and oxidative damage via elevated antioxidant function.

PubMed

Shinomol, George Kunnel; Raghunath, Narayanareddy; Bharath, Muchukunte Mukunda Srinivas; Muralidhara

2013-03-01

Acrylamide (ACR) is a water-soluble, vinyl monomer that has multiple chemical and industrial applications. Exposure to ACR causes neuropathy and associated neurological defects including gait abnormalities and skeletal muscle weakness, due to impaired neurotransmitter release and eventual neurodegeneration. Using in vivo and in vitro models, we examined whether oxidative events are involved in ACR-mediated neurotoxicity and whether these could be prevented by natural plant extracts. Administration (i.p.) of ACR in mice (40 mg/kg bw/ d for 5d) induced significant oxidative damage in the brain cortex and liver as evidenced by elevated lipid peroxidation, reactive oxygen species and protein carbonyls. This was associated with lowered antioxidant activities including antioxidant enzymes (catalase, glutathione-s-transferase) and reduced glutathione (GSH) compared to untreated controls. Similarly, exposure of N27 neuronal cells in culture to ACR (1-5 mM) caused dose-dependent neuronal death and lowered GSH. Interestingly, dietary supplementation with the leaf powder of Bacopa monnieri (BM) (which possesses neuroprotective properties and nootropic activity) in mice for 30 days offered significant protection against ACR toxicity and oxidative damage in vivo. Similarly, pretreatment with BM protected the N27 cells against ACR-induced cell death and associated oxidative damage. Co-treatment and pre-treatment of Drosophila melanogaster with BM extract protected against ACR-induced locomotor dysfunction and GSH depletion. We infer that BM displays prophylactic effects against ACR induced oxidative damage and neurotoxicity with potential therapeutic application in human pathology associated with neuropathy.

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration.

PubMed

Pietrofesa, Ralph A; Turowski, Jason B; Arguiri, Evguenia; Milovanova, Tatyana N; Solomides, Charalambos C; Thom, Stephen R; Christofidou-Solomidou, Melpo

2013-09-30

Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O 2 (O 2 ); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O 2 and IR (O 2 +IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O 2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis ( p <0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group. We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration.

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration

PubMed Central

Pietrofesa, Ralph A; Turowski, Jason B; Arguiri, Evguenia; Milovanova, Tatyana N; Solomides, Charalambos C; Thom, Stephen R; Christofidou-Solomidou, Melpo

2013-01-01

Background Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Methods Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Results Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis (p<0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group. Conclusion We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration. PMID:24358450

Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases

PubMed Central

Li, Haifeng; Ding, Fei; Xiao, Lingyun; Shi, Ruona; Wang, Hongyu; Han, Wenjing

2017-01-01

Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities. PMID:28753972

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice.

PubMed

Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

2017-04-01

Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro-/anti-oxidative homeostasis.

Inactivation of thiol-dependent enzymes by hypothiocyanous acid: role of sulfenyl thiocyanate and sulfenic acid intermediates

PubMed Central

Barrett, Tessa J.; Pattison, David I.; Leonard, Stephen E.; Carroll, Kate S.; Davies, Michael J.; Hawkins, Clare L.

2012-01-01

Myeloperoxidase (MPO) forms reactive oxidants including hypochlorous and hypothiocyanous acids (HOCl and HOSCN) under inflammatory conditions. HOCl causes extensive tissue damage and plays a role in the progression of many inflammatory-based diseases. Although HOSCN is a major MPO oxidant, particularly in smokers, who have elevated plasma thiocyanate, the role of this oxidant in disease is poorly characterized. HOSCN induces cellular damage by targeting thiols. However, the specific targets and mechanisms involved in this process are not well defined. We show that exposure of macrophages to HOSCN results in the inactivation of intracellular enzymes, including creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In each case, the active-site thiol residue is particularly sensitive to oxidation, with evidence for reversible inactivation and the formation of sulfenyl thiocyanate and sulfenic acid intermediates, on treatment with HOSCN (less than fivefold molar excess). Experiments with DAz-2, a cell-permeable chemical trap for sulfenic acids, demonstrate that these intermediates are formed on many cellular proteins, including GAPDH and CK, in macrophages exposed to HOSCN. This is the first direct evidence for the formation of protein sulfenic acids in HOSCN-treated cells and highlights the potential of this oxidant to perturb redox signaling processes. PMID:22248862

Mitochondrial quality control: decommissioning power plants in neurodegenerative diseases.

PubMed

Mukherjee, Rukmini; Chakrabarti, Oishee

2013-01-01

The cell has an intricate quality control system to protect its mitochondria from oxidative stress. This surveillance system is multi-tiered and comprises molecules that are present inside the mitochondria, in the cytosol, and in other organelles like the nucleus and endoplasmic reticulum. These molecules cross talk with each other and protect the mitochondria from oxidative stress. Oxidative stress is a fundamental part of early disease pathogenesis of neurodegenerative diseases. These disorders also damage the cellular quality control machinery that protects the cell against oxidative stress. This exacerbates the oxidative damage and causes extensive neuronal cell death that is characteristic of neurodegeneration.

Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles

PubMed Central

Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Verma, Ankit; Ahamed, Maqusood; Ahmed, Mukhtar; Alhadlaq, Hisham A

2013-01-01

The widespread use of zinc oxide (ZnO) nanoparticles worldwide exposes humans to their adverse effects, so it is important to understand their biological effects and any associated risks. This study was designed to investigate the cytotoxicity, oxidative stress, and apoptosis caused by ZnO nanoparticles in human skin melanoma (A375) cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and lactate dehydrogenase-based cell viability assays showed a significant decrease in cell viability after exposure to ZnO nanoparticles, and phase contrast images revealed that cells treated with these nanoparticles had a lower density and a rounded morphology. ZnO nanoparticles were also found to induce oxidative stress, evidenced by generation of reactive oxygen species and depletion of the antioxidant, glutathione. Induction of apoptosis was confirmed by chromosomal condensation assay and caspase-3 activation. Further, more DNA damage was observed in cells exposed to the highest concentration of ZnO nanoparticles. These results demonstrate that ZnO nanoparticles have genotoxic potential in A375 cells, which may be mediated via oxidative stress. Our short-term exposure study showing induction of a genotoxic and apoptotic response to ZnO nanoparticles needs further investigation to determine whether there may be consequences of long-term exposure to ZnO nanoparticles. PMID:23493450

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

PubMed Central

Peterson, Tina M.L.; Luckhart, Shirley

2008-01-01

Malaria parasite infection in anopheline mosquitoes induces nitrosative and oxidative stresses that limit parasite development, but also damage mosquito tissues in proximity to the response. Based on these observations, we proposed that cellular defenses in the mosquito may be induced to minimize self-damage. Specifically, we hypothesized that peroxiredoxins (Prxs), enzymes known to detoxify reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), protect mosquito cells. We identified an Anopheles stephensi 2-Cys Prx ortholog of Drosophila melanogaster Prx-4783, which protects fly cells against oxidative stresses. To assess function, AsPrx-4783 was overexpressed in D. melanogaster (S2) and in A. stephensi (MSQ43) cells and silenced in MSQ43 cells with RNA interference before treatment with various ROS and RNOS. Our data revealed that AsPrx-4783 and DmPrx-4783 differ in host cell protection and that AsPrx-4783 protects A. stephensi cells against stresses that are relevant to malaria parasite infection in vivo, namely nitric oxide (NO), hydrogen peroxide, nitroxyl, and peroxynitrite. Further, AsPrx-4783 expression is induced in the mosquito midgut by parasite infection at times associated with peak nitrosative and oxidative stresses. Hence, whereas the NO-mediated defense response is toxic to both host and parasite, AsPrx-4783 may shift the balance in favor of the mosquito. PMID:16540402

Protective effect of acetyl-L-carnitine on propofol-induced toxicity in embryonic neural stem cells.

PubMed

Liu, Fang; Rainosek, Shuo W; Sadovova, Natalya; Fogle, Charles M; Patterson, Tucker A; Hanig, Joseph P; Paule, Merle G; Slikker, William; Wang, Cheng

2014-05-01

Propofol is a widely used general anesthetic. A growing body of data suggests that perinatal exposure to general anesthetics can result in long-term deleterious effects on brain function. In the developing brain there is evidence that general anesthetics can cause cell death, synaptic remodeling, and altered brain cell morphology. Acetyl-L-carnitine (L-Ca), an anti-oxidant dietary supplement, has been reported to prevent neuronal damage from a variety of causes. To evaluate the ability of L-Ca to protect against propofol-induced neuronal toxicity, neural stem cells were isolated from gestational day 14 rat fetuses and on the eighth day in culture were exposed for 24h to propofol at 10, 50, 100, 300 and 600 μM, with or without L-Ca (10 μM). Markers of cellular proliferation, mitochondrial health, cell death/damage and oxidative damage were monitored to determine: (1) the effects of propofol on neural stem cell proliferation; (2) the nature of propofol-induced neurotoxicity; (3) the degree of protection afforded by L-Ca; and (4) to provide information regarding possible mechanisms underlying protection. After propofol exposure at a clinically relevant concentration (50 μM), the number of dividing cells was significantly decreased, oxidative DNA damage was increased and a significant dose-dependent reduction in mitochondrial function/health was observed. No significant effect on lactase dehydrogenase (LDH) release was observed at propofol concentrations up to 100 μM. The oxidative damage at 50 μM propofol was blocked by L-Ca. Thus, clinically relevant concentrations of propofol induce dose-dependent adverse effects on rat embryonic neural stem cells by slowing or stopping cell division/proliferation and causing cellular damage. Elevated levels of 8-oxoguanine suggest enhanced oxidative damage [reactive oxygen species (ROS) generation] and L-Ca effectively blocks at least some of the toxicity of propofol, presumably by scavenging oxidative species and/or reducing their production. Published by Elsevier B.V.

AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE.

EPA Science Inventory

Ambient particulate matter (PM) damages biological targets through oxidative stress (OS) pathways. Several reports indicate that the brain is one of those targets. Since microglia (brain macrophage) are critical to OS-mediated neurodegeneration, their response to concentrated amb...

The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome

PubMed Central

Reeg, Sandra; Jung, Tobias; Castro, José P.; Davies, Kelvin J.A.; Henze, Andrea; Grune, Tilman

2016-01-01

One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. PMID:27498116

The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome.

PubMed

Reeg, Sandra; Jung, Tobias; Castro, José P; Davies, Kelvin J A; Henze, Andrea; Grune, Tilman

2016-10-01

One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: Potential role of the thiol antioxidant N-acetylcysteine amide

PubMed Central

Banerjee, Atrayee; Zhang, Xinsheng; Manda, Kalyan Reddy; Banks, William A; Ercal, Nuran

2010-01-01

An increased risk of HIV-1 associated dementia (HAD) has been observed in patients abusing methamphetamine (METH). Since both HIV viral proteins (gp120, Tat) and METH induce oxidative stress, drug abusing patients are at a greater risk of oxidative stress-induced damage. The objective of this study was to determine if N-acetylcysteine amide (NACA) protects the blood brain barrier (BBB) from oxidative stress-induced damage in animals exposed to gp120, Tat and METH. To study this, CD-1 mice pre-treated with NACA/saline, received injections of gp120, Tat, gp120 + Tat or saline for 5 days, followed by three injections of METH/saline on the fifth day, and sacrificed 24 h after the final injection. Various oxidative stress parameters were measured, and animals treated with gp120+Tat+Meth were found to be the most challenged group, as indicated by their GSH and MDA levels. Treatment with NACA significantly rescued the animals from oxidative stress. Further, NACA-treated animals had significantly higher expression of TJ proteins and BBB permeability as compared to the group treated with gp120+Tat+METH alone, indicating that NACA can protect the BBB from oxidative stress-induced damage in gp120, Tat and METH exposed animals, and thus could be a viable therapeutic option for patients with HAD. PMID:20188164

Genotoxic and oxidative effects induced on A549 cells by extract of PM10 collected in an electric steel plant.

PubMed

Cavallo, Delia; Ursini, Cinzia L; Maiello, Raffaele; Apostoli, Pietro; Catalani, Simona; Ciervo, Aureliano; Iavicoli, Sergio

2008-01-01

The present study was aimed at assessing the carcinogenic risk of occupational exposure to PM10 in electric steel plants. PM10 was collected on cellulose filter respectively outside (site 1) and inside (site 2) the furnace area, was measured, extracted and its metal content was analysed by ICP-MS. Cells were exposed for 30 min, 2 and 4 hours to extract of filter from each site diluted at 0.004, 0.008 and 0.02%. The direct/oxidative DNA damage caused by PM10 was evaluated on A549 cells by Fpg-modified comet assay, analysing Tail moment (TM) and comet percentage. Air samples contained 1.08 mg/m3 of PM10 in site 1 and 5.54 mg/m3in site 2 and different amounts of metals with higher levels of Zn, Al, Ni, Pb, Cd, Cr, Ba in site 2 and of Fe, Mn, Sb in site 1. In cells exposed for 2h to PM10 from both sites, an oxidative DNA damage was found concentrations of 0.008% and 0.02%. For site 2, a direct DNA damage at 0.02% was also found. After 4h a direct/oxidative DNA damage was detected at 0.02% for site 2 and an oxidative DNA damage for site 1. The results indicate a moderate DNA damage induction by used diluitions of PM10 extracts with higher extent for more polluted site 2. These findings show the suitability of this experimental model to evaluate early DNA damage induced by complex mixtures containing metals on target organ, suggesting its use to study biological effects of occupational exposure to such substances.

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

Elhadj, Selim; Yoo, Jae-hyuck; Negres, Raluca A.

The optical damage performance of electrically conductive gallium nitride (GaN) and indium tin oxide (ITO) films is addressed using large area, high power laser beam exposures at 1064 nm sub-bandgap wavelength. Analysis of the laser damage process assumes that onset of damage (threshold) is determined by the absorption and heating of a nanoscale region of a characteristic size reaching a critical temperature. We use this model to rationalize semi-quantitatively the pulse width scaling of the damage threshold from picosecond to nanosecond timescales, along with the pulse width dependence of the damage threshold probability derived by fitting large beam damage densitymore » data. Multi-shot exposures were used to address lifetime performance degradation described by an empirical expression based on the single exposure damage model. A damage threshold degradation of at least 50% was observed for both materials. Overall, the GaN films tested had 5-10 × higher optical damage thresholds than the ITO films tested for comparable transmission and electrical conductivity. This route to optically robust, large aperture transparent electrodes and power optoelectronics may thus involve use of next generation widegap semiconductors such as GaN.« less

Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced oxidative damage: a protocol for a systematic review.

PubMed

Dludla, Phiwayinkosi V; Nkambule, Bongani B; Dias, Stephanie C; Johnson, Rabia

2017-05-12

Hyperglycaemia-induced oxidative damage is a well-established factor implicated in the development of diabetic cardiomyopathy (DCM) in diabetic individuals. Some of the well-known characteristics of DCM include increased myocardial left ventricular wall thickness and remodelling that result in reduced cardiac efficiency. To prevent this, an increasing number of pharmacological compounds such as N-acetyl cysteine (NAC) are explored for their antioxidant properties. A few studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart. Hence, the objective of this review is to synthesise the available evidence pertaining to the cardioprotective role of NAC against hyperglycaemia-induced oxidative damage and thus prevent DCM. This systematic review protocol will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. We will perform a comprehensive search on major databases such as EMBASE, Cochrane Library, PubMed and Google scholar for original research articles published from January 1960 to March 2017. We will only report on literature that is available in English. Two authors will independently screen for eligible studies using pre-defined criteria, and data extraction will be done in duplicate. All discrepancies will be resolved by consensus or consultation of a third reviewer. The quality of studies will be checked using Cochrane Risk of Bias Assessment Tool and The Joanna Briggs Institute (JBI) Critical Appraisal tools for non-randomised experimental studies. Heterogeneity across studies will be assessed using the Cochrane Q statistic and the inconsistency index (I 2 ). We will use the random effects model to calculate a pooled estimate. Although several studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart, this systematic review will be the first pre-registered synthesis of data to identify the cardioprotective potential of NAC against hyperglycaemia-induced oxidative damage. This result will help guide future research evaluating the cardioprotective role of NAC against DCM and better identify possible mechanisms of action for NAC to prevent oxidative damage with a diabetic heart. PROSPERO CRD42017055851 .

Fe-Cr-Mo based ODS alloys via spark plasma sintering: A combinational characterization study by TEM and APT

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

Y. Q. Wu; K. N. Allahar; J. Burns

2013-08-01

Nanoscale oxides play an important role in oxide dispersion strengthened (ODS) alloys for improved high temperature creep resistance and enhanced radiation damage tolerance. In this study, transmission electron microscopy (TEM) and atom probe tomography (APT) were combined to investigate two novel Fe-16Cr-3Mo (wt.%) based ODS alloys. Spark plasma sintering (SPS) was used to consolidate the ODS alloys from powders that were milled with 0.5 wt.% Y2O3 powder only or with Y2O3 powder and 1 wt.% Ti. TEM characterization revealed that both alloys have a bimodal structure of nanometer-size (~ 100 – 500 nm) and micron-size grains with nanostructured oxide precipitatesmore » formed along and close to grain boundaries with diameters ranging from five to tens of nanometers. APT provides further quantitative analyses of the oxide precipitates, and also reveals Mo segregation at grain boundaries next to oxide precipitates. The alloys with and without Ti are compared based on their microstructures.« less

Effect of oxidative stress from nanoscale TiO2 particles on a Physarum polycephalum macroplasmodium under dark conditions.

PubMed

Zhang, Zhi; Zhang, Jianhua; Shi, Caixia; Guo, Heng; Ni, RuiYang; Qu, Junle; Tang, Jiaoning; Liu, Shide

2017-07-01

Information regarding the effect of nanoscale titanium dioxide particles (nTiO 2 ) on the environment under dark conditions is scarce, and the effect of nTiO 2 on fungi is largely unknown. Due to its huge size and high sensitivity to external stimuli, the slime mold fungi cell, Physarum polycephalum macroplasmodium, was utilized as a novel subject for the toxicity investigations in the present study, and oxidative stress from nTiO 2 on the macroplasmodium was assessed under dark conditions. Short exposure (2-3 h) caused an intracellular reactive oxygen species (ROS) imbalance, and an anti-oxidative mechanism was activated from intermediate doses of nTiO 2 (5-18 mg/mL). At long exposure times (~3 days), relatively low doses of nTiO 2 (≤9 mg/mL) stimulated the growth of macroplasmodium and oxidative stress without DNA damage, whereas higher doses of nTiO 2 (≥15 mg/mL) led to growth inhibition, significant DNA oxidative damage, and activation of the DNA single-strand repairing system. Although DNA oxidative damage was decreased to the same level as the control group by the supplementation of the anti-oxidant vitamin C, growth of the macroplasmodium failed to be completely restored. We inferred that nTiO 2 induced a complicated toxicity effect on P. polycephalum in addition to DNA oxidative damage. Taken as a whole, the present study implied the probability of using P. polycephalum macroplasmodium for toxicity studies at the single-cell level, indicating that nTiO 2 could induce oxidative stress or damage in P. polycephalum even under dark conditions and suggesting that the release of nTiO 2 could lead to a growth imbalance of slime molds in the environment.

Oxidative damage and antioxidant defense in Caiman latirostris (Broad-snouted caiman) exposed in ovo to pesticide formulations.

PubMed

Burella, P M; Odetti, L M; Simoniello, M F; Poletta, G L

2018-06-13

The surface used for agricultural production in Argentina significantly increased in recent years, mainly due to the expansion of soybean crops. As a result, the use of agrochemicals increased too. Many natural populations of Caiman latirostris (broad-snouted caiman) are affected by habitat fragmentation and the constant exposure to pesticides. This exposure could produce Reactive Oxygen Species. The negative imbalance between ROS generation and the capacity of the biological systems to eliminate the reactive intermediaries or avoid the damage is called Oxidative Stress. The aim of this study was to evaluate oxidative damage and antioxidant defense in C. latirostris hatchlings after in ovo exposure to widely used pesticide formulations. Embryos were exposed by topical exposure on the eggshell, from the beginning of incubation period, to sub-lethal concentrations of two glyphosate formulations: PanzerGold® (PANZ) and Roundup® Full II (RU): 500, 750, 1000 μg/egg; to the endosulfan (END) formulation Galgofan® and the cypermethrin (CYP) formulation Atanor®: 1, 10, 100, and 1000 μg/ egg. Blood samples were taken to all animals immediately after hatching for the application and comparison of the following oxidative stress biomarkers between the exposed groups and their respective controls: lipoperoxidation through thiobarbituric acid reactive substances (TBARS), DNA base oxidation through the modified comet assay, and the activities of Catalase (CAT) and Superoxide dismutase (SOD) in erythrocytes. Our results showed lipoperoxidation in caiman exposed to END (10, 100, 1000 µg/egg), CYP (1, 10, 1000 µg/egg), RU (500, 1000 µg/egg) and PANZ (500, 1000 µg/egg), DNA base oxidation in those exposed to END (10, 100, 1000 µg/egg), CYP (1, 10 µg/egg) and PANZ (500, 750 µg/egg) as well as alteration in the activity of SOD in END 1 µg/egg and CYP (10, 1000 µg/egg). This study demonstrated the incidence of oxidative stress in animals exposed to pesticide formulations widely used in agricultural activity associated mainly with soybean crops, and add further information to that previously reported about pesticide effects in this native reptile species. Copyright © 2018 Elsevier Inc. All rights reserved.

Sub-acute deltamethrin and fluoride toxicity induced hepatic oxidative stress and biochemical alterations in rats.

PubMed

Dubey, Nitin; Khan, Adil Mehraj; Raina, Rajinder

2013-09-01

The current study investigated the effects of deltamethrin, fluoride (F(-)) and their combination on the hepatic oxidative stress and consequent alterations in blood biochemical markers of hepatic damage in rats. Significant hepatic oxidative stress and hepatic damage were observed in the toxicant exposed groups. These changes were higher in the deltamethrin-F(-) co-exposure treatment group, depicting a positive interaction between the two chemicals.

Trypanocidal nitroimidazole derivatives: relationships among chemical structure and genotoxic activity.

PubMed

Buschini, Annamaria; Giordani, Federica; de Albuquerque, Cristina Northfleet; Pellacani, Claudia; Pelosi, Giorgio; Rossi, Carlo; Zucchi, Tânia Maria Araújo Domingues; Poli, Paola

2007-05-15

Human American trypanosomiasis is resurgent in Latin Americans, and new drugs are urgently required as current medications suffer from a number of drawbacks. Some nitroheterocycles have been demonstrated to exert a potent activity against trypanosomes. However, host toxicity issues halted their development as trypanocides. As part of the efforts to develop new compounds in order to treat parasitic infections, it is important to define their structure-activity relationship. In this study, 5-nitromegazol and two of its analogues, 4-nitromegazol, and 1-methyl-5-nitro-2-imidazolecarboxaldehyde 5-nitroimidazole-thiosemicarbazone, were tested and compared for in vitro induction of DNA damage in human leukocytes by the comet assay, performed at different pHs to better identify the types of damage. Specific oxidatively generated damage to DNA was also measured by using the comet assay with endonucleases. DNA damage was found in 5-nitromegazol-treated cells: oxidative stress appeared as the main source of DNA damage. 4-Nitromegazol did not produce any significant effect, thus confirming that 4-nitroimidazoles isomers have no important biological activity. The 5-nitroimidazole-thiosemicarbazone induced DNA damage with a higher efficiency than 5-nitromegazol. The central role in the reduction process played by the acidic hydrazine proton present in the thiosemicarbazone group but not in the cyclic (thiadiazole) form can contribute to rationalise our results. Given its versatility, thiosemicarbazone moiety could be involved in different reactions with nitrogenous bases (nucleophilic and/or electrophilic attacks).

Dietary supplementation with the microalga Galdieria sulphuraria (Rhodophyta) reduces prolonged exercise-induced oxidative stress in rat tissues.

PubMed

Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Pollio, Antonino; Venditti, Paola

2015-01-01

We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion.

Spectroellipsometric detection of silicon substrate damage caused by radiofrequency sputtering of niobium oxide

NASA Astrophysics Data System (ADS)

Lohner, Tivadar; Serényi, Miklós; Szilágyi, Edit; Zolnai, Zsolt; Czigány, Zsolt; Khánh, Nguyen Quoc; Petrik, Péter; Fried, Miklós

2017-11-01

Substrate surface damage induced by deposition of metal atoms by radiofrequency (rf) sputtering or ion beam sputtering onto single-crystalline silicon (c-Si) surface has been characterized earlier by electrical measurements. The question arises whether it is possible to characterize surface damage using spectroscopic ellipsometry (SE). In our experiments niobium oxide layers were deposited by rf sputtering on c-Si substrates in gas mixture of oxygen and argon. Multiple angle of incidence spectroscopic ellipsometry measurements were performed, a four-layer optical model (surface roughness layer, niobium oxide layer, native silicon oxide layer and ion implantation-amorphized silicon [i-a-Si] layer on a c-Si substrate) was created in order to evaluate the spectra. The evaluations yielded thicknesses of several nm for the i-a-Si layer. Better agreement could be achieved between the measured and the generated spectra by inserting a mixed layer (with components of c-Si and i-a-Si applying the effective medium approximation) between the silicon oxide layer and the c-Si substrate. High depth resolution Rutherford backscattering (RBS) measurements were performed to investigate the interface disorder between the deposited niobium oxide layer and the c-Si substrate. Atomic resolution cross-sectional transmission electron microscopy investigation was applied to visualize the details of the damaged subsurface region of the substrate.

Role of oxidative stress in diabetic retinopathy and the beneficial effects of flavonoids.

PubMed

Ola, Mohammad Shamsul; Al-Dosari, Dalia; Alhomida, Abdullah S

2018-05-15

Diabetic retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious changes through dysregulation of cellular physiology that damages both neuronal and vascular cells. Here in this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contributes to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by us and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the potential beneficial effects of the six major flavonoid families, such as flavonones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flanonoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in the diabetic retina. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues

PubMed Central

Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Venditti, Paola

2015-01-01

We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. PMID:25874021

Synergistic antibacterial effects of localized heat and oxidative stress caused by hydroxyl radicals mediated by graphene/iron oxide-based nanocomposites.

PubMed

Pan, Wen-Yu; Huang, Chieh-Cheng; Lin, Tzu-Tsen; Hu, Hsin-Yi; Lin, Wei-Chih; Li, Meng-Ju; Sung, Hsing-Wen

2016-02-01

This work develops a composite system of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) that can synergistically induce physical and chemical damage to methicillin-resistant Staphylococcus aureus (MRSA) that are present in subcutaneous abscesses. rGO-IONP was synthesized by the chemical deposition of Fe(2+)/Fe(3+) ions on nanosheets of rGO in aqueous ammonia. The antibacterial efficacy of the as-prepared rGO-IONP was evaluated in a mouse model with MRSA-infected subcutaneous abscesses. Upon exposure to a near-infrared laser in vitro, rGO-IONP synergistically generated localized heat and large amounts of hydroxyl radicals, which inactivated MRSA. The in vivo results reveal that combined treatment with localized heat and oxidative stress that is caused by hydroxyl radicals accelerated the healing of wounds associated with MRSA-infected abscesses. The above results demonstrate that an rGO-IONP nanocomposite system that can effectively inactivate multiple-drug-resistant bacteria in subcutaneous infections was successfully developed. The emergence of methicillin-resistant S. aureus (MRSA) has posed a significant problem in the clinical setting. Thus, it is imperative to develop new treatment strategies against this. In this study, the authors described the use of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) to induce heat and chemical damage to MRSA. This approach may provide a platform the design of other treatment modalities against multiple-drug-resistant bacteria. Copyright © 2015 Elsevier Inc. All rights reserved.

Neil2-null Mice Accumulate Oxidized DNA Bases in the Transcriptionally Active Sequences of the Genome and Are Susceptible to Innate Inflammation* ♦

PubMed Central

Chakraborty, Anirban; Wakamiya, Maki; Venkova-Canova, Tatiana; Pandita, Raj K.; Aguilera-Aguirre, Leopoldo; Sarker, Altaf H.; Singh, Dharmendra Kumar; Hosoki, Koa; Wood, Thomas G.; Sharma, Gulshan; Cardenas, Victor; Sarkar, Partha S.; Sur, Sanjiv; Pandita, Tej K.; Boldogh, Istvan; Hazra, Tapas K.

2015-01-01

Why mammalian cells possess multiple DNA glycosylases (DGs) with overlapping substrate ranges for repairing oxidatively damaged bases via the base excision repair (BER) pathway is a long-standing question. To determine the biological role of these DGs, null animal models have been generated. Here, we report the generation and characterization of mice lacking Neil2 (Nei-like 2). As in mice deficient in each of the other four oxidized base-specific DGs (OGG1, NTH1, NEIL1, and NEIL3), Neil2-null mice show no overt phenotype. However, middle-aged to old Neil2-null mice show the accumulation of oxidative genomic damage, mostly in the transcribed regions. Immuno-pulldown analysis from wild-type (WT) mouse tissue showed the association of NEIL2 with RNA polymerase II, along with Cockayne syndrome group B protein, TFIIH, and other BER proteins. Chromatin immunoprecipitation analysis from mouse tissue showed co-occupancy of NEIL2 and RNA polymerase II only on the transcribed genes, consistent with our earlier in vitro findings on NEIL2's role in transcription-coupled BER. This study provides the first in vivo evidence of genomic region-specific repair in mammals. Furthermore, telomere loss and genomic instability were observed at a higher frequency in embryonic fibroblasts from Neil2-null mice than from the WT. Moreover, Neil2-null mice are much more responsive to inflammatory agents than WT mice. Taken together, our results underscore the importance of NEIL2 in protecting mammals from the development of various pathologies that are linked to genomic instability and/or inflammation. NEIL2 is thus likely to play an important role in long term genomic maintenance, particularly in long-lived mammals such as humans. PMID:26245904

G-Quadruplex Folds of the Human Telomere Sequence Alter the Site Reactivity and Reaction Pathway of Guanine Oxidation Compared to Duplex DNA

PubMed Central

Fleming, Aaron M.; Burrows, Cynthia J.

2013-01-01

Telomere shortening occurs during oxidative and inflammatory stress with guanine (G) as the major site of damage. In this work, a comprehensive profile of the sites of oxidation and structures of products observed from G-quadruplex and duplex structures of the human telomere sequence was studied in the G-quadruplex folds (hybrid (K+), basket (Na+), and propeller (K+ + 50% CH3CN)) resulting from the sequence 5’-(TAGGGT)4T-3’ and in an appropriate duplex containing one telomere repeat. Oxidations with four oxidant systems consisting of riboflavin photosensitization, carbonate radical generation, singlet oxygen, and the copper Fenton-like reaction were analyzed under conditions of low product conversion to determine relative reactivity. The one-electron oxidants damaged the 5’-G in G-quadruplexes leading to spiroiminodihydantoin (Sp) and 2,2,4-triamino-2H-oxazol-5-one (Z) as major products as well as 8-oxo-7,8-dihydroguanine (OG) and 5-guanidinohydantoin (Gh) in low relative yields, while oxidation in the duplex context produced damage at the 5’- and middle-Gs of GGG sequences and resulted in Gh being the major product. Addition of the reductant N-acetylcysteine (NAC) to the reaction did not alter the riboflavin-mediated damage sites, but decreased Z by 2-fold and increased OG by 5-fold, while not altering the hydantoin ratio. However, NAC completely quenched the CO3•− reactions. Singlet oxygen oxidations of the G-quadruplex showed reactivity at all Gs on the exterior faces of G-quartets and furnished the product Sp, while no oxidation was observed in the duplex context under these conditions, and addition of NAC had no effect. Because a long telomere sequence would have higher-order structures of G-quadruplexes, studies were also conducted with 5’-(TAGGGT)8-T-3’, and it provided similar oxidation profiles to the single G-quadruplex. Lastly, CuII/H2O2-mediated oxidations were found to be indiscriminate in the damage patterns, and 5-carboxamido-5-formamido-2-iminohydantoin (2Ih) was found to be a major duplex product, while nearly equal yields of 2Ih and Sp were observed in G-quadruplex contexts. These findings indicate that the nature of the secondary structure of folded DNA greatly alters both the reactivity of G toward oxidative stress as well as the product outcome and suggest that recognition of damage in telomeric sequences by repair enzymes may be profoundly different from that of B-form duplex DNA. PMID:23438298

Redox signaling is an early event in the pathogenesis of renovascular hypertension.

PubMed

Hartono, Stella P; Knudsen, Bruce E; Zubair, Adeel S; Nath, Karl A; Textor, Stephen J; Lerman, Lilach O; Grande, Joseph P

2013-09-10

Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3⁺ T cells and F4/80⁺ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

Cellular Responses in Human Dental Pulp Stem Cells Treated with Three Endodontic Materials

PubMed Central

Ibañez-Cabellos, José Santiago; de Cutanda, Sergio Bañuls-Sánchez; Berenguer-Pascual, Ester; Beltrán-García, Jesús; García-López, Eva; Pallardó, Federico V.; García-Giménez, José Luis; Pallarés-Sabater, Antonio; Zarzosa-López, Ignacio; Monterde, Manuel

2017-01-01

Human dental pulp stem cells (HDPSCs) are of special relevance in future regenerative dental therapies. Characterizing cytotoxicity and genotoxicity produced by endodontic materials is required to evaluate the potential for regeneration of injured tissues in future strategies combining regenerative and root canal therapies. This study explores the cytotoxicity and genotoxicity mediated by oxidative stress of three endodontic materials that are widely used on HDPSCs: a mineral trioxide aggregate (MTA-Angelus white), an epoxy resin sealant (AH-Plus cement), and an MTA-based cement sealer (MTA-Fillapex). Cell viability and cell death rate were assessed by flow cytometry. Oxidative stress was measured by OxyBlot. Levels of antioxidant enzymes were evaluated by Western blot. Genotoxicity was studied by quantifying the expression levels of DNA damage sensors such as ATM and RAD53 genes and DNA damage repair sensors such as RAD51 and PARP-1. Results indicate that AH-Plus increased apoptosis, oxidative stress, and genotoxicity markers in HDPSCs. MTA-Fillapex was the most cytotoxic oxidative stress inductor and genotoxic material for HDPSCs at longer times in preincubated cell culture medium, and MTA-Angelus was less cytotoxic and genotoxic than AH-Plus and MTA-Fillapex at all times assayed. PMID:28751918

Plant Flavone Apigenin Binds to Nucleic Acid Bases and Reduces Oxidative DNA Damage in Prostate Epithelial Cells

PubMed Central

Bhaskaran, Natarajan; Gupta, Sanjay

2014-01-01

Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it’s binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2′ deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities. PMID:24614817

Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells.

PubMed

Sharma, Haripaul; Kanwal, Rajnee; Bhaskaran, Natarajan; Gupta, Sanjay

2014-01-01

Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it's binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2' deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities.

Discussion of "Investigation of Oxide Bifilms in Investment Cast Superalloy IN100 Parts I and II"*

NASA Astrophysics Data System (ADS)

Campbell, John

2017-10-01

Fuchs and Kaplan carried out experiments in an attempt to ascertain whether oxide bifilms were present in a vacuum-cast Ni-base superalloy but concluded negatively. Although this author challenged their interpretation of their findings, both parties had overlooked the presence in the alloy of boron which is now known to inhibit bifilm formation. However, even though boron can help significantly, improved filling system designs remain important if other damaging entrainment defects are to be avoided.

Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder.

PubMed

Czarny, Piotr; Kwiatkowski, Dominik; Toma, Monika; Gałecki, Piotr; Orzechowska, Agata; Bobińska, Kinga; Bielecka-Kowalska, Anna; Szemraj, Janusz; Berk, Michael; Anderson, George; Śliwiński, Tomasz

2016-11-20

BACKGROUND Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins. MATERIAL AND METHODS Using TaqMan, we selected and genotyped the following SNPs: c.-441G>A (rs174538) of FEN1, c.2285T>C (rs1136410) of PARP1, c.580C>T (rs1799782) and c.1196A>G (rs25487) of XRCC1, c.*83A>C (rs4796030) and c.*50C>T (rs1052536) of LIG3, c.-7C>T (rs20579) of LIG1, and c.-468T>G (rs1760944) and c.444T>G (rs1130409) of APEX1 in 599 samples (288 rDD patients and 311 controls). RESULTS We found a strong correlation between rDD and both SNPs of LIG3, their haplotypes, as well as a weaker association with the c.-468T>G of APEXI which diminished after Nyholt correction. Polymorphisms of LIG3 were also associated with early onset versus late onset depression, whereas the c.-468T>G polymorphism showed the opposite association. CONCLUSIONS The SNPs of genes involved in the repair of oxidative DNA damage may modulate rDD risk. Since this is an exploratory study, the results should to be treated with caution and further work needs to be done to elucidate the exact involvement of DNA damage and repair mechanisms in the development of this disease.

Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder

PubMed Central

Czarny, Piotr; Kwiatkowski, Dominik; Toma, Monika; Gałecki, Piotr; Orzechowska, Agata; Bobińska, Kinga; Bielecka-Kowalska, Anna; Szemraj, Janusz; Berk, Michael; Anderson, George; Śliwiński, Tomasz

2016-01-01

Background Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins. Material/Methods Using TaqMan, we selected and genotyped the following SNPs: c.-441G>A (rs174538) of FEN1, c.2285T>C (rs1136410) of PARP1, c.580C>T (rs1799782) and c.1196A>G (rs25487) of XRCC1, c.*83A>C (rs4796030) and c.*50C>T (rs1052536) of LIG3, c.-7C>T (rs20579) of LIG1, and c.-468T>G (rs1760944) and c.444T>G (rs1130409) of APEX1 in 599 samples (288 rDD patients and 311 controls). Results We found a strong correlation between rDD and both SNPs of LIG3, their haplotypes, as well as a weaker association with the c.-468T>G of APEXI which diminished after Nyholt correction. Polymorphisms of LIG3 were also associated with early onset versus late onset depression, whereas the c.-468T>G polymorphism showed the opposite association. Conclusions The SNPs of genes involved in the repair of oxidative DNA damage may modulate rDD risk. Since this is an exploratory study, the results should to be treated with caution and further work needs to be done to elucidate the exact involvement of DNA damage and repair mechanisms in the development of this disease. PMID:27866211

Forecasting of the performance of MOS device for space applications

NASA Technical Reports Server (NTRS)

Fang, P. H.

1971-01-01

Analysis of radiation damage of MOSFET data from Explorer 34 (IMP-F), and radiation damage characteristics of MOSFET with boron diffused between a silicon semiconductor and silicon oxide are considered. The first subject is an interpretation of the discrepancy between the space data and the laboratory data. The second subject is an attempt to analyze the radiation damage characteristic of MOSFET when there is modification of electrical properties in the gate oxide region.

The protective effect of grape seed procyanidin extract against cadmium-induced renal oxidative damage in mice.

PubMed

Chen, Qing; Zhang, Rong; Li, Wei-min; Niu, Yu-jie; Guo, Hui-cai; Liu, Xue-hui; Hou, Yu-chun; Zhao, Li-juan

2013-11-01

As an important environmental pollutant, cadmium (Cd) can lead to serious renal damage. Grape seed procyanidins extract (GSPE), a biological active component of grape seed, has been shown to possess antioxidative effects. Here, we assessed the protective effect of GSPE on Cd-induced renal damage using animal experiment. After 30 days, the oxidative damage of kidney was evaluated through measurement of superoxide dismutase (SOD), glutathione peroxidation (GSH-Px) and malondialdehyde (MDA). Since, oxidative stress could lead to apoptosis, the renal apoptosis was measured using flow cytometer. Moreover, the expression of apoptosis-related protein Bax and Bcl-2 was analyzed by immunohistochemistry and Western blot. The results showed that Cd led to the decrease of SOD and GSH-Px activities, and the increase of MDA level, induced renal apoptosis. However, the coadministration of GSPE attenuated Cd-induced lipid peroxidation, and antagonized renal apoptosis, probably associated with the expression of Bax and Bcl-2. These data suggested that GSPE has protective effect against renal oxidative damage induced by Cd, which provide a potential natural chemopreventive agent against Cd-poisoning. Copyright © 2013 Elsevier B.V. All rights reserved.

Amelioration of oxidative DNA damage in mouse peritoneal macrophages by Hippophae salicifolia due to its proton (H+) donation capability: Ex vivo and in vivo studies

PubMed Central

Chakraborty, Mainak; Karmakar, Indrajit; Haldar, Sagnik; Das, Avratanu; Bala, Asis; Haldar, Pallab Kanti

2016-01-01

Introduction: The present study evaluates the antioxidant effect of methanol extract of Hippophae salicifolia (MEHS) bark with special emphasis on its role on oxidative DNA damage in mouse peritoneal macrophages. Material and Methods: In vitro antioxidant activity was estimated by standard antioxidant assays whereas the antioxidant activity concluded the H+ donating capacity. Mouse erythrocytes’ hemolysis and peritoneal macrophages’ DNA damage were determined spectrophotometrically. In vivo antioxidant activity of MEHS was determined in carbon tetrachloride-induced mice by studying its effect on superoxide anion production in macrophages cells, superoxide dismutase in the cell lysate, DNA damage, lipid peroxidation, and reduces glutathione. Results: The extract showed good in vitro antioxidant activities whereas the inhibitory concentrations values ranged from 5.80 to 106.5 μg/ml. MEHS significantly (P < 0.05) attenuated the oxidative DNA damage. It also attenuated the oxidative conversion of hemoglobin to methemoglobin and elevation of enzymatic and nonenzymatic antioxidant in cells. Conclusion: The result indicates MEHS has good in vitro-in vivo antioxidant property as well as the protective effect on DNA and red blood cell may be due to its H+ donating property. PMID:27413349

Cisplatin and Aminoglycoside Antibiotics: Hearing Loss and Its Prevention

PubMed Central

Schacht, Jochen; Talaska, Andra E.; Rybak, Leonard P.

2013-01-01

This review introduces the pathology of aminoglycoside antibiotic and the cisplatin chemotherapy classes of drugs, discusses oxidative stress in the inner ear as a primary trigger for cell damage, and delineates the ensuing cell death pathways. Among potentially ototoxic (damaging the inner ear) therapeutics, the platinum-based anti-cancer drugs and the aminoglycoside antibiotics are of critical clinical importance. Both drugs cause sensorineural hearing loss in patients, a side effect that can be reproduced in experimental animals. Hearing loss is reflected primarily in damage to outer hair cells, beginning in the basal turn of the cochlea. In addition, aminoglycosides might affect the vestibular system while cisplatin seems to have a much lower likelihood to do so. Finally, based on an understanding the mechanisms of ototoxicity pharmaceutical ways of protection of the cochlea are presented PMID:23045231

Oxidative Damage Induced by Arsenic in Mice or Rats: A Systematic Review and Meta-Analysis.

PubMed

Xu, Mengchuan; Rui, Dongsheng; Yan, Yizhong; Xu, Shangzhi; Niu, Qiang; Feng, Gangling; Wang, Yan; Li, Shugang; Jing, Mingxia

2017-03-01

In this meta-analysis, studies reporting arsenic-induced oxidative damage in mouse models were systematically evaluated to provide a scientific understanding of oxidative stress mechanisms associated with arsenic poisoning. Fifty-eight relevant peer-reviewed publications were identified through exhaustive database searching. Oxidative stress indexes assessed included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR), oxidized glutathione (GSSG), malondialdehyde (MDA), and reactive oxygen species (ROS). Our meta-analysis showed that arsenic exposure generally suppressed measured levels of the antioxidants, SOD, CAT, GSH, GPx, GST, and GR, but increased levels of the oxidants, GSSG, MDA, and ROS. Arsenic valence was important and GR and MDA levels increased to a significantly (P < 0.05) greater extent upon exposure to As 3+ than to As 5+ . Other factors that contributed to a greater overall oxidative effect from arsenic exposure included intervention time, intervention method, dosage, age of animals, and the sample source from which the indexes were estimated. Our meta-analysis effectively summarized a wide range of studies and detected a positive relationship between arsenic exposure and oxidative damage. These data provide a scientific basis for the prevention and treatment of arsenic poisoning.

Effect of prolonged exercise on oxidative damage and susceptibility to oxidants of rat tissues in severe hyperthyroidism.

PubMed

Venditti, P; De Rosa, R; Caldarone, G; Di Meo, S

2005-10-15

We investigated effects of prolonged aerobic exercise and severe hyperthyroidism on indices of oxidative damage, susceptibility to oxidants, and respiratory capacity of homogenates from rat liver, heart and skeletal muscle. Both treatments induced increases in hydroperoxide and protein-bound carbonyl levels. Moreover, the highest increases were found when hyperthyroid animals were subjected to exercise. These changes, which were associated to reduced exercise endurance capacity, were in part due to higher susceptibility to oxidants of hyperthyroid tissues. Levels of oxidative damage indices were scarcely related to changes in antioxidant enzyme activities and lipid-soluble antioxidant concentrations. However, the finding that, following exercise the scavenger levels generally decreased in liver homogenates and increased in heart and muscles ones, suggested a net shuttle of antioxidants from liver to other tissues under need. Aerobic capacity, evaluated by cytochrome oxidase activity, was not modified by exercise, which, conversely, affected the rates of oxygen consumption of hyperthyroid preparations. These results seem to confirm the higher susceptibility of hyperthyroid tissues to oxidative challenge, because the mechanisms underlying the opposite changes in respiration rates during State 4 and State 3 likely involve oxidative modifications of components of mitochondrial respiratory chain, different from cytochrome aa3.

Yolk testosterone reduces oxidative damages during postnatal development

PubMed Central

Noguera, José Carlos; Alonso-Alvarez, Carlos; Kim, Sin-Yeon; Morales, Judith; Velando, Alberto

2011-01-01

Conditions experienced during early life can influence the development of an organism and several physiological traits, even in adulthood. An important factor is the level of oxidative stress experienced during early life. In birds, extra-genomic egg substances, such as the testosterone hormone, may exert a widespread influence over the offspring phenotype. Interestingly, testosterone can also upregulate the bioavailability of certain antioxidants but simultaneously increases the susceptibility to oxidative stress in adulthood. However, little is known about the effects of maternally derived yolk testosterone on oxidative stress in developing birds. Here, we investigated the role of yolk testosterone on oxidative stress of yellow-legged gull chicks during their early development by experimentally increasing yolk testosterone levels. Levels of antioxidants, reactive oxygen species and lipid oxidative damage were determined in plasma during nestlings' growth. Our results revealed that, contrary to control chicks, birds hatched from testosterone-treated eggs did not show an increase in the levels of oxidative damage during postnatal development. Moreover, the same birds showed a transient increase in plasma antioxidant levels. Our results suggest that yolk testosterone may shape the oxidative stress-resistance phenotype of the chicks during early development owing to an increase in antioxidant defences and repair processes. PMID:20659922

Consequences of acute oxidative stress in Leishmania amazonensis: From telomere shortening to the selection of the fittest parasites.

PubMed

da Silva, Marcelo Santos; Segatto, Marcela; Pavani, Raphael Souza; Gutierrez-Rodrigues, Fernanda; Bispo, Vanderson da Silva; de Medeiros, Marisa Helena Gennari; Calado, Rodrigo Tocantins; Elias, Maria Carolina; Cano, Maria Isabel Nogueira

2017-01-01

Leishmaniasis is a spectrum of diseases caused by parasites of the genus Leishmania that affects millions of people around the world. During infection, the parasites use different strategies to survive the host's defenses, including overcoming exposure to reactive oxidant species (ROS), responsible for causing damage to lipids, proteins and DNA. This damage especially affects telomeres, which frequently results in genome instability, senescence and cell death. Telomeres are the physical ends of the chromosomes composed of repetitive DNA coupled with proteins, whose function is to protect the chromosomes termini and avoid end-fusion and nucleolytic degradation. In this work, we induced acute oxidative stress in promastigote forms of Leishmania amazonensis by treating parasites with 2mM hydrogen peroxide (H 2 O 2 ) for 1h, which was able to increase intracellular ROS levels. In addition, oxidative stress induced DNA damage, as confirmed by 8-oxodGuo quantification and TUNEL assays and the dissociation of LaRPA-1 from the 3' G-overhang, leading to telomere shortening. Moreover, LaRPA-1 was observed to interact with newly formed C-rich single-stranded telomeric DNA, probably as a consequence of the DNA damage response. Nonetheless, acute oxidative stress caused the death of some of the L. amazonensis population and induced cell cycle arrest at the G2/M phase in survivor parasites, which were able to continue proliferating and replicating DNA and became more resistant to oxidative stress. Taken together, these results suggest that adaptation occurs through the selection of the fittest parasites in terms of repairing oxidative DNA damage at telomeres and maintaining genome stability in a stressful environment. Copyright © 2016 Elsevier B.V. All rights reserved.

The RNA surveillance protein SMG1 activates p53 in response to DNA double-strand breaks but not exogenously oxidized mRNA

PubMed Central

Gewandter, Jennifer S; Bambara, Robert A

2011-01-01

DNA damage, stalled replication forks, errors in mRNA splicing and availability of nutrients activate specific phosphatidylinositiol-3-kinase-like kinases (PIKKs) that in turn phosphorylate downstream targets such as p53 on serine 15. While the PIKK proteins ATM and ATR respond to specific DNA lesions, SMG1 responds to errors in mRNA splicing and when cells are exposed to genotoxic stress. Yet, whether genotoxic stress activates SMG1 through specific types of DNA lesions or RNA damage remains poorly understood. Here, we demonstrate that siRNA oligonucleotides targeting the mRNA surveillance proteins SMG1, Upf1, Upf2 or the PIKK protein ATM attenuated p53 (ser15) phosphorylation in cells damaged by high oxygen (hyperoxia), a model of persistent oxidative stress that damages nucleotides. In contrast, loss of SMG1 or ATM, but not Upf1 or Upf2 reduced p53 (ser15) phosphorylation in response to DNA double strand breaks produced by expression of the endonuclease I-PpoI. To determine whether SMG1-dependent activation of p53 was in response to oxidative mRNA damage, mRNA encoding green fluorescence protein (GFP) transcribed in vitro was oxidized by Fenton chemistry and transfected into cells. Although oxidation of GFP mRNA resulted in dose-dependent fragmentation of the mRNA and reduced expression of GFP, it did not stimulate p53 or the p53-target gene p21. These findings establish SMG1 activates p53 in response to DNA double strand breaks independent of the RNA surveillance proteins Upf1 or Upf2; however, these proteins can stimulate p53 in response to oxidative stress but not necessarily oxidized RNA. PMID:21701263

Mangiferin decreases inflammation and oxidative damage in rat brain after stress.

PubMed

Márquez, Lucía; García-Bueno, Borja; Madrigal, José L M; Leza, Juan C

2012-09-01

Stress exposure elicits neuroinflammation and oxidative damage in brain, and stress-related neurological and neuropsychiatric diseases have been associated with cell damage and death. Mangiferin (MAG) is a polyphenolic compound abundant in the stem bark of Mangifera indica L. with antioxidant and anti-inflammatory properties in different experimental settings. In this study, the capacity of MAG to prevent neuroinflammation and brain oxidative damage induced by stress exposure was investigated. Young-adult male Wistar rats immobilized during 6 h were administered by oral gavage with increasing doses of MAG (15, 30, and 60 mg/Kg), respectively, 7 days before stress. Prior treatment with MAG prevented all of the following stress-induced effects: (1) increase in glucocorticoids (GCs) and interleukin-1β (IL-1β) plasma levels, (2) loss of redox balance and reduction in catalase brain levels, (3) increase in pro-inflammatory mediators, such as tumor necrosis factor alpha TNF-α and its receptor TNF-R1, nuclear factor-kappa B (NF-κB) and synthesis enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), (4) increase in lipid peroxidation. These multifaceted protective effects suggest that MAG administration could be a new therapeutic strategy in neurological/neuropsychiatric pathologies in which hypothalamic/pituitary/adrenal (HPA) stress axis dysregulation, neuroinflammation, and oxidative damage take place in their pathophysiology.

Apigenin attenuates streptozotocin-induced pancreatic β cell damage by its protective effects on cellular antioxidant defense.

PubMed

Wang, Ning; Yi, Wen Jing; Tan, Lu; Zhang, Jia Hui; Xu, Jiamin; Chen, Yi; Qin, Mengting; Yu, Shuang; Guan, Jing; Zhang, Rui

2017-06-01

Pancreatic beta cells are very sensitive to oxidative stress, which is one of the major causes of cell damages in diabetes. Growing interest has focused on the development of effective therapeutics to protect pancreatic cells from oxidative stress and searching for potentially protective antioxidants for treating diabetes. Apigenin, a plant-derived flavonoid, was investigated to determine whether it could protect rat insulinoma cell lines (RINm5F pancreatic beta cells) against streptozotocin (STZ)-induced oxidative damages and the mechanisms implicated. Our results showed that STZ treatment could induce oxidative stress and consequent cytotoxic effects in RINm5F cells. Pretreatment with apigenin effectively decreased the intracellular reactive oxygen species (ROS) production, attenuated cellular DNA damage, diminished lipid peroxidation, relieved protein carbonylation, and restored the cell apoptosis of pancreatic beta cells stressed by STZ. Our further experiments demonstrated that the beneficial effects of apigenin were related to ameliorate the loss of antioxidant enzymes of the STZ-treated cells in the level of gene transcription, protein expression, and enzyme activity. That suggested apigenin was not only a free radical scavenger but also a regulator to antioxidant defenses of pancreatic cells. Taken all together, our findings suggested that apigenin could attenuate the STZ-induced oxidative damages in pancreatic beta cells and might serve as a novel agent for the treatment of diabetes.

DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea

PubMed Central

Jones, Daniel L.; Baxter, Bonnie K.

2017-01-01

Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV) radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately result in mutation and cell death. As such, these microorganisms have evolved a number of strategies to navigate the threat of DNA damage, which we differentiate into two categories: DNA repair and photoprotection. Photoprotection encompasses damage avoidance strategies that serve as a “first line of defense,” and in halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative damage avoidance, polyploidy, and genomic signatures that make DNA less susceptible to photodamage. Photolesions that do arise are addressed by a number of DNA repair mechanisms that halophilic archaea efficiently utilize, which include photoreactivation, nucleotide excision repair, base excision repair, and homologous recombination. This review seeks to place DNA damage, repair, and photoprotection in the context of halophilic archaea and the solar radiation of their hypersaline environments. We also provide new insight into the breadth of strategies and how they may work together to produce remarkable UV-resistance for these microorganisms. PMID:29033920

DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea.

PubMed

Jones, Daniel L; Baxter, Bonnie K

2017-01-01

Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV) radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately result in mutation and cell death. As such, these microorganisms have evolved a number of strategies to navigate the threat of DNA damage, which we differentiate into two categories: DNA repair and photoprotection. Photoprotection encompasses damage avoidance strategies that serve as a "first line of defense," and in halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative damage avoidance, polyploidy, and genomic signatures that make DNA less susceptible to photodamage. Photolesions that do arise are addressed by a number of DNA repair mechanisms that halophilic archaea efficiently utilize, which include photoreactivation, nucleotide excision repair, base excision repair, and homologous recombination. This review seeks to place DNA damage, repair, and photoprotection in the context of halophilic archaea and the solar radiation of their hypersaline environments. We also provide new insight into the breadth of strategies and how they may work together to produce remarkable UV-resistance for these microorganisms.

Effects of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites on DNA damage and repair under in vitro conditions.

PubMed

Ozcagli, Eren; Alpertunga, Buket; Fenga, Concettina; Berktas, Mehmet; Tsitsimpikou, Christina; Wilks, Martin F; Tsatsakis, Αristidis M

2016-03-01

3-monochloropropane-1,2-diol (3-MCPD) is a food contaminant that occurs during industrial production processes and can be found mainly in fat and salt containing products. 3-MCPD has exhibited mutagenic activity in vitro but not in vivo, however, a genotoxic mechanism for the occurrence of kidney tumors has not so far been excluded. The main pathway of mammalian 3-MCPD metabolism is via the formation of β--chlorolactatic acid and formation of glycidol has been demonstrated in bacterial metabolism. The aim of this study was to investigate genotoxic and oxidative DNA damaging effects of 3-MCPD and its metabolites, and to provide a better understanding of their roles in DNA repair processes. DNA damage was assessed by alkaline comet assay in target rat kidney epithelial cell lines (NRK-52E) and human embryonic kidney cells (HEK-293). Purine and pyrimidine base damage, H2O2 sensitivity and DNA repair capacity were assessed via modified comet assay. The results revealed in vitro evidence for increased genotoxicity and H2O2 sensitivity. No association was found between oxidative DNA damage and DNA repair capacity with the exception of glycidol treatment at 20 μg/mL. These findings provide further insights into the mechanisms underlying the in vitro genotoxic potential of 3-MCPD and metabolites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characteristics and oxidative stress on rats and traffic policemen of ambient fine particulate matter from Shenyang.

PubMed

Ma, Mingyue; Li, Shuyin; Jin, Huanrong; Zhang, Yumin; Xu, Jia; Chen, Dongmei; Kuimin, Chen; Yuan, Zhou; Xiao, Chunling

2015-09-01

Fine particulate matter (PM2.5) pollution is becoming serious in China. This study aimed to investigate the impact of PM2.5 on DNA damage in Shenyang city. The concentration and composition of PM2.5 in traffic policemen's working sites including fields and indoor offices were obtained. Blood samples of field and office policemen were collected to detect DNA damage by Comet assay. Rats were used to further analyzing the oxidative DNA damage. The average concentration of PM2.5 in exposed group was significantly higher than that in control group. Composition analysis revealed that toxic heavy metal and polycyclic aromatic hydrocarbon substances were main elements of this PM2.5. DNA damage in field policemen was significantly higher than those in non-field group. Moreover, animal studies confirmed the oxidative DNA damage induced by PM2.5. Taken together, high DNA damages are found in the Shenyang traffic policemen and rats exposed to high level of airborne PM2.5. Copyright © 2015 Elsevier B.V. All rights reserved.

Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

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

MacNaughton, W.K.; Wallace, J.L.; Cirino, G.

1989-01-01

The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area of 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protectivemore » effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanal administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 ug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol.« less

High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

PubMed

Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

2014-05-01

Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

In Vivo Alkaline Comet Assay and Enzyme-modified Alkaline Comet Assay for Measuring DNA Strand Breaks and Oxidative DNA Damage in Rat Liver

PubMed Central

Ding, Wei; Bishop, Michelle E.; Lyn-Cook, Lascelles E.; Davis, Kelly J.; Manjanatha, Mugimane G.

2016-01-01

Unrepaired DNA damage can lead to genetic instability, which in turn may enhance cancer development. Therefore, identifying potential DNA damaging agents is important for protecting public health. The in vivo alkaline comet assay, which detects DNA damage as strand breaks, is especially relevant for assessing the genotoxic hazards of xenobiotics, as its responses reflect the in vivo absorption, tissue distribution, metabolism and excretion (ADME) of chemicals, as well as DNA repair process. Compared to other in vivo DNA damage assays, the assay is rapid, sensitive, visual and inexpensive, and, by converting oxidative DNA damage into strand breaks using specific repair enzymes, the assay can measure oxidative DNA damage in an efficient and relatively artifact-free manner. Measurement of DNA damage with the comet assay can be performed using both acute and subchronic toxicology study designs, and by integrating the comet assay with other toxicological assessments, the assay addresses animal welfare requirements by making maximum use of animal resources. Another major advantage of the assays is that they only require a small amount of cells, and the cells do not have to be derived from proliferating cell populations. The assays also can be performed with a variety of human samples obtained from clinically or occupationally exposed individuals. PMID:27166647

In Vivo Alkaline Comet Assay and Enzyme-modified Alkaline Comet Assay for Measuring DNA Strand Breaks and Oxidative DNA Damage in Rat Liver.

PubMed

Ding, Wei; Bishop, Michelle E; Lyn-Cook, Lascelles E; Davis, Kelly J; Manjanatha, Mugimane G

2016-05-04

Unrepaired DNA damage can lead to genetic instability, which in turn may enhance cancer development. Therefore, identifying potential DNA damaging agents is important for protecting public health. The in vivo alkaline comet assay, which detects DNA damage as strand breaks, is especially relevant for assessing the genotoxic hazards of xenobiotics, as its responses reflect the in vivo absorption, tissue distribution, metabolism and excretion (ADME) of chemicals, as well as DNA repair process. Compared to other in vivo DNA damage assays, the assay is rapid, sensitive, visual and inexpensive, and, by converting oxidative DNA damage into strand breaks using specific repair enzymes, the assay can measure oxidative DNA damage in an efficient and relatively artifact-free manner. Measurement of DNA damage with the comet assay can be performed using both acute and subchronic toxicology study designs, and by integrating the comet assay with other toxicological assessments, the assay addresses animal welfare requirements by making maximum use of animal resources. Another major advantage of the assays is that they only require a small amount of cells, and the cells do not have to be derived from proliferating cell populations. The assays also can be performed with a variety of human samples obtained from clinically or occupationally exposed individuals.

The oxidative hypothesis of senescence.

PubMed

Gilca, M; Stoian, I; Atanasiu, V; Virgolici, B

2007-01-01

The oxidative hypothesis of senescence, since its origin in 1956, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. Age-increasing oxidative injuries induced by free radicals, higher susceptibility to oxidative stress in short-lived organisms, genetic manipulations that alter both oxidative resistance and longevity and the anti-ageing effect of caloric restriction and intermittent fasting are a few examples of accepted scientific facts that support the oxidative theory of senescence. Though not completely understood due to the complex "network" of redox regulatory systems, the implication of oxidative stress in the ageing process is now well documented. Moreover, it is compatible with other current ageing theories (e.g, those implicating the mitochondrial damage/mitochondrial-lysosomal axis, stress-induced premature senescence, biological "garbage" accumulation, etc). This review is intended to summarize and critically discuss the redox mechanisms involved during the ageing process: sources of oxidant agents in ageing (mitochondrial -electron transport chain, nitric oxide synthase reaction- and non-mitochondrial- Fenton reaction, microsomal cytochrome P450 enzymes, peroxisomal beta -oxidation and respiratory burst of phagocytic cells), antioxidant changes in ageing (enzymatic- superoxide dismutase, glutathione-reductase, glutathion peroxidase, catalase- and non-enzymatic glutathione, ascorbate, urate, bilirubine, melatonin, tocopherols, carotenoids, ubiquinol), alteration of oxidative damage repairing mechanisms and the role of free radicals as signaling molecules in ageing.

Redox-linked effects of green tea on DNA damage and repair, and influence of microsatellite polymorphism in HMOX-1: results of a human intervention trial.

PubMed

Choi, Siu-Wai; Yeung, Vincent T F; Collins, Andrew R; Benzie, Iris F F

2015-01-01

Green tea has many reported health benefits, including genoprotective and antioxidant effects, but green tea has pro-oxidant activity in vitro. A tea-induced pro-oxidant shift that triggers cytoprotective adaptations has been postulated, but human data are lacking. We investigated effects on oxidation-induced DNA damage and redox-linked cytoprotective factors, including 8-oxoguanine glycosylase (hOGG1) and heme oxygenase 1 (HMOX-1) in lymphocytes in a randomised, placebo-controlled, cross-over supplementation trial. hOGG1 catalyses the first step in base excision repair; increased HMOX-1 is a sign of cytoprotective response to pro-oxidant change. The influence of microsatellite polymorphisms in the HMOX-1 promoter region was also explored. Higher numbers of GT repeats [GT(n)] in this region reportedly diminish response to pro-oxidant change. Green tea [2 × 150 ml of 1% w/v tea/day (or water as control)] was taken for 12 weeks by 43 Type 2 diabetes subjects {20 with short [S/S; GT(n) < 25] and 23 with long [L/L; GT(n) ≥ 25]}. Fasting venous blood was collected before and after each treatment. The formamidopyrimidine DNA glycosylase-assisted comet assay was used to measure DNA damage in lymphocytes. For measuring hOGG1 activity, we used photo-damaged HeLa cells incubated with lymphocyte extracts from test subjects, in combination with the comet assay. Lymphocyte HMOX-1 and hOGG1 protein concentrations and expression (mRNA) of redox-sensitive genes, including HMOX-1 and hOGG1, were also investigated. Results showed significantly (P < 0.01) lower (~15%) DNA damage, higher (~50%) hOGG1 activity and higher (~40%) HMOX-1 protein concentration after tea. No changes in mRNA expression were seen. Baseline HMOX-1 protein and hOGG1 activity were higher (P < 0.05) in the S/S group, but tea-associated responses were similar in both GT(n) groups. Green tea is clearly associated with lowered DNA damage, increased hOGG1 activity and higher HMOX-1 protein levels. Further study is needed to confirm a cause and effect relationship and to establish if these effects are mediated by post-translational changes in proteins or by increased gene expression. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The damage equivalence of electrons, protons, alphas and gamma rays in rad-hard MOS devices

NASA Technical Reports Server (NTRS)

Stassinopoulos, E. G.; Van Gunten, O.; Brucker, G. J.; Knudson, A. R.; Jordan, T. M.

1983-01-01

This paper reports on a study of damage equivalence in rad-hard MOS devices with 100,000 rads (SiO2) capability. Damage sensitivities for electrons of 1, 2, 3, 5, and 7 MeV, protons of 1, 3, 7, 22, and 40 MeV, 3.4-MeV alphas, and Co-60 gammas were measured and compared. Results indicated that qualitatively the same charge recombination effects occurred in hard oxide devices for doses of 100,000 rads (SiO2) as in soft oxide parts for doses of 1 to 4 krads (SiO2). Consequently, damage equivalency or non-equivalency depended on radiation type and energy. However, recovery effects, both during and after irradiation, controlled relative damage sensitivity and its dependency on total dose, dose rate, supply bias, gate bias, radiation type, and energy. Correction factors can be derived from these data or from similar tests of other hard oxide type, so as to properly evaluate the combined effects of the total space environment.

Microcarbon-based facial creams activate aerial oxygen under light to reactive oxygen species damaging cell

NASA Astrophysics Data System (ADS)

Maity, Sheli; Pakhira, Bholanath; Ghosh, Subrata; Saha, Royina; Sarkar, Ripon; Barui, Ananya; Sarkar, Sabyasachi

2017-11-01

Nanosized reduced graphene oxide (rGO) is found in active microcarbon used in popular face cream from the manufacturers like Ponds, Nevia, and Garnier which, under visible light exposure, gets activated by aerial oxygen to generate reactive oxygen species (ROS) harmful to skin.

Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats.

PubMed

Garnacho-Castaño, Manuel Vicente; Alva, Norma; Sánchez-Nuño, Sergio; Bardallo, Raquel G; Palomeque, Jesús; Carbonell, Teresa

2016-12-01

Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O 2 ), one kept at normothermia (HN) (37 °C) and the other under deep hypothermia (HH) (central body temperature of 21-22 °C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia.

An evaluation method of the profile of plasma-induced defects based on capacitance-voltage measurement

NASA Astrophysics Data System (ADS)

Okada, Yukimasa; Ono, Kouichi; Eriguchi, Koji

2017-06-01

Aggressive shrinkage and geometrical transition to three-dimensional structures in metal-oxide-semiconductor field-effect transistors (MOSFETs) lead to potentially serious problems regarding plasma processing such as plasma-induced physical damage (PPD). For the precise control of material processing and future device designs, it is extremely important to clarify the depth and energy profiles of PPD. Conventional methods to estimate the PPD profile (e.g., wet etching) are time-consuming. In this study, we propose an advanced method using a simple capacitance-voltage (C-V) measurement. The method first assumes the depth and energy profiles of defects in Si substrates, and then optimizes the C-V curves. We applied this methodology to evaluate the defect generation in (100), (111), and (110) Si substrates. No orientation dependence was found regarding the surface-oxide layers, whereas a large number of defects was assigned in the case of (110). The damaged layer thickness and areal density were estimated. This method provides the highly sensitive PPD prediction indispensable for designing future low-damage plasma processes.

Quantitative proteomics of synaptic and nonsynaptic mitochondria: insights for synaptic mitochondrial vulnerability.

PubMed

Stauch, Kelly L; Purnell, Phillip R; Fox, Howard S

2014-05-02

Synaptic mitochondria are essential for maintaining calcium homeostasis and producing ATP, processes vital for neuronal integrity and synaptic transmission. Synaptic mitochondria exhibit increased oxidative damage during aging and are more vulnerable to calcium insult than nonsynaptic mitochondria. Why synaptic mitochondria are specifically more susceptible to cumulative damage remains to be determined. In this study, the generation of a super-SILAC mix that served as an appropriate internal standard for mouse brain mitochondria mass spectrometry based analysis allowed for the quantification of the proteomic differences between synaptic and nonsynaptic mitochondria isolated from 10-month-old mice. We identified a total of 2260 common proteins between synaptic and nonsynaptic mitochondria of which 1629 were annotated as mitochondrial. Quantitative proteomic analysis of the proteins common between synaptic and nonsynaptic mitochondria revealed significant differential expression of 522 proteins involved in several pathways including oxidative phosphorylation, mitochondrial fission/fusion, calcium transport, and mitochondrial DNA replication and maintenance. In comparison to nonsynaptic mitochondria, synaptic mitochondria exhibited increased age-associated mitochondrial DNA deletions and decreased bioenergetic function. These findings provide insights into synaptic mitochondrial susceptibility to damage.

Quantitative Proteomics of Synaptic and Nonsynaptic Mitochondria: Insights for Synaptic Mitochondrial Vulnerability

PubMed Central

2015-01-01

Synaptic mitochondria are essential for maintaining calcium homeostasis and producing ATP, processes vital for neuronal integrity and synaptic transmission. Synaptic mitochondria exhibit increased oxidative damage during aging and are more vulnerable to calcium insult than nonsynaptic mitochondria. Why synaptic mitochondria are specifically more susceptible to cumulative damage remains to be determined. In this study, the generation of a super-SILAC mix that served as an appropriate internal standard for mouse brain mitochondria mass spectrometry based analysis allowed for the quantification of the proteomic differences between synaptic and nonsynaptic mitochondria isolated from 10-month-old mice. We identified a total of 2260 common proteins between synaptic and nonsynaptic mitochondria of which 1629 were annotated as mitochondrial. Quantitative proteomic analysis of the proteins common between synaptic and nonsynaptic mitochondria revealed significant differential expression of 522 proteins involved in several pathways including oxidative phosphorylation, mitochondrial fission/fusion, calcium transport, and mitochondrial DNA replication and maintenance. In comparison to nonsynaptic mitochondria, synaptic mitochondria exhibited increased age-associated mitochondrial DNA deletions and decreased bioenergetic function. These findings provide insights into synaptic mitochondrial susceptibility to damage. PMID:24708184

Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.

PubMed

Cafueri, Giuseppe; Parodi, Federica; Pistorio, Angela; Bertolotto, Maria; Ventura, Francesco; Gambini, Claudio; Bianco, Paolo; Dallegri, Franco; Pistoia, Vito; Pezzolo, Annalisa; Palombo, Domenico

2012-01-01

Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG). Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.