WorldWideScience

Sample records for production oxidative damage

  1. Bilirubin and its oxidation products damage brain white matter

    Science.gov (United States)

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-01-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  2. Bee products prevent agrichemical-induced oxidative damage in fish.

    Directory of Open Access Journals (Sweden)

    Daiane Ferreira

    Full Text Available In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™ and a group that was exposed to 0.88 mg L(-1 of TEB alone (corresponding to 16.6% of the 96-h LC50. We show that waterborne bee products, including royal jelly (RJ, honey (H, bee pollen (BP and propolis (P, reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD, catalase (CAT and glutathione-S-transferase (GST are increased.

  3. Bee products prevent agrichemical-induced oxidative damage in fish.

    Science.gov (United States)

    Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; da Rosa, João Gabriel Santos; Gusso, Darlan; Oliveira, Thiago Acosta; de Abreu, Murilo Sander; Barcellos, Leonardo José Gil

    2013-01-01

    In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g) were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™) and a group that was exposed to 0.88 mg L(-1) of TEB alone (corresponding to 16.6% of the 96-h LC50). We show that waterborne bee products, including royal jelly (RJ), honey (H), bee pollen (BP) and propolis (P), reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) are increased.

  4. Epiphytes modulate Posidonia oceanica photosynthetic production, energetic balance, antioxidant mechanisms and oxidative damage

    Directory of Open Access Journals (Sweden)

    Monya Mendes Costa

    2015-12-01

    Full Text Available Epiphytes impose physical barriers to light penetration into seagrass leaves causing shading, which may decrease the production of oxygen reactive species (ROS, but also constitute a physical aggression that may trigger the production of ROS, leading to oxidative damage. Here we investigate the effects of epiphytes on Posidonia oceanica under both interactive perspectives, light attenuation and oxidative stress. Specifically the role of epiphytes in net photosynthesis, chlorophyll a and b, photoprotection (Violaxanthin+Anteraxanthin+Zeaxanthin cycle, soluble sugar and starch contents, enzymatic (ascorbate peroxidase (APX and dehydroascorbate reductase (DHAR and global (trolox equivalent antioxidant capacity (TEAC and oxygen radical antioxidant capacity (ORAC antioxidant responses, phenolics and oxidative damage (malondialdehyde are tested. Leaves with epiphytes showed higher chlorophyll b and lower content in VAZ cycle carotenoids. Epiphyte shading was the probable reason for the lower VAZ de-epoxidation-ratio of leaves with epiphytes. In spite of being shaded, leaves with epiphytes showed higher antioxidant levels, indicating that epiphytes trigger the production of ROS. Both ORAC and TEAC and also APX and DHAR activities were higher in leaves with epiphytes, indicating that this response was related with its presence. Malondialdehyde concentrations also suggest oxidative damage caused by epiphytes. We conclude that the epiphyte load causes oxidative stress in P. oceanica and the mechanisms to scavenge ROS were not completely effective to avoid cell damage.

  5. Inhibition of myeloperoxidase oxidant production by N-acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke.

    Science.gov (United States)

    Yu, Guoliang; Liang, Ye; Huang, Ziming; Jones, Deron W; Pritchard, Kirkwood A; Zhang, Hao

    2016-05-24

    Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. To determine if and the extent to which MPO-generated oxidants contribute to brain I/R injury, we treated mice subjected to middle cerebral artery occlusion (MCAO) with N-acetyl lysyltyrosylcysteine amide (KYC), a novel, specific and non-toxic inhibitor of MPO. Behavioral testing, ischemic damage, blood-brain-barrier disruption, apoptosis, neutrophils infiltration, microglia/macrophage activation, and MPO oxidation were analyzed within a 7-day period after MCAO. Our studies show that KYC treatment significantly reduces neurological severity scores, infarct size, IgG extravasation, neutrophil infiltration, loss of neurons, apoptosis, and microglia/macrophage activation in the brains of MCAO mice. Immunofluorescence studies show that KYC treatment reduces the formation of chlorotyrosine (ClTyr), a fingerprint biomarker of MPO oxidation, nitrotyrosine (NO2Tyr), and 4-hydroxynonenal (4HNE) in MCAO mice. All oxidative products colocalized with MPO in the infarcted brains, suggesting that MPO-generated oxidants are involved in forming the oxidative products. MPO-generated oxidants play detrimental roles in causing brain damage after stroke which is effectively reduced by KYC.

  6. Quercitrin protects skin from UVB-induced oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

    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. - 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.

  7. Quercitrin protects skin from UVB-induced oxidative damage

    International Nuclear Information System (INIS)

    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

    2013-01-01

    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. - 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

  8. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles

    DEFF Research Database (Denmark)

    Møller, Peter; Danielsen, Pernille Høgh; Karottki, Dorina Gabriela

    2014-01-01

    at different locations (spatial variability), times (temporal variability) or particle size fraction across different experimental systems of acellular conditions, cultured cells, animals and humans. Nevertheless, there is substantial variation in the genotoxic, inflammation and oxidative stress potential......Generation of oxidatively damaged DNA by particulate matter (PM) is hypothesized to occur via production of reactive oxygen species (ROS) and inflammation. We investigated this hypothesis by comparing ROS production, inflammation and oxidatively damaged DNA in different experimental systems...... investigating air pollution particles. There is substantial evidence indicating that exposure to air pollution particles was associated with elevated levels of oxidatively damaged nucleobases in circulating blood cells and urine from humans, which is supported by observations of elevated levels of genotoxicity...

  9. Stable markers of oxidant damage to proteins and their application in the study of human disease

    DEFF Research Database (Denmark)

    Davies, Michael Jonathan; Fu, S; Wang, H

    1999-01-01

    The mechanisms of formation and the nature of the altered amino acid side chains formed on proteins subjected to oxidant attack are reviewed. The use of stable products of protein side chain oxidation as potential markers for assessing oxidative damage in vivo in humans is discussed. The methods...... developed in the authors laboratories are outlined, and the advantages and disadvantages of these techniques compared with other methodologies for assessing oxidative damage to proteins and other macromolecules. Evidence is presented to show that protein oxidation products are sensitive markers of oxidative...... damage, that the pattern of products detected may yield information as to the nature of the original oxidative insult, and that the levels of oxidized side-chains can, in certain circumstances, be much higher than those of other markers of oxidation such as lipid hydroperoxides....

  10. Inflammation, oxidative DNA damage, and carcinogenesis

    International Nuclear Information System (INIS)

    Lewis, J.G.; Adams, D.O.

    1987-01-01

    Inflammation has long been associated with carcinogenesis, especially in the promotion phase. The mechanism of action of the potent inflammatory agent and skin promoter 12-tetradecanoyl phorbol-13-acetate (TPA) is unknown. It is though that TPA selectively enhances the growth of initiated cells, and during this process, initiated cells progress to the preneoplastic state and eventually to the malignant phenotype. The authors and others have proposed that TPA may work, in part, by inciting inflammation and stimulating inflammatory cells to release powerful oxidants which then induce DNA damage in epidermal cells. Macrophages cocultured with target cells and TPA induce oxidized thymine bases in the target cells. This process is inhibited by both catalase and inhibitors of lipoxygenases, suggesting the involvement of both H 2 O 2 and oxidized lipid products. In vivo studies demonstrated that SENCAR mice, which are sensitive to promotion by TPA, have a more intense inflammatory reaction in skin that C57LB/6 mice, which are resistant to promotion by TPA. In addition, macrophages from SENCAR mice release more H 2 O 2 and metabolites of AA, and induce more oxidative DNA damage in cocultured cells than macrophages from C57LB/6 mice. These data support the hypothesis that inflammation and the release of genotoxic oxidants may be one mechanism whereby initiated cells receive further genetic insults. They also further complicate risk assessment by suggesting that some environmental agents may work indirectly by subverting host systems to induce damage rather than maintaining homeostasis

  11. Copper-mediated oxidative degradation of catecholamines and oxidative damage of protein

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, P.R.; Harria, M.I.N.; Felix, J.M.; Hoffmann, M.E. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia

    1997-12-31

    Full text. Degradative oxidation of catecholamines has been a matter of large interest in recent years due to the evidences associating their autoxidation with the etiology of neurotoxic and cardiotoxic processes. In this work we present data on the degradative oxidation of catecholamines of physiological importance: isoproterenol (IP), epinephrine (EP), norepinephrine (NEP), deoxyepinephrine (DEP) and dopamine (DA). The degradative oxidation of the catecholamines was followed by measurement of spectral changes and oxygen consumption by neutral aqueous solutions. The data show that Cu{sup 2+} strongly accelerated the rate of catecholamine oxidation, following the decreasing order; EP>DEP>IP>NEP>DA. The production of superoxide anion radical during catecholamine oxidation was very slow, even in the presence of Cu{sup 2+}. The ability of IP to induce damages on bovine serum albumin (BSA) was determined by measuring the formation of carbonyl-groups in the protein, detected by reduction with tritiated Na BH{sub 4}. The incubation of BSA with IP (50-500{mu}M), in the presence of 100{mu}M Cu{sup 2+} leaded to an increased and dose dependent {sup 3} H-incorporation by the oxidized protein. The production of oxidative damage by IP/Cu{sup 2+} was accompanied by marked BSA fragmentation, detected by SDS-polyacrylamide gel dependent (25-400{mu}M IP) des appearance of the original BSA band and appearance of smaller fragments spread in the gel, when incubation has been done in the presence of 100{mu}M Cu{sup 2+}. These results suggest that copper-catalysed oxidative degradation of proteins induced by catecholamines might be critically involved in the toxic action of these molecules

  12. Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

    Directory of Open Access Journals (Sweden)

    José A. Hernández

    2016-01-01

    Full Text Available 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.

  13. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha.

    Science.gov (United States)

    Wu, Shan; Ren, Jun

    2006-02-13

    Diabetes mellitus leads to thiamine deficiency and multiple organ damage including diabetic neuropathy. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cerebral oxidative stress. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg, i.p.). Fourteen days later, control and diabetic (fasting blood glucose >13.9 mM) mice received benfotiamine (100 mg/kg/day, i.p.) for 14 days. Oxidative stress and protein damage were evaluated by glutathione/glutathione disulfide (GSH/GSSG) assay and protein carbonyl formation, respectively. Pro-oxidative or pro-inflammatory factors including advanced glycation end-product (AGE), tissue factor and tumor necrosis factor-alpha (TNF-alpha) were evaluated by immunoblot analysis. Four weeks STZ treatment led to hyperglycemia, enhanced cerebral oxidative stress (reduced GSH/GSSG ratio), elevated TNF-alpha and AGE levels without changes in protein carbonyl or tissue factor. Benfotiamine alleviated diabetes-induced cerebral oxidative stress without affecting levels of AGE, protein carbonyl, tissue factor and TNF-alpha. Collectively, our results indicated benfotiamine may antagonize diabetes-induced cerebral oxidative stress through a mechanism unrelated to AGE, tissue factor and TNF-alpha.

  14. Effects of Mountain Ultra-Marathon Running on ROS Production and Oxidative Damage by Micro-Invasive Analytic Techniques.

    Directory of Open Access Journals (Sweden)

    Simona Mrakic-Sposta

    Full Text Available Aiming to gain a detailed insight into the physiological mechanisms involved under extreme conditions, a group of experienced ultra-marathon runners, performing the mountain Tor des Géants® ultra-marathon: 330 km trail-run in Valle d'Aosta, 24000 m of positive and negative elevation changes, was monitored. ROS production rate, antioxidant capacity, oxidative damage and inflammation markers were assessed, adopting micro-invasive analytic techniques.Forty-six male athletes (45.04±8.75 yr, 72.6±8.4 kg, 1.76±0.05 m were tested. Capillary blood and urine were collected before (Pre-, in the middle (Middle- and immediately after (Post- Race. Samples were analyzed for: Reactive Oxygen Species (ROS production by Electron Paramagnetic Resonance; Antioxidant Capacity by Electrochemistry; oxidative damage (8-hydroxy-2-deoxy Guanosine: 8-OH-dG; 8-isoprostane: 8-isoPGF2α and nitric oxide metabolites by enzymatic assays; inflammatory biomarkers (plasma and urine interleukin-6: IL-6-P and IL-6-U by enzyme-linked immunosorbent assays (ELISA; Creatinine and Neopterin by HPLC, hematologic (lactate, glucose and hematocrit and urine parameters by standard analyses.Twenty-five athletes finished the race, while twenty-one dropped out of it. A significant increase (Post-Race vs Pre of the ROS production rate (2.20±0.27 vs 1.65±0.22 μmol.min-1, oxidative damage biomarkers (8-OH-dG: 6.32±2.38 vs 4.16±1.25 ng.mg-1 Creatinine and 8-isoPGF2α: 1404.0±518.30 vs 822.51±448.91 pg.mg-1Creatinine, inflammatory state (IL-6-P: 66.42±36.92 vs 1.29±0.54 pg.mL-1 and IL-6-U: 1.33±0.56 vs 0.71±0.17 pg.mL1 and lactate production (+190%, associated with a decrease of both antioxidant capacity (-7% and renal function (i.e. Creatinine level +76% was found.The used micro-invasive analytic methods allowed us to perform most of them before, during and immediately after the race directly in the field, by passing the need of storing and transporting samples for further analysis

  15. Endogenous melatonin and oxidatively damaged guanine in DNA

    DEFF Research Database (Denmark)

    Davanipour, Zoreh; Poulsen, Henrik E; Weimann, Allan

    2009-01-01

    overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were...... attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. METHODS: Mother...

  16. Endogenous melatonin and oxidatively damaged guanine in DNA

    Directory of Open Access Journals (Sweden)

    Poulsen Henrik E

    2009-10-01

    Full Text Available Abstract Background A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. Methods Mother-father-daughter(s families (n = 55 were recruited and provided complete overnight urine samples. Total overnight creatinine-adjusted 6-sulphatoxymelatonin (aMT6s/Cr has been shown to be highly correlated with total overnight melatonin production. Urinary 8-oxo-7,8-dihydro-guanine (8-oxoGua results from the repair of DNA or RNA guanine via the nucleobase excision repair pathway, while urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG may possibly result from the repair of DNA guanine via the nucleotide excision repair pathway. Total overnight urinary levels of 8-oxodG and 8-oxoGua are therefore a measure of total overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were calculated for aMT6s/Cr, 8-oxodG, and 8-oxoGua. Regression analyses of 8-oxodG and 8-oxoGua on aMT6s/Cr were conducted for mothers, fathers, and daughters separately, adjusting for age and BMI (or weight. Results Among the mothers, age range 42-80, lower melatonin production (as measured by aMT6s/CR was associated with significantly higher levels of 8-oxodG (p Conclusion Low levels of endogenous melatonin production among older individuals may lead to

  17. Oxidative DNA damage & repair: An introduction.

    Science.gov (United States)

    Cadet, Jean; Davies, Kelvin J A

    2017-06-01

    This introductory article should be viewed as a prologue to the Free Radical Biology & Medicine Special Issue devoted to the important topic of Oxidatively Damaged DNA and its Repair. This special issue is dedicated to Professor Tomas Lindahl, co-winner of the 2015 Nobel Prize in Chemistry for his seminal discoveries in the area repair of oxidatively damaged DNA. In the past several years it has become abundantly clear that DNA oxidation is a major consequence of life in an oxygen-rich environment. Concomitantly, survival in the presence of oxygen, with the constant threat of deleterious DNA mutations and deletions, has largely been made possible through the evolution of a vast array of DNA repair enzymes. The articles in this Oxidatively Damaged DNA & Repair special issue detail the reactions by which intracellular DNA is oxidatively damaged, and the enzymatic reactions and pathways by which living organisms survive such assaults by repair processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Oxidative DNA damage and oxidative stress in lead-exposed workers.

    Science.gov (United States)

    Dobrakowski, M; Pawlas, N; Kasperczyk, A; Kozłowska, A; Olewińska, E; Machoń-Grecka, A; Kasperczyk, S

    2017-07-01

    There are many discrepancies among the results of studies on the genotoxicity of lead. The aim of the study was to explore lead-induced DNA damage, including oxidative damage, in relation to oxidative stress intensity parameters and the antioxidant defense system in human leukocytes. The study population consisted of 100 male workers exposed to lead. According to the blood lead (PbB) levels, they were divided into the following three subgroups: a group with PbB of 20-35 μg/dL (low exposure to lead (LE) group), a group with a PbB of 35-50 µg/dL (medium exposure to lead (ME) group), and a group with a PbB of >50 μg/dL (high exposure to lead (HE) group). The control group consisted of 42 healthy males environmentally exposed to lead (PbB lead exposure induces DNA damage, including oxidative damage, in human leukocytes. The increase in DNA damage was accompanied by an elevated intensity of oxidative stress.

  19. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, Gary M. [Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW (Australia)]. E-mail: garyh@med.usyd.edu.au

    2005-04-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

  20. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    International Nuclear Information System (INIS)

    Halliday, Gary M.

    2005-01-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans

  1. Oxidative DNA damage during sleep periods among nightshift workers.

    Science.gov (United States)

    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/

  2. Damage of polyesters by the atmospheric free radical oxidant NO3 •: a product study involving model systems

    Science.gov (United States)

    Goeschen, Catrin

    2013-01-01

    Summary Manufactured polymer materials are used in increasingly demanding applications, but their lifetime is strongly influenced by environmental conditions. In particular, weathering and ageing leads to dramatic changes in the properties of the polymers, which results in decreased service life and limited usage. Despite the heavy reliance of our society on polymers, the mechanism of their degradation upon exposure to environmental oxidants is barely understood. In this work, model systems of important structural motifs in commercial high-performing polyesters were used to study the reaction with the night-time free radical oxidant NO3 • in the absence and presence of other radical and non-radical oxidants. Identification of the products revealed ‘hot spots’ in polyesters that are particularly vulnerable to attack by NO3 • and insight into the mechanism of oxidative damage by this environmentally important radical. It is suggested that both intermediates as well as products of these reactions are potentially capable of promoting further degradation processes in polyesters under environmental conditions. PMID:24204400

  3. Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae.

    Science.gov (United States)

    Doudican, Nicole A; Song, Binwei; Shadel, Gerald S; Doetsch, Paul W

    2005-06-01

    Mitochondria contain their own genome, the integrity of which is required for normal cellular energy metabolism. Reactive oxygen species (ROS) produced by normal mitochondrial respiration can damage cellular macromolecules, including mitochondrial DNA (mtDNA), and have been implicated in degenerative diseases, cancer, and aging. We developed strategies to elevate mitochondrial oxidative stress by exposure to antimycin and H(2)O(2) or utilizing mutants lacking mitochondrial superoxide dismutase (sod2Delta). Experiments were conducted with strains compromised in mitochondrial base excision repair (ntg1Delta) and oxidative damage resistance (pif1Delta) in order to delineate the relationship between these pathways. We observed enhanced ROS production, resulting in a direct increase in oxidative mtDNA damage and mutagenesis. Repair-deficient mutants exposed to oxidative stress conditions exhibited profound genomic instability. Elimination of Ntg1p and Pif1p resulted in a synergistic corruption of respiratory competency upon exposure to antimycin and H(2)O(2). Mitochondrial genomic integrity was substantially compromised in ntg1Delta pif1Delta sod2Delta strains, since these cells exhibit a total loss of mtDNA. A stable respiration-defective strain, possessing a normal complement of mtDNA damage resistance pathways, exhibited a complete loss of mtDNA upon exposure to antimycin and H(2)O(2). This loss was preventable by Sod2p overexpression. These results provide direct evidence that oxidative mtDNA damage can be a major contributor to mitochondrial genomic instability and demonstrate cooperation of Ntg1p and Pif1p to resist the introduction of lesions into the mitochondrial genome.

  4. Ultrasensitive determination of DNA oxidation products by gas chromatography-tandem mass spectrometry and the role of antioxidants in the prevention of oxidative damage.

    Science.gov (United States)

    Dawbaa, Sam; Aybastıer, Önder; Demir, Cevdet

    2017-04-15

    Oxidative stress is considered as one of the significant causes of DNA damage which in turn contributes to cell death through a series of intermediate processes such as cancer formation, mutation, and aging. Natural sources such as plant and fruit products have provided us with interesting substances of antioxidant activity that could be recruited in protecting the genetic materials of the cells. This study is an effort to discover some of those antioxidants effects in their standard and natural forms by performing an ultrasensitive determination of the products of DNA oxidation using GC-MS/MS. Experiments were used to determine the direct antioxidant activity of the substances contained in the tendrils of Vitis vinifera (var. alphonse) by extracting them and achieving Folin-Ciocalteau and CHROMAC analyses to determine the total phenolic content (TPC) and the antioxidant capacity of the extract, respectively; results revealed a phenolic content of 11.39±0.30mg Gallic Acid Equivalent (GAE)/g of the plant's fresh weight (FW) by Folin-Ciocalteau and 8.17±0.49mg Trolox Equivalent (TE)/g FW by CHROMAC assays. The qualitative analysis of the plant extract by HPLC-DAD technique revealed that two flavonoid glycosides namely rutin and isoquercitrin in addition to chlorogenic acid were contained in the extract. The determination of the DNA oxidation products was performed after putting DNA, rutin and isoquercitrin standard samples with different concentration, and the extract's sample under oxidative stress. Eighteen DNA oxidation products were traced using GC-MS/MS with ultra-sensitivity and the experiments proved a significant decrease in the concentration of the DNA oxidation products when the extract was used as a protectant against the oxidative stress. It is believed by conclusion that the extract of V. vinifera's (var. alphonse) tendrils has a good antioxidant activity; hence it is recommended to be used as a part of the daily healthy food list if possible

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

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2013-04-15

    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 not 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

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

    International Nuclear Information System (INIS)

    Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

    2013-01-01

    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 not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ 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

  7. Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts.

    Directory of Open Access Journals (Sweden)

    Natalie R Gassman

    Full Text Available Bisphenol A (BPA is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3 or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    Laha, Dipranjan; Pramanik, Arindam; Laskar, Aparna; Jana, Madhurya; Pramanik, Panchanan; Karmakar, Parimal

    2014-01-01

    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. Spherical 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Laha, Dipranjan; Pramanik, Arindam [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Laskar, Aparna [CSIR-Indian Institute of Chemical Biology, Kolkata 700032 (India); Jana, Madhurya [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Pramanik, Panchanan [Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India); Karmakar, Parimal, E-mail: pkarmakar_28@yahoo.co.in [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India)

    2014-11-15

    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. Spherical 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.

  11. Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution

    DEFF Research Database (Denmark)

    Møller, Peter; Loft, Steffen

    2010-01-01

    BACKGROUND: Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids. OBJECTIVE: We determined whether levels of oxidatively damaged DNA and lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers...... of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes. DATA SOURCES: We identified publications that reported estimated associations between environmental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also...... identified publications from reference lists and articles cited in the Web of Science. DATA EXTRACTION: For each study, we obtained information on the estimated effect size to calculate the standardized mean difference (unitless) and determined the potential for errors in exposure assessment and analysis...

  12. Transgenic Mouse Model for Reducing Oxidative Damage in Bone

    Science.gov (United States)

    Schreurs, Ann-Sofie; Torres, S.; Truong, T.; Moyer, E. L.; Kumar, A.; Tahimic, Candice C. G.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

    2016-01-01

    Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the

  13. Aging and oxidatively damaged nuclear DNA in animal organs

    DEFF Research Database (Denmark)

    Møller, Peter; Løhr, Mille; Folkmann, Janne K

    2010-01-01

    Oxidative stress is considered to contribute to aging and is associated with the generation of oxidatively damaged DNA, including 8-oxo-7,8-dihydroguanine. We have identified 69 studies that have measured the level of oxidatively damaged DNA in organs of animals at various ages. In general, organs...... with limited cell proliferation, i.e., liver, kidney, brain, heart, pancreas, and muscle, tended to show accumulation of DNA damage with age, whereas organs with highly proliferating cells, such as intestine, spleen, and testis, showed more equivocal or no effect of age. A restricted analysis of studies...... evidence for aging-associated accumulation of oxidatively damaged DNA in organs with limited cell proliferation....

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

    Science.gov (United States)

    Foyer, Christine H; Ruban, Alexander V; Noctor, Graham

    2017-03-07

    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. © 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY).

  15. Ionizing radiation, antioxidant response and oxidative damage: A meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Einor, D., E-mail: daniel@einor.com [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); Bonisoli-Alquati, A., E-mail: andreabonisoli@gmail.com [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); School of Renewable Natural Resources, Louisiana State University AgCenter, Baton Rouge, LA 70803 (United States); Costantini, D., E-mail: davidcostantini@libero.it [Department of Biology, University of Antwerp, Wilrijk, B-2610, Antwerp (Belgium); Mousseau, T.A., E-mail: mousseau@sc.edu [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); Faculty of Bioscience and Biotechnology, Chubu University, Kasugai (Japan); Møller, A.P., E-mail: anders.moller@u-psud.fr [Laboratoire d' Ecologie, Systématique et Evolution, CNRS UMR 8079, Université Paris-Sud, Bâtiment 362, F-91405 Orsay Cedex (France)

    2016-04-01

    One mechanism proposed as a link between exposure to ionizing radiation and detrimental effects on organisms is oxidative damage. To test this hypothesis, we surveyed the scientific literature on the effects of chronic low-dose ionizing radiation (LDIR) on antioxidant responses and oxidative damage. We found 40 publications and 212 effect sizes for antioxidant responses and 288 effect sizes for effects of oxidative damage. We performed a meta-analysis of signed and unsigned effect sizes. We found large unsigned effects for both categories (0.918 for oxidative damage; 0.973 for antioxidant response). Mean signed effect size weighted by sample size was 0.276 for oxidative damage and − 0.350 for antioxidant defenses, with significant heterogeneity among effects for both categories, implying that ionizing radiation caused small to intermediate increases in oxidative damage and small to intermediate decreases in antioxidant defenses. Our estimates are robust, as shown by very high fail-safe numbers. Species, biological matrix (tissue, blood, sperm) and age predicted the magnitude of effects for oxidative damage as well as antioxidant response. Meta-regression models showed that effect sizes for oxidative damage varied among species and age classes, while effect sizes for antioxidant responses varied among species and biological matrices. Our results are consistent with the description of mechanisms underlying pathological effects of chronic exposure to LDIR. Our results also highlight the importance of resistance to oxidative stress as one possible mechanism associated with variation in species responses to LDIR-contaminated areas. - Highlights: • There is interest in variation in metabolic effects of chronic low-dose ionizing radiation • A random effect meta-analysis of effect sizes of radioactive contamination was performed • We found significant effects of radiation on oxidative damage and antioxidant response • We found significant heterogeneity among

  16. Ionizing radiation, antioxidant response and oxidative damage: A meta-analysis.

    Science.gov (United States)

    Einor, D; Bonisoli-Alquati, A; Costantini, D; Mousseau, T A; Møller, A P

    2016-04-01

    One mechanism proposed as a link between exposure to ionizing radiation and detrimental effects on organisms is oxidative damage. To test this hypothesis, we surveyed the scientific literature on the effects of chronic low-dose ionizing radiation (LDIR) on antioxidant responses and oxidative damage. We found 40 publications and 212 effect sizes for antioxidant responses and 288 effect sizes for effects of oxidative damage. We performed a meta-analysis of signed and unsigned effect sizes. We found large unsigned effects for both categories (0.918 for oxidative damage; 0.973 for antioxidant response). Mean signed effect size weighted by sample size was 0.276 for oxidative damage and -0.350 for antioxidant defenses, with significant heterogeneity among effects for both categories, implying that ionizing radiation caused small to intermediate increases in oxidative damage and small to intermediate decreases in antioxidant defenses. Our estimates are robust, as shown by very high fail-safe numbers. Species, biological matrix (tissue, blood, sperm) and age predicted the magnitude of effects for oxidative damage as well as antioxidant response. Meta-regression models showed that effect sizes for oxidative damage varied among species and age classes, while effect sizes for antioxidant responses varied among species and biological matrices. Our results are consistent with the description of mechanisms underlying pathological effects of chronic exposure to LDIR. Our results also highlight the importance of resistance to oxidative stress as one possible mechanism associated with variation in species responses to LDIR-contaminated areas. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Oxidative damage and cell-programmed death induced in Zea mays L. by allelochemical stress.

    Science.gov (United States)

    Ciniglia, Claudia; Mastrobuoni, Francesco; Scortichini, Marco; Petriccione, Milena

    2015-05-01

    The allelochemical stress on Zea mays was analyzed by using walnut husk washing waters (WHWW), a by-product of Juglans regia post-harvest process, which possesses strong allelopathic potential and phytotoxic effects. Oxidative damage and cell-programmed death were induced by WHWW in roots of maize seedlings. Treatment induced ROS burst, with excess of H2O2 content. Enzymatic activities of catalase were strongly increased during the first hours of exposure. The excess in malonildialdehyde following exposure to WHWW confirmed that oxidative stress severely damaged maize roots. Membrane alteration caused a decrease in NADPH oxidase activity along with DNA damage as confirmed by DNA laddering. The DNA instability was also assessed through sequence-related amplified polymorphism assay, thus suggesting the danger of walnut processing by-product and focusing the attention on the necessity of an efficient treatment of WHWW.

  18. Alkali production associated with malolactic fermentation by oral streptococci and protection against acid, oxidative, or starvation damage.

    Science.gov (United States)

    Sheng, Jiangyun; Baldeck, Jeremiah D; Nguyen, Phuong T M; Quivey, Robert G; Marquis, Robert E

    2010-07-01

    Alkali production by oral streptococci is considered important for dental plaque ecology and caries moderation. Recently, malolactic fermentation (MLF) was identified as a major system for alkali production by oral streptococci, including Streptococcus mutans. Our major objectives in the work described in this paper were to further define the physiology and genetics of MLF of oral streptococci and its roles in protection against metabolic stress damage. L-Malic acid was rapidly fermented to L-lactic acid and CO(2) by induced cells of wild-type S. mutans, but not by deletion mutants for mleS (malolactic enzyme) or mleP (malate permease). Mutants for mleR (the contiguous regulator gene) had intermediate capacities for MLF. Loss of capacity to catalyze MLF resulted in loss of capacity for protection against lethal acidification. MLF was also found to be protective against oxidative and starvation damage. The capacity of S. mutans to produce alkali from malate was greater than its capacity to produce acid from glycolysis at low pH values of 4 or 5. MLF acted additively with the arginine deiminase system for alkali production by Streptococcus sanguinis, but not with urease of Streptococcus salivarius. Malolactic fermentation is clearly a major process for alkali generation by oral streptococci and for protection against environmental stresses.

  19. Alkali production associated with malolactic fermentation by oral streptococci and protection against acid, oxidative, or starvation damage

    Science.gov (United States)

    Sheng, Jiangyun; Baldeck, Jeremiah D.; Nguyen, Phuong T.M.; Quivey, Robert G.; Marquis, Robert E.

    2011-01-01

    Alkali production by oral streptococci is considered important for dental plaque ecology and caries moderation. Recently, malolactic fermentation (MLF) was identified as a major system for alkali production by oral streptococci, including Streptococcus mutans. Our major objectives in the work described in this paper were to further define the physiology and genetics of MLF of oral streptococci and its roles in protection against metabolic stress damage. l-Malic acid was rapidly fermented to l-lactic acid and CO2 by induced cells of wild-type S. mutans, but not by deletion mutants for mleS (malolactic enzyme) or mleP (malate permease). Mutants for mleR (the contiguous regulator gene) had intermediate capacities for MLF. Loss of capacity to catalyze MLF resulted in loss of capacity for protection against lethal acidification. MLF was also found to be protective against oxidative and starvation damage. The capacity of S. mutans to produce alkali from malate was greater than its capacity to produce acid from glycolysis at low pH values of 4 or 5. MLF acted additively with the arginine deiminase system for alkali production by Streptococcus sanguinis, but not with urease of Streptococcus salivarius. Malolactic fermentation is clearly a major process for alkali generation by oral streptococci and for protection against environmental stresses. PMID:20651853

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

    Science.gov (United States)

    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.

  1. Guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health (Revision 1)

    DEFF Research Database (Denmark)

    Sjödin, Anders Mikael

    2018-01-01

    of additional health claim applications related to antioxidants, oxidative damage and cardiovascular health, and the information collected from a Grant launched in 2014. This guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to the antioxidants......EFSA asked the Panel on Dietetic Products, Nutrition and Allergies (NDA) to update the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. The update takes into accounts experiences gained with evaluation......, oxidative damage and cardiovascular health. The document was subject to public consultation (from 12 July to 3 September 2017). This document supersedes the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011...

  2. Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals

    DEFF Research Database (Denmark)

    Møller, Peter; Jensen, Ditte Marie; Christophersen, Daniel Vest

    2015-01-01

    -reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations...... of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2 , carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration-dependent associations between ENM exposure...... and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential. Environ. Mol. Mutagen., 2014. © 2014 Wiley Periodicals, Inc....

  3. Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

    DEFF Research Database (Denmark)

    Jantzen, Kim; Roursgaard, Martin; Madsen, Claus Desler

    2012-01-01

    Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung...... treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine...... relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells....

  4. Application of lipid peroxidation and protein oxidation biomarkers for oxidative damage in mammalian cells. A comparison with two fluorescent probes

    NARCIS (Netherlands)

    Orhan, H.; Gurer-Orhan, H.; Vriese, E.; Vermeulen, N.P.E.; Meerman, J.H.N.

    2006-01-01

    We recently developed two biomarker sets for oxidative damage: one for determination of lipid peroxidation (LPO) degradation products; acetaldehyde, propanal, butanal, pentanal, hexanal, heptanal, octanal, nonanal, malondialdehyde and acetone, by a gas chromatography-electron capture detection

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

    Science.gov (United States)

    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.

  6. Behavior of fission products released from severely damaged fuel during the PBF severe fuel damage tests

    International Nuclear Information System (INIS)

    Osetek, D.J.; Cronenberg, A.W.; Hagrman, D.L.; Broughton, J.M.; Rest, J.

    1984-01-01

    The results of fission product release behavior during the first two Power Burst Facility Severe Fuel Damage tests are presented. Measured fission product release is compared with calculated release using temperature dependent release rate correlations and FASTGRASS analysis. The test results indicate that release from fuel of the high volatility fission products (Xe, Kr, I, Cs, and Te) is strongly influenced by parameters other than fuel temperature; namely fuel/fission product morphology, fuel and cladding oxidation state, extent of fuel liquefaction, and quench induced fuel shattering. Fission product transport from the test fuel through the sample system was strongly influenced by chemical effects. Holdup of I and Cs was affected by fission product chemistry, and transport time while Te release was primarily influenced by the extent of zircaloy oxidation. Analysis demonstrates that such integral test data can be used to confirm physical, chemical, and mechanistic models of fission product behavior for severe accident conditions

  7. Protection of naturally occurring antioxidants against oxidative damages to protein

    International Nuclear Information System (INIS)

    Zhu Hongping; Zhang Zhaoxia; Hao Shumei; Wang Wenfeng; Yao Side

    2006-01-01

    One of the most compelling theories explaining age-related deterioration is the free radical theory of aging. It has been shown that reactive oxygen species are involved in oxidative damages to biomolecules and this is related to a number of diseases. Proteins, the second most abundant components of cells (next to water by weight), are now increasingly recognized as major biological targets of oxidative damages. Convincing evidences have indicated that damages to protein have been implicated in Alzheimer's disease, Parkinson's disease, cancer, and aging. Antioxidant has been the subject of great attention because they are known to lower the risk of cardiovascular and other diseases. Hydroxycinnamic acid derivatives (HCAs) are antioxidants abundant in tea, red wine, fruits, beverages and various medicinal plants. Results showed that they exhibit remarkable activity for scavenging oxidizing radicals and triplet states. The protective effects of four kinds of HCAs on oxidative damages to lysozyme were investigated in our lab. Protein damages induced by two different paradigms: riboflavin-sensitized photooxidation and hydroxyl ( . OH)-mediated oxidation, were investigated using polyacrylamide gel electrophoresis. HCAs were found to inhibit the cross-linking of protein induced by riboflavin-mediated photooxidation. HCAs also exhibited protection effect on lysozyme damage induced by γ-ray irradiation. The rate constants for quenching triplet state of riboflavin by lysozyme and HCAs were obtained using laser flash photolysis. The protective mechanism was proposed based on the dynamic study. HCAs were found to protect protein against oxidation by scavenging oxidizing species and repairing the damaged protein. (authors)

  8. Oxidative Damage Caused by Common Foodborne Pathogenic Bacteria in Egg Yolk

    Directory of Open Access Journals (Sweden)

    Reyhaneh Afshordi

    2016-02-01

    Full Text Available Background: Bacteria in foodstuff are the most important agent of foodborne disease. Aside from their infectious effects, obligate aerobes have a respiratory metabolism with oxygen as the terminal electron acceptor. Therefore, they can produce reactive oxygen species and free radicals in contaminated food. Malondialdehyde (MDA is a product of lipid peroxidation used as an indicator of oxidative stress. Objectives: This study aimed to evaluate the oxidative damage produced by two common food pathogenic bacteria in foodstuff. Materials and Methods: The egg yolks were incubated with different dilutions (105,106, and 107 of Staphylococcus aureus and Salmonella enteritidis at 37°C for 20 hours. The level of MDA in egg yolk was measured by fast and simple enzymatic or colorimetric methods, such as the thiobarbituric acid reactive species method. Results: The high group (107 had a higher MDA level of 1.97 ± 0.11 (μg MDA/g in S. aureus and 1.65 ± 0.27 (mg MDA/L in S. enteritidis than the control (0.90 ± 0.13 mg MDA/L. Conclusions: We concluded that common food pathogenic bacteria can induce oxidative damage in foodstuff aside from other common problems. Heating or sterilization methods cannot protect foodstuff from the damage caused by the presence of pathogenic bacteria.

  9. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.

    Science.gov (United States)

    Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E M

    2017-04-29

    Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3 H )-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32 P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe₃O₄-NPs. Significant dose-response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

  10. Hawkmoths use nectar sugar to reduce oxidative damage from flight.

    Science.gov (United States)

    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.

  11. OXIDATIVE STRESS AND VASCULAR DAMAGE IN HYPOXIA PROCESSES. MALONDIALDEHYDE (MDA AS BIOMARKER FOR OXIDATIVE DAMAGE

    Directory of Open Access Journals (Sweden)

    Muñiz P

    2014-05-01

    Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.

  12. Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

    Energy Technology Data Exchange (ETDEWEB)

    Giovannelli, Lisa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)]. E-mail: lisag@pharm.unifi.it; Bellandi, Serena [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Pitozzi, Vanessa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Fabbri, Paolo [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Dolara, Piero [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Moretti, Silvia [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)

    2004-11-22

    Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

  13. Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

    International Nuclear Information System (INIS)

    Giovannelli, Lisa; Bellandi, Serena; Pitozzi, Vanessa; Fabbri, Paolo; Dolara, Piero; Moretti, Silvia

    2004-01-01

    Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo

  14. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2011-01-01

    Full Text Available Reactive oxygen species (ROS, including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

  15. Chemical Characterization and Reactivity of Fuel-Oxidizer Reaction Product

    Science.gov (United States)

    David, Dennis D.; Dee, Louis A.; Beeson, Harold D.

    1997-01-01

    Fuel-oxidizer reaction product (FORP), the product of incomplete reaction of monomethylhydrazine and nitrogen tetroxide propellants prepared under laboratory conditions and from firings of Shuttle Reaction Control System thrusters, has been characterized by chemical and thermal analysis. The composition of FORP is variable but falls within a limited range of compositions that depend on three factors: the fuel-oxidizer ratio at the time of formation; whether the composition of the post-formation atmosphere is reducing or oxidizing; and the reaction or post-reaction temperature. A typical composition contains methylhydrazinium nitrate, ammonium nitrate, methylammonium nitrate, and trace amounts of hydrazinium nitrate and 1,1-dimethylhydrazinium nitrate. Thermal decomposition reactions of the FORP compositions used in this study were unremarkable. Neither the various compositions of FORP, the pure major components of FORP, nor mixtures of FORP with propellant system corrosion products showed any unusual thermal activity when decomposed under laboratory conditions. Off-limit thruster operations were simulated by rapid mixing of liquid monomethylhydrazine and liquid nitrogen tetroxide in a confined space. These tests demonstrated that monomethylhydrazine, methylhydrazinium nitrate, ammonium nitrate, or Inconel corrosion products can induce a mixture of monomethylhydrazine and nitrogen tetroxide to produce component-damaging energies. Damaging events required FORP or metal salts to be present at the initial mixing of monomethylhydrazine and nitrogen tetroxide.

  16. Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

    Directory of Open Access Journals (Sweden)

    Viktor M Pastukh

    2011-03-01

    Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

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

    Science.gov (United States)

    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 (ptotal antioxidant capacity was significantly lower (ptotal antioxidant capacity and hemoglobin levels (r=0.706, ptotal 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.

  18. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Filippo Cellai

    2017-04-01

    Full Text Available Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosylpyrimido[1,2-α]purin-10(3H-one deoxyguanosine (M1dG and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe3O4-nanoparticles (NPs versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF of 186 kHz using 32P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe3O4-NPs. Significant dose–response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

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

    Science.gov (United States)

    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.

  20. The Inhibition Effect of Cell DNA Oxidative Damage and LDL Oxidation by Bovine Colostrums

    Directory of Open Access Journals (Sweden)

    Chih-Wei Chen

    2016-10-01

    Full Text Available In the present study, we investigated the effect of bovine colostrums on inhibition of DNA oxidative damage and low density lipoprotein (LDL oxidation in vitro. Results showed that whey and skimmed milk exhibited not only higher inhibitory activities of oxidative damage of deoxyribose but also an inhibitory effect on the breakdown of supercoiled DNA into open circular DNA and linear DNA. The quantities of 8-OH-2′-dG formed under whey, caseins and skimmed milk treatment were 0.24, 0.24 and 1.24 μg/mL, respectively. The quantity of malondialdehyde formed through LDL oxidation induced by copprous ion was significantly decreased as colostrums protein solutions were added, in which whey and caseins led to a more significant decrease than skimmed milk. The formation of conjugated dienes could be inhibited by treatment with colostrums protein solutions. Whey exhibited the longest lag time of conjugated dienes formation among the colostrums proteins. The lag time of the whey was 2.33 times that of the control. From the results of foregoing, the bovine colostrums protein has potential value in the inhibition of DNA oxidation damage and LDL oxidation.

  1. Repair of oxidative DNA damage by amino acids.

    Science.gov (United States)

    Milligan, J R; Aguilera, J A; Ly, A; Tran, N Q; Hoang, O; Ward, J F

    2003-11-01

    Guanyl radicals, the product of the removal of a single electron from guanine, are produced in DNA by the direct effect of ionizing radiation. We have produced guanyl radicals in DNA by using the single electron oxidizing agent (SCN)2-, itself derived from the indirect effect of ionizing radiation via thiocyanate scavenging of OH. We have examined the reactivity of guanyl radicals in plasmid DNA with the six most easily oxidized amino acids cysteine, cystine, histidine, methionine, tryptophan and tyrosine and also simple ester and amide derivatives of them. Cystine and histidine derivatives are unreactive. Cysteine, methionine, tyrosine and particularly tryptophan derivatives react to repair guanyl radicals in plasmid DNA with rate constants in the region of approximately 10(5), 10(5), 10(6) and 10(7) dm3 mol(-1) s(-1), respectively. The implication is that amino acid residues in DNA binding proteins such as histones might be able to repair by an electron transfer reaction the DNA damage produced by the direct effect of ionizing radiation or by other oxidative insults.

  2. Aging-associated oxidized albumin promotes cellular senescence and endothelial damage

    Directory of Open Access Journals (Sweden)

    Luna C

    2016-02-01

    Full Text Available Carlos Luna,1,* Matilde Alique,2,* Estefanía Navalmoral,2 Maria-Victoria Noci,3 Lourdes Bohorquez-Magro,2 Julia Carracedo,1 Rafael Ramírez2 1Nephrology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Reina Sofía University Hospital, Córdoba, Spain; 2Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Madrid, Spain; 3Anesthesia Unit, Reina sofía University Hospital, Córdoba, Spain*These authors contributed equally to this work Abstract: Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.Keywords: elderly, oxidative stress, microparticles, vascular damage

  3. Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage

    Directory of Open Access Journals (Sweden)

    Jiaxiang Shao

    2016-03-01

    Full Text Available Abstract SIRT6 is a NAD+-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.

  4. Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway

    Directory of Open Access Journals (Sweden)

    Peter Belenky

    2013-02-01

    Full Text Available Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.

  5. Oxidatively generated DNA/RNA damage in psychological stress states

    DEFF Research Database (Denmark)

    Jørgensen, Anders

    2013-01-01

    age-related somatic disorders. The overall aim of the PhD project was to investigate the relation between psychopathology, psychological stress, stress hormone secretion and oxidatively generated DNA and RNA damage, as measured by the urinary excretion of markers of whole-body DNA/RNA oxidation (8...... between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between psychological stress and oxidative stress on nucleic acids. Systemic oxidatively generated DNA/RNA damage was increased......Both non-pathological psychological stress states and mental disorders are associated with molecular, cellular and epidemiological signs of accelerated aging. Oxidative stress on nucleic acids is a critical component of cellular and organismal aging, and a suggested pathogenic mechanism in several...

  6. Oxidative damage of DNA in subjects occupationally exposed to lead.

    Science.gov (United States)

    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 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.

  7. Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress

    International Nuclear Information System (INIS)

    Pina-Guzman, B.; Solis-Heredia, M.J.; Rojas-Garcia, A.E.; Uriostegui-Acosta, M.; Quintanilla-Vega, B.

    2006-01-01

    Organophosphorous (OP) pesticides are considered genotoxic mainly to somatic cells, but results are not conclusive. Few studies have reported OP alterations on sperm chromatin and DNA, and oxidative stress has been related to their toxicity. Sperm cells are very sensitive to oxidative damage which has been associated with reproductive dysfunctions. We evaluated the effects of methyl-parathion (Me-Pa; a widely used OP) on sperm DNA, exploring the sensitive stage(s) of spermatogenesis and the relationship with oxidative stress. Male mice (10-12-weeks old) were administered Me-Pa (3-20 mg/kg bw/i.p.) and euthanized at 7- or 28-days post-treatment. Mature spermatozoa were obtained and evaluated for chromatin structure through SCSA (Sperm Chromatin Structure Assay; DNA Fragmentation Index parameters: Mean DFI and DFI%) and chromomycin-A 3 (CMA 3 )-staining, for DNA damage through in situ-nick translation (NT-positive) and for oxidative stress through lipid peroxidation (LPO; malondialdehyde production). At 7-days post-treatment (mature spermatozoa when Me-Pa exposure), dose-dependent alterations in chromatin structure (Mean DFI and CMA 3 -staining) were observed, as well as increased DNA damage, from 2-5-fold in DFI% and NT-positive cells. Chromatin alterations and DNA damage were also observed at 28-days post-treatment (cells at meiosis at the time of exposure); suggesting that the damage induced in spermatocytes was not repaired. Positive correlations were observed between LPO and sperm DNA-related parameters. These data suggest that oxidative stress is related to Me-Pa alterations on sperm DNA integrity and cells at meiosis (28-days post-treatment) and epididymal maturation (7-days post-treatment) are Me-Pa targets. These findings suggest a potential risk of Me-Pa to the offspring after transmission

  8. Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents

    Directory of Open Access Journals (Sweden)

    Raúl Enrique Cuevas-Durán

    2017-11-01

    Full Text Available Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co and Rosmarinus officinalis (Ro extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a sham; (b vehicle-treated myocardial infarction (MI (MI-V; (c Ro extract-treated myocardial infarction (MI-Ro; (d Co extract-treated myocardial infarction (MI-Co; or (e Ro+Co-treated myocardial infarction (MI-Ro+Co. Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2′-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1, increased vasodilators agents (angiotensin 1–7 and bradikinin and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.

  9. Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups.

    Science.gov (United States)

    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.

  10. SIRT3 mediates decrease of oxidative damage and prevention of ageing in porcine fetal fibroblasts.

    Science.gov (United States)

    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.

  11. Transport stress induces heart damage in newly hatched chicks via blocking the cytoprotective heat shock response and augmenting nitric oxide production.

    Science.gov (United States)

    Sun, F; Zuo, Y-Z; Ge, J; Xia, J; Li, X-N; Lin, J; Zhang, C; Xu, H-L; Li, J-L

    2018-04-20

    Transport stress affects the animal's metabolism and psychological state. As a pro-survival pathway, the heat shock response (HSR) protects healthy cells from stressors. However, it is unclear whether the HSR plays a role in transport stress-induced heart damage. To evaluate the effects of transport stress on heart damage and HSR protection, newly hatched chicks were treated with transport stress for 2 h, 4 h and 8 h. Transport stress caused decreases in body weight and increases in serum creatine kinase (CK) activity, nitric oxide (NO) content in heart tissue, cardiac nitric oxide syntheses (NOS) activity and NOS isoforms transcription. The mRNA expression of heat shock factors (HSFs, including HSF1-3) and heat shock proteins (HSPs, including HSP25, HSP40, HSP47, HSP60, HSP70, HSP90 and HSP110) in the heart of 2 h transport-treated chicks was upregulated. After 8 h of transport stress in chicks, the transcription levels of the same HSPs and HSF2 were reduced in the heart. It was also found that the changes in the HSP60, HSP70 and HSP90 protein levels had similar tendencies. These results suggested that transport stress augmented NO generation through enhancing the activity of NOS and the transcription of NOS isoforms. Therefore, this study provides new evidence that transport stress induces heart damage in the newly hatched chicks by blocking the cytoprotective HSR and augmenting NO production.

  12. Mitochondrial DNA damage and oxidative damage in HL-60 cells exposed to 900 MHz radiofrequency fields

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yulong; Zong, Lin; Gao, Zhen [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Zhu, Shunxing [Laboratory Animal Center, Nantong University, Nantong, Jiangsu Province (China); Tong, Jian [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Cao, Yi, E-mail: yicao@suda.edu.cn [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China)

    2017-03-15

    Highlights: • Increased reactive oxygen species. • Decreased mitochondrial transcription Factor A and polymerase gamma. • Decreased mitochondrial transcripts (ND1 and 16S) and mtDNA copy number. • Increased 8-hydroxy-2′deoxyguanosine. • Decreased adenosine triphosphate. - Abstract: HL-60 cells, derived from human promyelocytic leukemia, were exposed to continuous wave 900 MHz radiofrequency fields (RF) at 120 μW/cm{sup 2} power intensity for 4 h/day for 5 consecutive days to examine whether such exposure is capable damaging the mitochondrial DNA (mtDNA) mediated through the production of reactive oxygen species (ROS). In addition, the effect of RF exposure was examined on 8-hydroxy-2′-dexoyguanosine (8-OHdG) which is a biomarker for oxidative damage and on the mitochondrial synthesis of adenosine triphosphate (ATP) which is the energy required for cellular functions. The results indicated a significant increase in ROS and significant decreases in mitochondrial transcription factor A, mtDNA polymerase gamma, mtDNA transcripts and mtDNA copy number in RF-exposed cells compared with those in sham-exposed control cells. In addition, there was a significant increase in 8-OHdG and a significant decrease in ATP in RF-exposed cells. The response in positive control cells exposed to gamma radiation (GR, which is also known to induce ROS) was similar to those in RF-exposed cells. Thus, the overall data indicated that RF exposure was capable of inducing mtDNA damage mediated through ROS pathway which also induced oxidative damage. Prior-treatment of RF- and GR-exposed the cells with melatonin, a well-known free radical scavenger, reversed the effects observed in RF-exposed cells.

  13. Damage to Aspergillus fumigatus and Rhizopus oryzae Hyphae by Oxidative and Nonoxidative Microbicidal Products of Human Neutrophils In Vitro

    OpenAIRE

    Diamond, Richard D.; Clark, Robert A.

    1982-01-01

    Our previous studies established that human neutrophils could damage and probably kill hyphae of Aspergillus fumigatus and Rhizopus oryzae in vitro, primarily by oxygen-dependent mechanisms active at the cell surface. These studies were extended, again quantitating hyphal damage by reduction in uptake of 14C-labeled uracil or glutamine. Neither A. fumigatus nor R. oryzae hyphae were damaged by neutrophils from patients with chronic granulomatous disease, confirming the importance of oxidative...

  14. The results of the lipids peroxidation products on the DNA bases as biological markers of the oxidative stress

    International Nuclear Information System (INIS)

    Falletti, O.

    2007-10-01

    Different ways of DNA damages have been studied, among these ones the direct way of DNA damages formation by the reactive oxygen species (R.O.S.). This way leads to the formation of oxidative DNA damages. In 1990, works have suggested an indirect way of DNA damages formation, the lipids peroxidation. Instead of oxidizing directly DNA, the R.O.S. oxide the lipids present in the cells and their membranes; The products coming from this degradation are able to provoke DNA damages. This way has not been studied very much. The work of this thesis is axed on this DNA theme and lipids peroxidation. In the first chapter, we begin by presenting DNA and the direct way of oxidative damages formation by the R.O.S.Then, we speak about the cell lipids suffering oxidation reactions and the different ways of lipids oxidation. Then, we present how the lipid peroxidation is a source of damages for DNA. (N.C.)

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

    International Nuclear Information System (INIS)

    Pinto, A. Viviana; Deodato, Elder L.; Cardoso, Janine S.; Oliveira, Eliza F.; Machado, Sergio L.; Toma, Helena K.; Leitao, Alvaro C.; Padula, Marcelo de

    2010-01-01

    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.

  16. Characterization of oxidative guanine damage and repair in mammalian telomeres.

    Directory of Open Access Journals (Sweden)

    Zhilong Wang

    2010-05-01

    Full Text Available 8-oxo-7,8-dihydroguanine (8-oxoG and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase (OGG1-initiated DNA base excision repair (BER. Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity in mice. The mouse cells were analyzed for telomere integrity by telomere quantitative fluorescence in situ hybridization (telomere-FISH, by chromosome orientation-FISH (CO-FISH, and by indirect immunofluorescence in combination with telomere-FISH and for oxidative base lesions by Fpg-incision/Southern blot assay. In comparison to the wild type, telomere lengthening was observed in Ogg1 null (Ogg1(-/- mouse tissues and primary embryonic fibroblasts (MEFs cultivated in hypoxia condition (3% oxygen, whereas telomere shortening was detected in Ogg1(-/- mouse hematopoietic cells and primary MEFs cultivated in normoxia condition (20% oxygen or in the presence of an oxidant. In addition, telomere length abnormalities were accompanied by altered telomere sister chromatid exchanges, increased telomere single- and double-strand breaks, and preferential telomere lagging- or G-strand losses in Ogg1(-/- mouse cells. Oxidative guanine lesions were increased in telomeres in Ogg1(-/- mice with aging and primary MEFs cultivated in 20% oxygen. Furthermore, oxidative guanine lesions persisted at high level in Ogg1(-/- MEFs after acute exposure to hydrogen peroxide, while they rapidly returned to basal level in wild-type MEFs. These findings indicate that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. Our studies demonstrate that BER pathway is required in repairing oxidative guanine damage in telomeres and maintaining telomere integrity

  17. Experimental study of oxidative DNA damage

    DEFF Research Database (Denmark)

    Loft, Steffen; Deng, Xin-Sheng; Tuo, Jingsheng

    1998-01-01

    Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation of dose-response relationships of carcinogenic and other harmful chemicals and conditions as well as the study of interactions of several factors. So far the effects of more than 50 different chemical ...

  18. Oxidative stress induced inflammation initiates functional decline of tear production.

    Directory of Open Access Journals (Sweden)

    Yuichi Uchino

    Full Text Available Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1 using a modified tetracycline system (Tet-On/Off system. This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b(560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC in humans. The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease.

  19. Inherent health and environmental risk assessment of nanostructured metal oxide production processes.

    Science.gov (United States)

    Torabifard, Mina; Arjmandi, Reza; Rashidi, Alimorad; Nouri, Jafar; Mohammadfam, Iraj

    2018-01-10

    The health and environmental effects of chemical processes can be assessed during the initial stage of their production. In this paper, the Chemical Screening Tool for Exposure and Environmental Release (ChemSTEER) software was used to compare the health and environmental risks of spray pyrolysis and wet chemical techniques for the fabrication of nanostructured metal oxide on a semi-industrial scale with a capacity of 300 kg/day in Iran. The pollution sources identified in each production process were pairwise compared in Expert Choice software using indicators including respiratory damage, skin damage, and environmental damages including air, water, and soil pollution. The synthesis of nanostructured zinc oxide using the wet chemical technique (with 0.523 wt%) leads to lower health and environmental risks compared to when spray pyrolysis is used (with 0.477 wt%). The health and environmental risk assessment of nanomaterial production processes can help select safer processes, modify the operation conditions, and select or modify raw materials that can help eliminate the risks.

  20. Enantioselective oxidative stress and oxidative damage caused by Rac- and S-metolachlor to Scenedesmus obliquus.

    Science.gov (United States)

    Liu, Huijun; Xia, YiLu; Cai, Weidan; Zhang, Yina; Zhang, Xiaoqiang; Du, Shaoting

    2017-04-01

    The rational use and environmental security of chiral pesticides has gained the interest of many researchers. The enantioselective effects of Rac- and S-metolachlor on oxidative stress in Scenedesmus obliquus were determined in this study. Stronger green fluorescence was observed in response to S-metolachlor treatment than to Rac-metolachlor treatment, suggesting that more reactive oxygen species (ROS) were stimulated by S-metolachlor. ROS levels following S-metolachlor treatment were 1.92-, 8.31-, and 1.08-times higher than those observed following Rac-metolachlor treatment at 0.1, 0.2, and 0.3 mg/L, respectively. Superoxide dismutase (SOD) and catalase (CAT) were stimulated with increasing herbicide concentrations, with S-metolachlor exhibiting a greater effect. Oxidative damage in terms of chlorophyll (Chl) content, cellular membrane permeability, and cellular ultrastructures of S. obliquus were investigated. Chla and Chlb contents in algae treated with Rac-metolachlor were 2-6-fold higher than those in algae treated with S-metolachlor at 0.1, 0.2, and 0.3 mg/L. The cellular membrane permeability of algae exposed to 0.3 mg/L Rac- and S-metolachlor was 6.19- and 42.5-times that of the control. Correlation analysis implied that ROS are the major factor responsible for the oxidative damage caused by Rac- and S-metolachlor. Damage to the chloroplasts and cell membrane of S. obliquus, low production of starch granules, and an increased number of vacuoles were observed upon ultrastructural morphology analysis by transmission electron microscope. These results indicate that S-metolachlor has a greater effect on S. obliquus than Rac-metolachlor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2

    Directory of Open Access Journals (Sweden)

    Little Morgan R

    2010-06-01

    Full Text Available Abstract Background Using a murine model of herpes simplex virus (HSV-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis. Methods Purified microglial cell and mixed neural cell cultures were prepared from C57B/6 and TLR2-/- mice. Intracellular ROS production in cultured murine microglia was measured via 2', 7'-Dichlorofluorescin diacetate (DCFH-DA oxidation. An assay for 8-isoprostane, a marker of lipid peroxidation, was utilized to measure free radical-associated cellular damage. Mixed neural cultures obtained from β-actin promoter-luciferase transgenic mice were used to detect neurotoxicity induced by HSV-infected microglia. Results Stimulation with HSV-1 elevated intracellular ROS in wild-type microglial cell cultures, while TLR2-/- microglia displayed delayed and attenuated ROS production following viral infection. HSV-infected TLR2-/- microglia produced less neuronal oxidative damage to mixed neural cell cultures in comparison to HSV-infected wild-type microglia. Further, HSV-infected TLR2-/- microglia were found to be less cytotoxic to cultured neurons compared to HSV-infected wild-type microglia. These effects were associated with decreased activation of p38 MAPK and p42/p44 ERK in TLR2-/- mice. Conclusions These studies demonstrate the importance of microglial cell TLR2 in inducing oxidative stress and neuronal damage in response to viral infection.

  2. Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

    Directory of Open Access Journals (Sweden)

    Leah A. Garcia

    2014-09-01

    Full Text Available Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG. Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1 β, IL-6, IL-10, transforming growth factor β 1 (TGFβ1, and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH oxidase, Myeloperoxidase (MPO, inducible nitric oxide synthase (iNOS, TNF receptor superfamily member 5 (CD40 that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration.

  3. Nickel exposure induces oxidative damage to mitochondrial DNA in Neuro2a cells: the neuroprotective roles of melatonin.

    Science.gov (United States)

    Xu, Shang-Cheng; He, Min-Di; Lu, Yong-Hui; Li, Li; Zhong, Min; Zhang, Yan-Wen; Wang, Yuan; Yu, Zheng-Ping; Zhou, Zhou

    2011-11-01

    Recent studies suggest that oxidative stress and mitochondrial dysfunction play important roles in the neurotoxicity of nickel. Because mitochondrial DNA (mtDNA) is highly vulnerable to oxidative stress and melatonin can efficiently protect mtDNA against oxidative damage in various pathological conditions, the aims of this study were to determine whether mtDNA oxidative damage was involved in the neurotoxicity of nickel and to assay the neuroprotective effects of melatonin in mtDNA. In this study, we exposed mouse neuroblastoma cell lines (Neuro2a) to different concentrations of nickel chloride (NiCl(2), 0.125, 0.25, and 0.5 mm) for 24 hr. We found that nickel significantly increased reactive oxygen species (ROS) production and mitochondrial superoxide levels. In addition, nickel exposure increased mitochondrial 8-hydroxyguanine (8-OHdG) content and reduced mtDNA content and mtDNA transcript levels. Consistent with this finding, nickel was found to destroy mtDNA nucleoid structure and decrease protein levels of Tfam, a key protein component for nucleoid organization. However, all the oxidative damage to mtDNA induced by nickel was efficiently attenuated by melatonin pretreatment. Our results suggest that oxidative damage to mtDNA may account for the neurotoxicity of nickel. Melatonin has great pharmacological potential in protecting mtDNA against the adverse effects of nickel in the nervous system. © 2011 John Wiley & Sons A/S.

  4. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Gurr, J.-R.; Wang, Alexander S.S.; Chen, C.-H.; Jan, K.-Y.

    2005-01-01

    Ultrafine titanium dioxide (TiO 2 ) particles have been shown to exhibit strong cytotoxicity when exposed to UVA radiation, but are regarded as a biocompatible material in the absence of photoactivation. In contrast to this concept, the present results indicate that anatase-sized (10 and 20 nm) TiO 2 particles in the absence of photoactivation induced oxidative DNA damage, lipid peroxidation, and micronuclei formation, and increased hydrogen peroxide and nitric oxide production in BEAS-2B cells, a human bronchial epithelial cell line. However, the treatment with anatase-sized (200 and >200 nm) particles did not induce oxidative stress in the absence of light irradiation; it seems that the smaller the particle, the easier it is for the particle to induce oxidative damage. The photocatalytic activity of the anatase form of TiO 2 was reported to be higher than that of the rutile form. In contrast to this notion, the present results indicate that rutile-sized 200 nm particles induced hydrogen peroxide and oxidative DNA damage in the absence of light but the anatase-sized 200 nm particles did not. In total darkness, a slightly higher level of oxidative DNA damage was also detected with treatment using an anatase-rutile mixture than with treatment using either the anatase or rutile forms alone. These results suggest that intratracheal instillation of ultrafine TiO 2 particles may cause an inflammatory response

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, A. Viviana, E-mail: alicia.pinto@incqs.fiocruz.br [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Deodato, Elder L. [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Cardoso, Janine S. [Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Oliveira, Eliza F.; Machado, Sergio L.; Toma, Helena K. [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Leitao, Alvaro C. [Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Padula, Marcelo de [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil)

    2010-06-01

    Although titanium dioxide (TiO{sub 2}) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO{sub 2} is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO{sub 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{sub 2} associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO{sub 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{sub 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{sub 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{sub 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.

  8. Detection of DNA damage by using hairpin molecular beacon probes and graphene oxide.

    Science.gov (United States)

    Zhou, Jie; Lu, Qian; Tong, Ying; Wei, Wei; Liu, Songqin

    2012-09-15

    A hairpin molecular beacon tagged with carboxyfluorescein in combination with graphene oxide as a quencher reagent was used to detect the DNA damage by chemical reagents. The fluorescence of molecular beacon was quenched sharply by graphene oxide; while in the presence of its complementary DNA the quenching efficiency decreased because their hybridization prevented the strong adsorbability of molecular beacon on graphene oxide. If the complementary DNA was damaged by a chemical reagent and could not form intact duplex structure with molecular beacon, more molecular beacon would adsorb on graphene oxide increasing the quenching efficiency. Thus, damaged DNA could be detected based on different quenching efficiencies afforded by damaged and intact complementary DNA. The damage effects of chlorpyrifos-methyl and three metabolites of styrene such as mandelieaeids, phenylglyoxylieaeids and epoxystyrene on DNA were studied as models. The method for detection of DNA damage was reliable, rapid and simple compared to the biological methods. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Fission product release by fuel oxidation after water ingress

    International Nuclear Information System (INIS)

    Schreiber.

    1990-01-01

    On the basis of data obtained by a literature search, a computer code has been established for the calculation of the degree of oxidation of the fuel in the damaged fuel particles, and hence of the fission product release as a function of the time period of steam ingress. (orig.) [de

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  12. Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation.

    Science.gov (United States)

    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

    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. 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. 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

  13. Oxidative damage in liver after perinatal intoxication with lead and/or cadmium.

    Science.gov (United States)

    Massó, Elvira Luján; Corredor, Laura; Antonio, Maria Teresa

    2007-01-01

    Lead acetate (300 mg Pb/L) and/or cadmium acetate (10mg Cd/L) in blood and liver were administrated as drinking water to pregnant Wistar rats from day 1 of pregnancy to parturition (day 0) or until weaning (day 21), to investigate the toxic effects in blood and in the liver. Both metals produced mycrocitic anaemia in the pups as well as oxidative damage in the liver, as suggested by the significant increase in TBARS production and the high catalase activity. Moreover, intense alkaline and acid phosphatase activity, used as biomarkers of liver adaptation to damaging factors, was observed. In addition, the toxikinetics are different for Pb and Cd: while Cd is a hepatotoxic from day 0, Pb is not until day 21. Finally, simultaneous perinatal administration of both metals seems to protect, at least, in the liver TBARS production against the toxicity produced by Cd or Pb separately.

  14. Cellular defense against singlet oxygen-induced oxidative damage by cytosolic NADP+-dependent isocitrate dehydrogenase.

    Science.gov (United States)

    Kim, Sun Yee; Park, Jeen-Woo

    2003-03-01

    Singlet oxygen (1O2) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. Recently, we have shown that NADP+-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study, we investigated the role of cytosolic form of NADP+-dependent isocitrate dehydrogenase (IDPc) against singlet oxygen-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to singlet oxygen generated from photoactivated dye, the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against singlet oxygen, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against singlet oxygen-induced oxidative injury.

  15. NDE for Characterizing Oxidation Damage in Reinforced Carbon-Carbon

    Science.gov (United States)

    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 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. The results of that study are briefly reviewed in this article as well. Additionally, a short discussion on the future role of simulation to aid in these studies is provided.

  16. Interactions between Biliverdin, Oxidative Damage, and Spleen Morphology after Simulated Aggressive Encounters in Veiled Chameleons.

    Directory of Open Access Journals (Sweden)

    Michael W Butler

    Full Text Available Stressors frequently increase oxidative damage--unless organisms simultaneously mount effective antioxidant responses. One putative mitigative mechanism is the use of biliverdin, an antioxidant produced in the spleen during erythrocyte degradation. We hypothesized that both wild and captive-bred male veiled chameleons (Chamaeleo calyptratus, which are highly aggressive to conspecifics, would respond to agonistic displays with increased levels of oxidative damage, but that increased levels of biliverdin would limit this increase. We found that even just visual exposure to a potential combatant resulted in decreased body mass during the subsequent 48-hour period, but that hematocrit, biliverdin concentration in the bile, relative spleen size, and oxidative damage in plasma, liver, and spleen were unaffected. Contrary to our predictions, we found that individuals with smaller spleens exhibited greater decreases in hematocrit and higher bile biliverdin concentrations, suggesting a revision to the idea of spleen-dependent erythrocyte processing. Interestingly, individuals with larger spleens had reduced oxidative damage in both the liver and spleen, demonstrating the spleen's importance in modulating oxidative damage. We also uncovered differences in spleen size and oxidative damage between wild and captive-bred chameleons, highlighting environmentally dependent differences in oxidative physiology. Lastly, we found no relationship between oxidative damage and biliverdin concentration, calling into question biliverdin's antioxidant role in this species.

  17. Natural plant polyphenols for alleviating oxidative damage in man ...

    African Journals Online (AJOL)

    cumulative effects of oxidative damage over human life span. Current research reveals ... aging, cardiovascular and neurodegenerative diseases [3,4]. .... natural antioxidants and mortality from age- .... health and longevity in normal cells by calorie restriction [63]. ..... H(2)O(2)-induced oxidative stress and senescence via.

  18. Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2016-01-01

    Full Text Available Sirtuin type 1 (SIRT1 belongs to the family of NAD+ dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs, as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP. The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1.

  19. Low Melatonin Production During Adulthood - Phase 2: Association with Levels of Hydroxyl Radical Scavenging and DNA Damage

    National Research Council Canada - National Science Library

    Sobel, Eugene L; Davanipour, Zoreh; Poulsen, Henrik

    2004-01-01

    The primary purpose of the proposed study is to develop cross-sectional evidence concerning whether or not lower melatonin production levels are associated with increased oxidative DNA guanine damage...

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

    International Nuclear Information System (INIS)

    Muniz, Juan F.; McCauley, Linda; Scherer, J.; Lasarev, M.; Koshy, M.; Kow, Y.W.; Nazar-Stewart, Valle; Kisby, G.E.

    2008-01-01

    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 and 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

  1. Early bichemical markers of effects: Enzyme induction, oncogene activation and markers of oxidative damage

    DEFF Research Database (Denmark)

    Poulsen, Henrik E.; Loft, Steffen

    1995-01-01

    Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein......Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein...

  2. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.B.R. Colombo

    2015-01-01

    Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

  3. NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells.

    Directory of Open Access Journals (Sweden)

    Altaf H Sarker

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    Zana, Marianna; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Szabo, Krisztina; Vetro, Agnes; Szucs, Peter; Varkonyi, Agnes; Pakaski, Magdolna; Boda, Krisztina; Rasko, Istvan; Janka, Zoltan; Kalman, Janos

    2006-01-01

    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

  5. Peroxiredoxin 1 Protects Telomeres from Oxidative Damage and Preserves Telomeric DNA for Extension by Telomerase

    Directory of Open Access Journals (Sweden)

    Eric Aeby

    2016-12-01

    Full Text Available Oxidative damage of telomeres can promote cancer, cardiac failure, and muscular dystrophy. Specific mechanisms protecting telomeres from oxidative damage have not been described. We analyzed telomeric chromatin composition during the cell cycle and show that the antioxidant enzyme peroxiredoxin 1 (PRDX1 is enriched at telomeres during S phase. Deletion of the PRDX1 gene leads to damage of telomeric DNA upon oxidative stress, revealing a protective function of PRDX1 against oxidative damage at telomeres. We also show that the oxidized nucleotide 8-oxo-2′deoxyguanosine-5′-triphosphate (8oxodGTP causes premature chain termination when incorporated by telomerase and that some DNA substrates terminating in 8oxoG prevent extension by telomerase. Thus, PRDX1 safeguards telomeres from oxygen radicals to counteract telomere damage and preserve telomeric DNA for elongation by telomerase.

  6. Diminution of Oxidative Damage to Human Erythrocytes and Lymphocytes by Creatine: Possible Role of Creatine in Blood.

    Directory of Open Access Journals (Sweden)

    Neha Qasim

    Full Text Available Creatine (Cr is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Recent reports have shown that Cr displays antioxidant activity which could explain its beneficial cellular effects. We have evaluated the ability of Cr to protect human erythrocytes and lymphocytes against oxidative damage. Erythrocytes were challenged with model oxidants, 2, 2'-azobis(2-amidinopropane dihydrochloride (AAPH and hydrogen peroxide (H2O2 in the presence and absence of Cr. Incubation of erythrocytes with oxidant alone increased hemolysis, methemoglobin levels, lipid peroxidation and protein carbonyl content. This was accompanied by decrease in glutathione levels. Antioxidant enzymes and antioxidant power of the cell were compromised while the activity of membrane bound enzyme was lowered. This suggests induction of oxidative stress in erythrocytes by AAPH and H2O2. However, Cr protected the erythrocytes by ameliorating the AAPH and H2O2 induced changes in these parameters. This protective effect was confirmed by electron microscopic analysis which showed that oxidant-induced cell damage was attenuated by Cr. No cellular alterations were induced by Cr alone even at 20 mM, the highest concentration used. Creatinine, a by-product of Cr metabolism, was also shown to exert protective effects, although it was slightly less effective than Cr. Human lymphocytes were similarly treated with H2O2 in absence and presence of different concentrations of Cr. Lymphocytes incubated with oxidant alone had alterations in various biochemical and antioxidant parameters including decrease in cell viability and induction of DNA damage. The presence of Cr attenuated all these H2O2-induced changes in lymphocytes. Thus, Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase their

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

    Science.gov (United States)

    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

  8. Photoexcited riboflavin induces oxidative damage to human serum albumin

    Science.gov (United States)

    Hirakawa, Kazutaka; Yoshioka, Takuto

    2015-08-01

    Photoexcited riboflavin induced damage of human serum albumin (HSA), a water soluble protein, resulting in the diminishment of fluorescence from the tryptophan residue. Because riboflavin hardly photosensitized singlet oxygen generation and sodium azide, a singlet oxygen quencher, did not inhibit protein damage, electron transfer-mediated oxidation of HSA was speculated. Fluorescence lifetime of riboflavin was not affected by HSA, suggesting that the excited triplet state of riboflavin is responsible for protein damage through electron transfer. In addition, the preventive effect of xanthone derivatives, triplet quenchers, on photosensitized protein damage could be evaluated using this photosensitized reaction system of riboflavin and HSA.

  9. Genetic and environmental influences on oxidative damage assessed in elderly Danish twins

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Ribel-Madsen, Rasmus; Henriksen, Trine

    2011-01-01

    Previous studies have shown an association between oxidative stress and various diseases in humans including cancer, cardiovascular disease, diabetes, and chronic respiratory disease. To what extents this damage is determined by genetic and environmental factors is unknown. In a classical twin...... of oxidative stress were closely correlated (r=0.60-0.84). In conclusion, we demonstrated in a large population of elderly Danish twins that "whole-body" oxidative damage to nucleic acids and lipids is predominantly determined by potentially modifiable nongenetic factors....

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

    Science.gov (United States)

    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 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.

  11. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    International Nuclear Information System (INIS)

    Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Yu, Yingchun; Aschner, Michael

    2009-01-01

    Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F 2 -isoprostanes (F 2 -IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 μM Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E 2 (PGE 2 ). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F 2 -IsoPs and PGE 2 in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

  12. Oxidative stress induced damage in benign and malignant breast diseases: histopathological and biochemical aspects

    Directory of Open Access Journals (Sweden)

    Seema Khanna

    2012-04-01

    Full Text Available Increasing evidences indicate involvement of free radicals in the pathogenesis of benign and malignant breast diseases. Free radicals are highly reactive molecules and react with non–radicals in chain reaction leading to formation of new free radicals. If the defense mechanism of body fails to combat them, these free radicals pose a threat of injuring tissues by reacting with cell lipids. Lipids in the cell membrane undergo degradation to form hydroperoxides, which decompose to form a variety of products including malondialdehyde (MDA. MDA therefore was used as a marker to assess oxidative damage of cells and tissues. The aim of the present study was to assess the status of oxidative stress in the patients of benign and malignant breast diseases. Study has been made on the blood samples of 25 cases of benign breast disease and on an equal number of breast carcinoma patients. 20 healthy subjects were taken as the control cases.Mean MDA levels were significantly raised with depletion of antioxidant activity in all the patients in comparison to their control group suggesting the role of oxidative damage in the aetiopathogenesis of disease.

  13. The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signalling and their interplay

    Directory of Open Access Journals (Sweden)

    James Nathan Cobley

    2015-06-01

    Full Text Available Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1 redox signalling and (2 macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (·OH and hydrogen peroxide (H2O2 as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ·OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

  14. Immunochemical detection of oxidatively damaged DNA

    Czech Academy of Sciences Publication Activity Database

    Rössner ml., Pavel; Šrám, Radim

    2012-01-01

    Roč. 46, č. 4 (2012), s. 492-522 ISSN 1071-5762 R&D Projects: GA MŽP(CZ) SP/1B3/50/07; GA MŠk 2B08005; GA ČR GAP503/11/0084 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : oxidative DNA damage * ELISA * immunohistochemistry Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.279, year: 2012

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

    Science.gov (United States)

    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.

  16. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, B.N. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Lathika, K.M. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Mishra, K.P. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: kpm@magnum.barc.ernet.in

    2006-03-15

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after {gamma}-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  17. Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Aparna Areti

    2014-01-01

    Full Text Available Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

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

    Science.gov (United States)

    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.

  19. Elevated oxidative damage in kitchen workers in Chinese restaurants.

    Science.gov (United States)

    Wang, Jiajia; Luo, Xiaolin; Xu, Bin; Wei, Jun; Zhang, Zhenzhen; Zhu, Huilian

    2011-01-01

    To investigate associations between occupational exposure to cooking oil fumes (COFs) and potential oxidative and genotoxic effects in kitchen workers. Sixty-seven male kitchen workers and 43 male controls from Chinese restaurants in Guangzhou were recruited. For all the participants, the levels of 1-hydroxypyrene (1-OHP) and 8-hydroxy-2-deoxyguanosine (8-oxodG) in urine, binucleated micronucleus (BNMN) frequency, comet tail length and tail DNA% in peripheral blood lymphocytes (PBLs) and malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured. The inhalable particulates (PM(10)) in their workplaces were also monitored. Our results showed that the exposed group had a significantly higher median level of urinary 1-OHP than that of the control group (pkitchen and cooking time per day. All these positive associations remained after adjusting for the four confounders in a subsequent multivariate linear regression analysis. Occupational exposure to COFs led to increased oxidative damage in Chinese kitchen workers. The health consequences of these oxidative changes need further investgation. Urinary 1-OHP and 8-oxodG are noninvasive and effective biomarkers for assessment of oxidative damage in restaurants workers.

  20. Cancer risk and oxidative DNA damage in man

    DEFF Research Database (Denmark)

    Loft, S; Poulsen, H E

    1996-01-01

    with a mechanistically based increased risk of cancer, including Fanconi anemia, chronic hepatitis, cystic fibrosis, and various autoimmune diseases, the biomarker studies indicate an increased rate of oxidative DNA damage or in some instances deficient repair. Human studies support the experimentally based notion...

  1. Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins.

    Science.gov (United States)

    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.

  2. Treatment with glial derived neurotropic factor (GDNF attenuates oxidative damages of spinal

    Directory of Open Access Journals (Sweden)

    Tao Li

    2016-05-01

    Full Text Available Spinal cord injury (SCI is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS, the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also need to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF in addressing the SCI in regard to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentrations was tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p < 0.05. Though treatment with 10 mg/mL and 20 mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.

  3. The effect of obstructive sleep apnea on DNA damage and oxidative stress.

    Science.gov (United States)

    Kang, Il Gyu; Jung, Joo Hyun; Kim, Seon Tae

    2013-06-01

    Obstructive sleep apnea syndrome (OSAS) is associated with repeated hypoxia and re-oxygenation. This characteristic of OSAS may cause oxidative stress and DNA damage. However, the link of OSAS with oxidative stress and DNA damage is still controversial. In the current study, we investigated whether OSAS causes DNA damage using alkaline single-cell gel electrophoresis (comet assay) and measuring oxidative stress by monitoring serum malondialdehyde (MDA) levels. From March 2009 to August 2010, 51 patients who underwent polysomnography (PSG) during the night were enrolled in this study. We obtained serum from the patients at 6 AM. DNA damage and oxidative stress were evaluated using a comet assay and measuring serum MDA, respectively. We divided the patients into two groups according to the existence of comets appearing in the comet assay. Group 1 included 44 patients with negative assay results and group 2 consisted of seven patients with positive comet assay findings. We compared the age, gender proportion, PSG data (respiratory disturbance index [RDI], lowest O2 saturation level, and arousal index [AI]), time of disease onset, smoking habits, and serum MDA levels between the two groups. The average age and gender proportion of the two groups were not statistically different (P>0.05). The average of RDI for group 1 was 30.4±18.4 and 8.0±7.7 (P0.05). No relationship between positive comet assay results and OSAS severity was identified. Results of the current study showed that OSAS was not associated with DNA damage as measured by comet assays or oxidative stress according to serum MDA levels.

  4. Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes

    DEFF Research Database (Denmark)

    Folkmann, Janne K; Risom, Lotte; Jacobsen, Nicklas R

    2009-01-01

    BACKGROUND: C60 fullerenes and single-walled carbon nanotubes (SWCNT) are projected to be used in medicine and consumer products with potential human exposure. The hazardous effects of these particles are expected to involve oxidative stress with generation of oxidatively damaged DNA that might...... be the initiating event in the development of cancer. OBJECTIVE: In this study we investigated the effect of a single oral administration of C60 fullerenes and SWCNT. METHODS: We measured the level of oxidative damage to DNA as the premutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the colon mucosa...... of genotoxicity, whereas corn oil per se generated more genotoxicity than the particles. Although there was increased mRNA expression of 8-oxoguanine DNA glycosylase in the liver of C60 fullerene-treated rats, we found no significant increase in repair activity. CONCLUSIONS: Oral exposure to low doses of C60...

  5. Natural plant polyphenols for alleviating oxidative damage in man ...

    African Journals Online (AJOL)

    prevent the body from oxidative damage over human life span. This review .... Antioxidant supplementation/treatment has been adopted for .... deacetylase family regulates gene silencing and .... Drug News Perspect 2007; 20: 579-. 585. 12.

  6. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  7. Curcumin Attenuates Methotrexate-Induced Hepatic Oxidative Damage in Rats

    International Nuclear Information System (INIS)

    HEMEIDA, R.A.M.; MOHAFEZ, O.M.

    2008-01-01

    In the present study, we have addressed the ability of curcumin to suppress MTX-induced liver damage. Hepatotoxicity was induced by injection of a single dose of MTX (20 mg/kg I.P.). MTX challenge induced liver damage that was well characterized histopathologically and biochemically. MTX increased relative liver/body weight ratio. Histologically, MTX produced fatty changes in hepatocytes and sinusoidal lining cells, mild necrosis and inflammation. Biochemically, the test battery entailed elevated activities of serum ALT and AST. Liver activities of superoxide dismutase (SOD), catalase (CAT) and level of reduced glutathione (GSH), were notably reduced, while lipid peroxidation, expressed as malondialdhyde (MDA) level was significantly increased. Administration of curcumin (100mg/kg, I.P.) once daily for 5 consecutive days after MTX challenge mitigated the injurious effects of MTX and ameliorated all the altered biochemical parameters. These results showed that administration of curcumin decreases MTX-induced liver damage probably via regulation of oxidant/anti-oxidant balance. In conclusion, the present study indicates that curcumin may be of therapeutic benefit against MTX-cytotoxicity.

  8. Oxidative stress and DNA damage induced by imidacloprid in zebrafish (Danio rerio).

    Science.gov (United States)

    Ge, Weili; Yan, Saihong; Wang, Jinhua; Zhu, Lusheng; Chen, Aimei; Wang, Jun

    2015-02-18

    Imidacloprid is a neonicotinoid insecticide that can have negative effects on nontarget animals. The present study was conducted to assess the toxicity of various imidacloprid doses (0.3, 1.25, and 5 mg/mL) on zebrafish sampled after 7, 14, 21, and 28 days of exposure. The levels of catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione-S-transferase (GST), and malondialdehyde (MDA) and the extent of DNA damage were measured to evaluate the toxicity of imidacloprid on zebrafish. SOD and GST activities were noticeably increased during early exposure but were inhibited toward the end of the exposure period. In addition, the CAT levels decreased to the control level following their elevation during early exposure. High concentrations of imidacloprid (1.25 and 5 mg/L) induced excessive ROS production and markedly increased MDA content on the 21st day of exposure. DNA damage was dose- and time-dependent. In conclusion, the present study showed that imidacloprid can induce oxidative stress and DNA damage in zebrafish.

  9. Role of oxidative damage in toxicity of particulates

    DEFF Research Database (Denmark)

    Møller, Peter; Jacobsen, Nicklas R; Folkmann, Janne K

    2010-01-01

    composition play important roles in the oxidative potential of particulates. Studies in animal models indicate that particles from combustion processes (generated by combustion of wood or diesel oil), silicate, titanium dioxide and nanoparticles (C60 fullerenes and carbon nanotubes) produce elevated levels......Particulates are small particles of solid or liquid suspended in liquid or air. In vitro studies show that particles generate reactive oxygen species, deplete endogenous antioxidants, alter mitochondrial function and produce oxidative damage to lipids and DNA. Surface area, reactivity and chemical...

  10. Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: implications for the prevention of methamphetamine-induced neurotoxic damage.

    Science.gov (United States)

    Imam, S Z; Islam, F; Itzhak, Y; Slikker, W; Ali, S F

    2000-09-01

    Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. We have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts.

  11. Biomarkers of oxidative damage to DNA and repair

    DEFF Research Database (Denmark)

    Loft, Steffen; Høgh Danielsen, Pernille; Mikkelsen, Lone

    2008-01-01

    environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer...

  12. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    International Nuclear Information System (INIS)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A.

    2014-01-01

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting

  13. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

    2014-08-05

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

  14. The protective effect of magnesium lithospermate B against glucose-induced intracellular oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Jian [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Xiangya School of Medicine, Changsha 410078 (China); Ren, Xian [Shanghai Green Valley Pharmaceutical Co., Ltd., Shanghai 201304 (China); Hou, Rui-ying; Dai, Xing-ping [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Xiangya School of Medicine, Changsha 410078 (China); Zhao, Ying-chun [Laboratories of Functional Genomics and Proteomics, Creighton University Medical Center, Omaha, NE 68131 (United States); Xu, Xiao-jing; Zhang, Wei; Zhou, Gan; Zhou, Hong-hao [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Xiangya School of Medicine, Changsha 410078 (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Xiangya School of Medicine, Changsha 410078 (China)

    2011-07-22

    Highlights: {yields} LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. {yields} LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. {yields} LAB plays an important role against glucose-induced intracellular oxidative damage. {yields} The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway. -- Abstract: Objectives: To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H{sub 2}O{sub 2}, we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. Materials and methods: The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Results: LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50 {mu}mol/L or 100 {mu}mol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. Conclusions: LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.

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

    Science.gov (United States)

    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.

  16. Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Quan-Guang Zhang

    Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

  17. Pigmented macrophage aggregates as a biomarker of oxidative damage in yellow bullhead catfish, Ameiurus natalis

    International Nuclear Information System (INIS)

    McCreedy, C.D.; HoganEsch, H.; Turek, J.; Jagoe, C.H.

    1995-01-01

    Pigmented macrophage aggregates (PMs) occur when peroxidized lipids resulting from oxidative damage in tissues are scavenged by macrophages. Ionizing radiation causes oxidative damage, so the authors evaluated PMs as a biomarker in the pronephros of yellow bullheads (Ameiurus natalis) inhabiting Pond B, Savannah River Site, SC, a reservoir contaminated with low levels of 137 Cs. ANOVA, ANCOVA, and stepwise regression were used to relate the mean number of PMs, per 0.15 mm 2 of tissue section, to fish sex (females: N = 61; males: N = 84), age (1--6 yrs), body-condition, and muscle 137 Cs concentration. Mean pronephric PMs differed by six and with fish muscle 137 Cs concentration. Among males, PMs were positively correlated with fish age and 137 Cs. In females, PMs were also correlated with fish age and 137 Cs. ANCOVA, with age as covariate, affirmed that sex and muscle 137 Cs were significantly associated with the mean number of pronephric PMs. Using stepwise regression, the interaction of age and 137 Cs concentration was most strongly associated with pronephric PMs in males. Among females, the product of age, body-condition, and 137 Cs concentration was most strongly associated with pronephric PMs. The positive relationships between the number of pronephric PMs and 137 Cs concentration suggest that oxidative damage related to long-term exposure to low-level radiation is detectable in these fish. Secondarily, these results demonstrate the importance of considering covariates such as age and sex when evaluating effects of environmental contaminants

  18. Density of oxidation-induced stacking faults in damaged silicon

    NARCIS (Netherlands)

    Kuper, F.G.; Hosson, J.Th.M. De; Verwey, J.F.

    1986-01-01

    A model for the relation between density and length of oxidation-induced stacking faults on damaged silicon surfaces is proposed, based on interactions of stacking faults with dislocations and neighboring stacking faults. The model agrees with experiments.

  19. Electrolysed reduced water decreases reactive oxygen species-induced oxidative damage to skeletal muscle and improves performance in broiler chickens exposed to medium-term chronic heat stress.

    Science.gov (United States)

    Azad, M A K; Kikusato, M; Zulkifli, I; Toyomizu, M

    2013-01-01

    1. The present study was designed to achieve a reduction of reactive oxygen species (ROS)-induced oxidative damage to skeletal muscle and to improve the performance of broiler chickens exposed to chronic heat stress. 2. Chickens were given a control diet with normal drinking water, or diets supplemented with cashew nut shell liquid (CNSL) or grape seed extract (GSE), or a control diet with electrolysed reduced water (ERW) for 19 d after hatch. Thereafter, chickens were exposed to a temperature of either 34°C continuously for a period of 5 d, or maintained at 24°C, on the same diets. 3. The control broilers exposed to 34°C showed decreased weight gain and feed consumption and slightly increased ROS production and malondialdehyde (MDA) concentrations in skeletal muscle. The chickens exposed to 34°C and supplemented with ERW showed significantly improved growth performance and lower ROS production and MDA contents in tissues than control broilers exposed to 34°C. Following heat exposure, CNSL chickens performed better with respect to weight gain and feed consumption, but still showed elevated ROS production and skeletal muscle oxidative damage. GSE chickens did not exhibit improved performance or reduced skeletal muscle oxidative damage. 4. In conclusion, this study suggests that ERW could partially inhibit ROS-induced oxidative damage to skeletal muscle and improve growth performance in broiler chickens under medium-term chronic heat treatment.

  20. Bicarbonate modulates oxidative and functional damage in ischemia-reperfusion.

    Science.gov (United States)

    Queliconi, Bruno B; Marazzi, Thire B M; Vaz, Sandra M; Brookes, Paul S; Nehrke, Keith; Augusto, Ohara; Kowaltowski, Alicia J

    2013-02-01

    The carbon dioxide/bicarbonate (CO(2)/HCO(3)(-)) pair is the main biological pH buffer. However, its influence on biological processes, and in particular redox processes, is still poorly explored. Here we study the effect of CO(2)/HCO(3)(-) on ischemic injury in three distinct models (cardiac HL-1 cells, perfused rat heart, and Caenorhabditis elegans). We found that, although various concentrations of CO(2)/HCO(3)(-) do not affect function under basal conditions, ischemia-reperfusion or similar insults in the presence of higher CO(2)/HCO(3)(-) resulted in greater functional loss associated with higher oxidative damage in all models. Because the effect of CO(2)/HCO(3)(-) was observed in all models tested, we believe this buffer is an important determinant of oxidative damage after ischemia-reperfusion. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

    Directory of Open Access Journals (Sweden)

    Nevzat Selim Gokay

    2016-01-01

    Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

  2. Protective effects of the extracts of Barringtonia racemosa shoots against oxidative damage in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Kin Weng Kong

    2016-01-01

    Full Text Available Barringtonia racemosa is a tropical plant with medicinal values. In this study, the ability of the water extracts of the leaf (BLE and stem (BSE from the shoots to protect HepG2 cells against oxidative damage was studied. Five major polyphenolic compounds consisting of gallic acid, ellagic acid, protocatechuic acid, quercetin and kaempferol were identified using HPLC-DAD and ESI-MS. Cell viability assay revealed that BLE and BSE were non-cytotoxic (cell viabilities >80% at concentration less than 250 µg/ml and 500 µg/ml, respectively. BLE and BSE improved cellular antioxidant status measured by FRAP assay and protected HepG2 cells against H2O2-induced cytotoxicity. The extracts also inhibited lipid peroxidation in HepG2 cells as well as the production of reactive oxygen species. BLE and BSE could also suppress the activities of superoxide dismutase and catalase during oxidative stress. The shoots of B. racemosa can be an alternative bioactive ingredient in the prevention of oxidative damage.

  3. Arabidopsis mutants lacking phenolic sunscreens exhibit enhanced ultraviolet-B injury and oxidative damage

    International Nuclear Information System (INIS)

    Landry, L.G.; Last, R.L.; Chapple, C.C.S.

    1995-01-01

    We have assessed ultraviolet-B (UV-B)-induced injury in wild-type Arabidopsis thaliana and two mutants with altered aromatic secondary product biosynthesis. Arabidopsis mutants defective in the ability to synthesize UV-B-absorbing compounds (flavonoids in transparent testa 5 [tt5] and sinapate esters in ferulic acid hydroxylase 1 [fah 1]) are more sensitive to UV-B than is the wild-type Landsberg erecta. Despite its ability to accumulate UV-absorptive flavonoid compounds, the ferulic acid hydroxylase mutant fah1 exhibits more physiological injury (growth inhibition and foliar lesions) than either wild type or tt5. The extreme UV-B sensitivity of fah1 demonstrates the importance of hydroxycinnamate esters as UV-B protectants. Consistent with the whole-plant response, the highest levels of lipid and protein oxidation products were seen in fah1. Ascorbate peroxidase enzyme activity was also increased in the leaves of UV-B-treated plants in a dose- and genotype-dependent manner. These results demonstrate that, in A. thaliana, hydryoxycinnamates are more effective UV-B protectants than flavonoids. The data also indicate that A. thaliana responds to UV-B as an oxidative stress, and sunscreen compounds reduce the oxidative damage caused by UV-B. 36 refs., 6 figs

  4. Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions.

    Science.gov (United States)

    Haces, María L; Hernández-Fonseca, Karla; Medina-Campos, Omar N; Montiel, Teresa; Pedraza-Chaverri, José; Massieu, Lourdes

    2008-05-01

    Ketone bodies play a key role in mammalian energy metabolism during the suckling period. Normally ketone bodies' blood concentration during adulthood is very low, although it can rise during starvation, an exogenous infusion or a ketogenic diet. Whenever ketone bodies' levels increase, their oxidation in the brain rises. For this reason they have been used as protective molecules against refractory epilepsy and in experimental models of ischemia and excitotoxicity. The mechanisms underlying the protective effect of these compounds are not completely understood. Here, we studied a possible antioxidant capacity of ketone bodies and whether it contributes to the protection against oxidative damage induced during hypoglycemia. We report for the first time the scavenging capacity of the ketone bodies, acetoacetate (AcAc) and both the physiological and non-physiological isomers of beta-hydroxybutyrate (D- and L-BHB, respectively), for diverse reactive oxygen species (ROS). Hydroxyl radicals (.OH) were effectively scavenged by D- and L-BHB. In addition, the three ketone bodies were able to reduce cell death and ROS production induced by the glycolysis inhibitor, iodoacetate (IOA), while only D-BHB and AcAc prevented neuronal ATP decline. Finally, in an in vivo model of insulin-induced hypoglycemia, the administration of D- or L-BHB, but not of AcAc, was able to prevent the hypoglycemia-induced increase in lipid peroxidation in the rat hippocampus. Our data suggest that the antioxidant capacity contributes to protection of ketone bodies against oxidative damage in in vitro and in vivo models associated with free radical production and energy impairment.

  5. Oxidation products are increased in patients affected by non-segmental generalized vitiligo.

    Science.gov (United States)

    Vaccaro, Mario; Bagnato, Gianluca; Cristani, Mariateresa; Borgia, Francesco; Spatari, Giovanna; Tigano, Valeria; Saja, Antonina; Guarneri, Fabrizio; Cannavò, Serafinella P; Gangemi, Sebastiano

    2017-08-01

    Several lines of evidence support the relevance of reactive oxygen species (ROS) in vitiligo, but the exact role of glycation and oxidation of macromolecules needs to be better addressed. To investigate the involvement of advanced oxidation protein products (AOPPs) and advanced glycation end-products (AGEs), we performed a case-control association study by spectrofluorimetry and spectrophotometry, in 47 patients with non-segmental generalized vitiligo and 47 age- and sex-matched controls. Significantly higher levels of both AOPPs (p vitiligo patients compared to healthy controls. In vitiligo patients, AGEs and AOPPs serum levels were directly associated with extension, duration of vitiligo, and disease activity. ROS, and in particular AGEs and AOPPs, could represent one of the main biomarkers to assess the onset and progression of vitiligo, due to the potential role as direct inducers of cell damage and also as autoimmunity triggers. Further longitudinal studies involving larger cohorts of patients are required to elucidate the role of oxidation products in the pathogenesis of vitiligo.

  6. Single Molecule Scanning of DNA Radiation Oxidative Damage, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal will develop an assay to map genomic DNA, at the single molecule level and in a nanodevice, for oxidative DNA damage arising from radiation exposure;...

  7. The 2100MHz radiofrequency radiation of a 3G-mobile phone and the DNA oxidative damage in brain.

    Science.gov (United States)

    Sahin, Duygu; Ozgur, Elcin; Guler, Goknur; Tomruk, Arın; Unlu, Ilhan; Sepici-Dinçel, Aylin; Seyhan, Nesrin

    2016-09-01

    We aimed to evaluate the effect of 2100MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone on the brain of rats during 10 and 40 days of exposure. The female rats were randomly divided into four groups. Group I; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 2 weeks, group II; control 10 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 2 weeks, group III; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 8 weeks and group IV; control 40 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 8 weeks. After the genomic DNA content of brain was extracted, oxidative DNA damage (8-hydroxy-2'deoxyguanosine, pg/mL) and malondialdehyde (MDA, nmoL/g tissue) levels were determined. Our main finding was the increased oxidative DNA damage to brain after 10 days of exposure with the decreased oxidative DNA damage following 40 days of exposure compared to their control groups. Besides decreased lipid peroxidation end product, MDA, was observed after 40 days of exposure. The measured decreased quantities of damage during the 40 days of exposure could be the means of adapted and increased DNA repair mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells.

    Science.gov (United States)

    Lee, Su Min; Koh, Ho-Jin; Park, Dong-Chan; Song, Byoung J; Huh, Tae-Lin; Park, Jeen-Woo

    2002-06-01

    NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose 6-phosphate dehydrogenase (G6PD), malic enzyme, and the cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc). Little information is available about the role of IDPc in antioxidant defense. In this study we investigated the role of IDPc against cytotoxicity induced by oxidative stress by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 3-4-fold higher and 35% lower, respectively, than that in the parental cells carrying the vector alone. Although the activities of other antioxidant enzymes, such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and G6PD, were comparable in all transformed cells, the ratio of GSSG to total glutathione was significantly higher in the cells expressing the lower level of IDPc. This finding indicates that IDPc is essential for the efficient glutathione recycling. Upon transient exposure to increasing concentrations of H(2)O(2) or menadione, an intracellular source of free radicals and reactive oxygen species, the cells with low levels of IDPc became more sensitive to oxidative damage by H(2)O(2) or menadione. Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against oxidative stress, compared to the control cells. This study provides direct evidence correlating the activities of IDPc and the maintenance of the cellular redox state, suggesting that IDPc plays an important role in cellular defense against oxidative stress.

  9. Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment

    Directory of Open Access Journals (Sweden)

    Sana Chakroun

    2017-12-01

    Full Text Available Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50 given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx. Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01 which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

  10. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  11. Renal damage mediated by oxidative stress: a hypothesis of protective effects of red wine.

    Science.gov (United States)

    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.

  12. Potent effects of alkaloid-rich extract from Huperzia selago against sodium nitroprusside-evoked PC12 cells damage via attenuation of oxidative stress and apoptosis

    Directory of Open Access Journals (Sweden)

    Anna Magdalena Lenkiewicz

    2016-06-01

    Full Text Available Imbalance between production and scavenging of free radicals and other reactive oxygen species (ROS is a component of many diseases, but it is especially important in aging-related diseases of the central nervous system. Oxidative stress-induced neuronal dysfunction plays an important role in the pathomechanism of neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. Experimental data showed that free radical scavengers may protect the brain against oxidative modifications. The need for efficient and safe antioxidants with therapeutic potential stimulated the rise of interest in the medicinal plant products, which are a rich source of phytochemicals possessing biological activity. In our studies we focused on alkaloid fractions (AFs isolated from club moss, Huperzia selago and Diphasiastrum complanatum, due to their beneficial activity and exclusive chemical structure. Our previous study demonstrated that selected alkaloids from Huperzia selago effectively protect macromolecules from oxidative damage. Therefore, in the present study we investigated the effects and mechanisms of action of AFs isolated from Huperzia selago and Diphasiastrum complanatum against sodium nitroprusside (SNP-induced oxidative injury in PC12 cells. The results demonstrated that the selected AFs via reduction of nitric oxide (NO liberation protected cells against oxidative stress, DNA and mitochondrial damage, as well as apoptosis caused by SNP. Selected AF notably decreased SNP-evoked mitochondrial polymerase γ (Polg up-regulation. Furthermore, AF which contains Lycopodine, Serratidine, Lycoposerramine-G and (probably Cermizine B completely inhibited the SNP-induced expression of interferon-γ (Ifng and cyclooxygenase 2 (Ptgs2 as well as significantly down-regulated the expression of 12/15-lipoxygenase (Alox12 and tended to decrease the mRNA level of interleukin-6 gene (Il6. In conclusion, these results suggest that the AFs from Huperzia selago

  13. Radio-oxidative membrane damage and its possible role as an indicator of radiation exposure

    International Nuclear Information System (INIS)

    Amit Kumar; Pandey, B.N.; Mishra, K.P.

    2004-01-01

    Cellular membranes have been recognized as a sensitive target in the mechanism of ionizing radiation-induced cell killing. In our laboratory, studies have been devoted to investigations on gamma radiation induced oxidative damage to model and cellular membrane damage by employing fluorescence and electron spin resonance (ESR) methods Considerable evidences has accumulated to suggest that radiation induced oxidative damage was related to apoptotic death of a variety of cells in culture. Radiation induced damage involving lipid peroxidation, altered bilayer fluidity, permeability changes and intracellular generated ROS have been evaluated by chemical and physical methods. Modification of damage by structural modulating agents such as cholesterol and antioxidants such as eugenol, ascorbic acid, ellagic acid, triphala have been extensively investigated. Generation of intracellular ROS in radiation stressed normal cell e.g. mouse thymocytes, tumor cells e.g. Ehrlich ascites cells and human cervical cell line were evaluated after exposure from low to moderate doses of α-radiation. Results suggest that modulation of intracellular ROS level may be an important approach to alter radio-cytotoxicity of cells. This presentation would describe results of our study together with an overview of free radical mediated oxidative damage to cellular membrane as an indicator of radiation exposure. (author)

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

    Science.gov (United States)

    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.

  15. Spectroellipsometric detection of silicon substrate damage caused by radiofrequency sputtering of niobium oxide

    Science.gov (United States)

    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.

  16. An ECVAG trial on assessment of oxidative damage to DNA measured by the comet assay

    DEFF Research Database (Denmark)

    Johansson, Clara; Møller, Peter; Forchhammer, Lykke

    2010-01-01

    The increasing use of single cell gel electrophoresis (the comet assay) highlights its popularity as a method for detecting DNA damage, including the use of enzymes for assessment of oxidatively damaged DNA. However, comparison of DNA damage levels between laboratories can be difficult due...... to differences in assay protocols (e.g. lysis conditions, enzyme treatment, the duration of the alkaline treatment and electrophoresis) and in the end points used for reporting results (e.g. %DNA in tail, arbitrary units, tail moment and tail length). One way to facilitate comparisons is to convert primary comet...... assay end points to number of lesions/10(6) bp by calibration with ionizing radiation. The aim of this study was to investigate the inter-laboratory variation in assessment of oxidatively damaged DNA by the comet assay in terms of oxidized purines converted to strand breaks with formamidopyrimidine DNA...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    M. Knaś

    2016-01-01

    Full Text Available 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.

  19. Silicon (Si) alleviates cotton (Gossypium hirsutum L.) from zinc (Zn) toxicity stress by limiting Zn uptake and oxidative damage.

    Science.gov (United States)

    Anwaar, Shad Ali; Ali, Shafaqat; Ali, Skhawat; Ishaque, Wajid; Farid, Mujahid; Farooq, Muhammad Ahsan; Najeeb, Ullah; Abbas, Farhat; Sharif, Muhammad

    2015-03-01

    Silicon (Si) is as an important fertilizer element, which has been found effective in enhancing plant tolerance to variety of biotic and a-biotic stresses. This study investigates the Si potential to alleviate zinc (Zn) toxicity stress in cotton (Gossypium hirsutum L.). Cotton plants were grown in hydroponics and exposed to different Zn concentration, 0, 25, and 50 μM, alone and/or in combination with 1 mM Si. Incremental Zn concentration in growth media instigated the cellular oxidative damage that was evident from elevated levels of hydrogen peroxide (H2O2), electrolyte leakage, and malondialdehyde (MDA) and consequently inhibited cotton growth, biomass, chlorophyll pigments, and photosynthetic process. Application of Si significantly suppressed Zn accumulation in various plant parts, i.e., roots, stems, and leaves and thus promoted biomass, photosynthetic, growth parameters, and antioxidant enzymes activity of Zn-stressed as well unstressed plants. In addition, Si reduced the MDA and H2O2 production and electrolyte leakage suggesting its role in protecting cotton plants from Zn toxicity-induced oxidative damage. Thus, the study indicated that exogenous Si application could improve growth and development of cotton crop experiencing Zn toxicity stress by limiting Zn bioavailability and oxidative damage.

  20. Watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice modulates oxidative damage induced by low dose X-ray in mice.

    Science.gov (United States)

    Mohammad, Mohd Khairul Amran; Mohamed, Muhamad Idham; Zakaria, Ainul Mardhiyah; Abdul Razak, Hairil Rashmizal; Saad, Wan Mazlina Md

    2014-01-01

    Watermelon is a natural product that contains high level of antioxidants and may prevent oxidative damage in tissues due to free radical generation following an exposure to ionizing radiation. The present study aimed to investigate the radioprotective effects of watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice against oxidative damage induced by low dose X-ray exposure in mice. Twelve adult male ICR mice were randomly divided into two groups consisting of radiation (Rx) and supplementation (Tx) groups. Rx received filtered tap water, while Tx was supplemented with 50% (v/v) watermelon juice for 28 days ad libitum prior to total body irradiation by 100 μGy X-ray on day 29. Brain, lung, and liver tissues were assessed for the levels of malondialdehyde (MDA), apurinic/apyrimidinic (AP) sites, glutathione (GSH), and superoxide dismutase (SOD) inhibition activities. Results showed significant reduction of MDA levels and AP sites formation of Tx compared to Rx (P watermelon juice restore the intracellular antioxidant activities by significantly increased SOD inhibition activities and GSH levels compared to Rx. These findings may postulate that supplementation of 50% watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice could modulate oxidative damage induced by low dose X-ray exposure.

  1. The Efficiency of Damage Production in Silicon Carbide

    International Nuclear Information System (INIS)

    Weber, William J.; Gao, Fei; Devanathan, Ram; Jiang, Weilin

    2004-01-01

    Molecular dynamics simulations are used to study the statistics of damage production in 3C-SiC due to C, Si and Au primary knock-on atoms (PKAs) over energies from 0.25 to 50 keV. In order to account for the different displacement energies on the Si and C sublattices and accurately assess the damage efficiency, a modified version of the SRIM (Stopping and Range of Ions in Matter) code, with the electronic stopping turned off to duplicate the molecular dynamics conditions, was used to calculate the statistics of damage production for the same PKAs over the energy range from 0.1 to 400 keV under the binary collision approximation using threshold displacement energies of 20 and 35 eV for C and Si, respectively. Using the modified SRIM predictions as a reference, the efficiencies of total damage production are determined for C, Si and Au PKAs as functions of energy. The efficiency for production of C displacements is similar for all PKAs; however, C PKAs have a much lower efficiency for producing stable Si displacements than Si and Au PKAs, which leads to a much higher ratio of C to Si displacements for C PKAs. These results are consistent with the experimental damage production behavior observed in SiC irradiated with C, Si and Au ions at 150 K

  2. The efficiency of damage production in silicon carbide

    International Nuclear Information System (INIS)

    Weber, W.J.; Gao, F.; Devanathan, R.; Jiang, W.

    2004-01-01

    Molecular dynamics (MD) simulations are used to study the statistics of damage production in 3C-SiC due to C, Si and Au primary knock-on atoms (PKAs) over energies from 0.25 to 50 keV. In order to account for the different displacement energies on the Si and C sublattices and accurately assess the damage efficiency, a modified version of the SRIM (stopping and range of ions in matter) code, with the electronic stopping turned off to duplicate the MD conditions, was used to calculate the statistics of damage production for the same PKAs over the energy range from 0.1 to 400 keV under the binary collision approximation using threshold displacement energies of 20 and 35 eV for C and Si, respectively. Using the modified SRIM predictions as a reference, the efficiencies of total damage production are determined for C, Si and Au PKAs as functions of energy. The efficiency for production of C displacements is similar for all PKAs; however, C PKAs have a much lower efficiency for producing stable Si displacements than Si and Au PKAs, which leads to a much higher ratio of C to Si displacements for C PKAs. These results are consistent with the experimental damage production behavior observed in SiC irradiated with C, Si and Au ions at 150 K

  3. Periodontitis and increase in circulating oxidative stress

    Directory of Open Access Journals (Sweden)

    Takaaki Tomofuji

    2009-05-01

    Full Text Available Reactive oxygen species (ROS are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress. Such oxidation may be detrimental to systemic health. For instance, previous animal studies suggested that experimental periodontitis induces oxidative damage of the liver and descending aorta by increasing circulating oxidative stress. In addition, it has been revealed that clinical parameters in chronic periodontitis patients showed a significant improvement 2 months after periodontal treatment, which was accompanied by a significant reduction of reactive oxygen metabolites in plasma. Improvement of periodontitis by periodontal treatment could reduce the occurrence of circulating oxidative stress. Furthermore, recent studies indicate that the increase in circulating oxidative stress following diabetes mellitus and inappropriate nutrition damages periodontal tissues. In such cases, therapeutic approaches to systemic oxidative stress might be necessary to improve periodontal health.

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

    International Nuclear Information System (INIS)

    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

  5. Alpha-Lipoic acid counteracts the promoted oxidative DNA damage in the liver of septic rats

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2006-01-01

    Viral, parasitic infections and chemical carcinogens are among the etiological factors of liver cancer. It seems important to study the initiating and promoting agents to evaluate the etiology and prevention of such life threatening disease. Intestine-derived bacteria product, lipopolysaccharide (LPS), is mainly detoxified by the liver. It has shown to induce a state of oxidative DNA damage is not fully investigated. Increased oxidative DNA damage and rate of cell proliferation may initiate or even promote cancer. In the present work, the capability of LPS to induce 8-hydroxydeoxyguanosine (8-HDG), a specific DNA adduct for oxidative DNA damage, in rat livers is tested. Furthermore, a possible protective effect of alpha lipoic acid (ALA) is also assessed. Investigated parameters are liver contents of glutathione (GSH), lipid peroxides (MDA), nitric oxide (NO) and 8-HDG in the liver-extracted DNA. Serum activities of ALT, AST and GGT as liver-function markers as well as IL2 are assessed. Moreover, liver histology is examined. LPS was given doses of 1, 3, 5, 7 and 9 mg/kg once i.p. while, the rat mortality was examined 24 hours later. ALA was given in doses of 50, 100 and 200 mg/kg once i.p. 3h before LPS is found to be 5mg/kg. LPS increased the level of 8-HDG, MDA and NO in the liver. It also induced acute liver necrosis and inflammatory cell infiltration as shown in liver-histopathology and in the significant increase in the activities of ALT, AST and GGT. LPS increased the serum level of IL2 as well. The dose 200mg/kg of ALA revealed a 100% protection against LPS-induced lethality. It also, prevented the LPS-induced increase in 8-HDG in liver extracted DNA, the liver contents of MDA and NO. ALA also rescued the LPS-induced GSH depletion. It corrected the liver function as shown by the prevention of increases in the activity of ALT, AST and GGT with a remarkable improvement in the liver histology. Moreover, it prevented the increase in serum level of IL2. These

  6. [Occupational hazards, DNA damage, and oxidative stress on exposure to waste anesthetic gases].

    Science.gov (United States)

    Lucio, Lorena M C; Braz, Mariana G; do Nascimento Junior, Paulo; Braz, José Reinaldo C; Braz, Leandro G

    The waste anesthetic gases (WAGs) present in the ambient air of operating rooms (OR), are associated with various occupational hazards. This paper intends to discuss occupational exposure to WAGs and its impact on exposed professionals, with emphasis on genetic damage and oxidative stress. Despite the emergence of safer inhaled anesthetics, occupational exposure to WAGs remains a current concern. Factors related to anesthetic techniques and anesthesia workstations, in addition to the absence of a scavenging system in the OR, contribute to anesthetic pollution. In order to minimize the health risks of exposed professionals, several countries have recommended legislation with maximum exposure limits. However, developing countries still require measurement of WAGs and regulation for occupational exposure to WAGs. WAGs are capable of inducing damage to the genetic material, such as DNA damage assessed using the comet assay and increased frequency of micronucleus in professionals with long-term exposure. Oxidative stress is also associated with WAGs exposure, as it induces lipid peroxidation, oxidative damage in DNA, and impairment of the antioxidant defense system in exposed professionals. The occupational hazards related to WAGs including genotoxicity, mutagenicity and oxidative stress, stand as a public health issue and must be acknowledged by exposed personnel and responsible authorities, especially in developing countries. Thus, it is urgent to stablish maximum safe limits of concentration of WAGs in ORs and educational practices and protocols for exposed professionals. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  7. Pulmonary dysfunctions, oxidative stress and DNA damage in brick kiln workers.

    Science.gov (United States)

    Kaushik, R; Khaliq, F; Subramaneyaan, M; Ahmed, R S

    2012-11-01

    Brick kilns in the suburban areas in developing countries pose a big threat to the environment and hence the health of their workers and people residing around them. The present study was planned to assess the lung functions, oxidative stress parameters and DNA damage in brick kiln workers. A total of 31 male subjects working in brick kiln, and 32 age, sex and socioeconomic status matched controls were included in the study. The lung volumes, capacities and flow rates, namely, forced expiratory volume in first second (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC, expiratory reserve volume, inspiratory capacity (IC), maximal expiratory flow when 50% of FVC is remaining to be expired, maximum voluntary ventilation, peak expiratory flow rate and vital capacity were significantly decreased in the brick kiln workers. Increased oxidative stress as evidenced by increased malonedialdehyde levels and reduced glutathione content, glutathione S-transferase activity and ferric reducing ability of plasma were observed in the study group when compared with controls. Our results indicate a significant correlation between oxidative stress parameters and pulmonary dysfunction, which may be due to silica-induced oxidative stress and resulting lung damage.

  8. Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative Damage in the Liver

    Directory of Open Access Journals (Sweden)

    Y. Li

    2014-06-01

    Full Text Available Alpha-lipoic acid (α-LA is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of α-LA against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1. Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg α-LA supplementation in basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1, for 3 weeks. The results revealed that the addition of 300 mg/kg α-LA protected against the liver function damage of broilers induced by chronic low dose of AFB1 as estimated by a significant (p<0.05 change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the AFB1 diet, but this effect was alleviated by the addition of 300 mg/kg α-LA. Additionally, AFB1 induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with α-LA. Our results suggest that the inhibition of AFB1-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of α-LA against AFB1-induced oxidative damage in the liver.

  9. Field oxide radiation damage measurements in silicon strip detectors

    Energy Technology Data Exchange (ETDEWEB)

    Laakso, M [Particle Detector Group, Fermilab, Batavia, IL (United States) Research Inst. for High Energy Physics (SEFT), Helsinki (Finland); Singh, P; Shepard, P F [Dept. of Physics and Astronomy, Univ. Pittsburgh, PA (United States)

    1993-04-01

    Surface radiation damage in planar processed silicon detectors is caused by radiation generated holes being trapped in the silicon dioxide layers on the detector wafer. We have studied charge trapping in thick (field) oxide layers on detector wafers by irradiating FOXFET biased strip detectors and MOS test capacitors. Special emphasis was put on studying how a negative bias voltage across the oxide during irradiation affects hole trapping. In addition to FOXFET biased detectors, negatively biased field oxide layers may exist on the n-side of double-sided strip detectors with field plate based n-strip separation. The results indicate that charge trapping occurred both close to the Si-SiO[sub 2] interface and in the bulk of the oxide. The charge trapped in the bulk was found to modify the electric field in the oxide in a way that leads to saturation in the amount of charge trapped in the bulk when the flatband/threshold voltage shift equals the voltage applied over the oxide during irradiation. After irradiation only charge trapped close to the interface is annealed by electrons tunneling to the oxide from the n-type bulk. (orig.).

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

    Science.gov (United States)

    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.

  11. Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

    Science.gov (United States)

    Melnyk, Stepan; Fuchs, George J.; Schulz, Eldon; Lopez, Maya; Kahler, Stephen G.; Fussell, Jill J.; Bellando, Jayne; Pavliv, Oleksandra; Rose, Shannon; Seidel, Lisa; Gaylor, David W.

    2012-01-01

    Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism. PMID:21519954

  12. Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway.

    Science.gov (United States)

    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.

  13. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation.

    Science.gov (United States)

    Kang, Kyoung Ah; Lee, Kyoung Hwa; Chae, Sungwook; Zhang, Rui; Jung, Myung Sun; Ham, Young Min; Baik, Jong Seok; Lee, Nam Ho; Hyun, Jin Won

    2006-02-15

    We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway. (c) 2005 Wiley-Liss, Inc.

  14. Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage

    Directory of Open Access Journals (Sweden)

    Jie Deng

    2018-04-01

    Full Text Available Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX. However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine, a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p. significantly inhibited the generation of reactive oxygen species (ROS and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG, and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h. Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arrest

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

    Science.gov (United States)

    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.

  16. Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Poulsen, Henrik Enghusen; Kessing, Lars Vedel

    2015-01-01

    OBJECTIVES: The pathophysiological mechanisms underlying bipolar disorder and its multi-system nature are unclear. Oxidatively generated damage to nucleosides has been demonstrated in metabolic disorders; however, the extent to which this occurs in bipolar disorder in vivo is unknown. We...... investigated oxidatively generated damage to DNA and RNA in patients with bipolar disorder and its relationship with the affective phase compared with healthy control subjects. METHODS: Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), markers...... of oxidatively generated DNA and RNA damage, respectively, was measured in 37 rapid cycling patients with bipolar disorder and in 40 age- and gender-matched healthy control subjects. Employing a longitudinal design, repeated measurements of both markers were evaluated in various affective phases in patients...

  17. Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

    Science.gov (United States)

    Huong, Nguyen Thi Thu; Murakami, Yukihisa; Tohda, Michihisa; Watanabe, Hiroshi; Matsumoto, Kinzo

    2005-08-01

    Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.

  18. Quantification of in vivo oxidative damage in Caenorhabditis elegans during aging by endogenous F3-isoprostane measurement

    NARCIS (Netherlands)

    Labuschagne, C.F.; Stigter, E.C.; Hendriks, M.M.; Berger, R.; Rokach, J.; Korswagen, H.C.; Brenkman, A.B.

    2013-01-01

    Oxidative damage is thought to be a major cause in development of pathologies and aging. However, quantification of oxidative damage is methodologically difficult. Here, we present a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach for accurate, sensitive, and linear in vivo

  19. Synergistic Application of Black Tea Extracts and Lactic Acid Bacteria in Protecting Human Colonocytes against Oxidative Damage.

    Science.gov (United States)

    Zhao, Danyue; Shah, Nagendra P

    2016-03-23

    In view of the potential of lactic acid bacteria (LAB) to enhance the antioxidant activity of food products, this work explored the effectiveness of LAB fermented black tea samples in alleviating H2O2-induced oxidative stress in human colonocytes. The antioxidant capacity of tea samples was evaluated in terms of cyto-protectiveness, mitochondria membrane potential (Δψm)-stabilizing activity, ROS-inhibitory effect, and antioxidant enzyme-modulating activity. The effect on oxidative DNA damage and repair was studied in CCD 841 by comet assay. Results showed that the protective effect of tea pretreatment was more pronounced in normal cells (CCD 841) than in carcinomas (Caco-2), and fermented samples were invariably more effective. Higher cell viability and Δψm were maintained and ROS production was markedly inhibited with tea pretreatment. The fermented tea samples also remarkably stimulated DNA repair, resulting in fewer strand breaks and oxidative lesions. Our study implied that LAB fermentation may be an efficient way to enhance the antioxidative effectiveness of black tea flavonoid-enriched foods.

  20. Protective Effect of Nitric Oxide (NO against Oxidative Damage in Larix gmelinii Seedlings under Ultraviolet-B Irradiation

    Directory of Open Access Journals (Sweden)

    Haiqing Hu

    2016-10-01

    Full Text Available Ultraviolet-B (UV-B stress appears to be more striking than other research works because of the thin ozone layer. The protective influence of an exogenous nitric oxide donor and sodium nitroprusside (SNP on the growth properties of Larix gmelinii seedlings was investigated under ultraviolet-B radiation conditions. The results indicated that 0.1 mM SNP could effectively alleviate the damage caused by ultraviolet-B radiation, and improved the seedling growth properties, the relative water content, and photosynthetic pigment content in leaves. Additionally, the photosynthetic capacity and antioxidant enzyme activity were increased during the exposure. On the contrary, the damage caused by active oxygen was decreased in SNP-treated seedling leaves. The damage caused by ultraviolet-B radiation was slightly reduced after treating with 0.01 mM SNP. Nevertheless, treatment with 0.5 mM SNP had a negative effect under ultraviolet-B radiation. Furthermore, supplementing NO (nitric oxide improved the photosynthetic capacity and antioxidant enzyme activity and alleviated the damage of caused by active oxygen. The best effective concentration of SNP was 0.1 mM. Therefore, a suitable amount of exogenous NO can protect the Larix gmelinii seedlings and increase their tolerance to ultraviolet-B radiation.

  1. Modelling of Zircaloy-steam-oxidation under severe fuel damage conditions

    International Nuclear Information System (INIS)

    Malang, S.; Neitzel, H.J.

    1983-01-01

    Small break loss-of-coolant accidents and special transients in an LWR, in combination with loss of required safety systems, may lead to an uncovered core for an extended period of time. As a consequence, the cladding temperature could rise up to the melting point due to the decay heat, resulting in severely damaged fuel rods. During heat-up the claddings oxidize due to oxygen uptake from the steam atmosphere in the core. The modeling and assessment of the Zircaloy-steam oxidation under such conditions is important, mainly for two reasons: The oxidation of the cladding influences the temperature transients due to the exothermic heat of reaction; the amount of liquified fuel depends on the oxide layer thickness and the oxygen content of the remaining Zircaloy metal when the melting point is reached. (author)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  4. Pulsed electric field improves the bioprotective capacity of purées for different coloured carrot cultivars against H2O2-induced oxidative damage.

    Science.gov (United States)

    Leong, Sze Ying; Oey, Indrawati; Burritt, David John

    2016-04-01

    This research aimed to study the effect of pulsed electric field (PEF) processing on the bioprotective capacity of carrot purée for White Belgian, Yellow Solar, Nantes, Nutri Red and Purple Haze cultivars against H2O2-induced oxidative damage. The bioprotective capacity was determined using cell viability, membrane integrity and nitric oxide (NO) production in a human Caco-2 cell culture assay. Total carotenoids, total anthocyanins, total vitamin C and total phenolics were also evaluated. Compared to the untreated purée, Purple Haze and Nutri Red processed at 303 kJ/kg completely increased Caco-2 cells resistance towards oxidative damage by recovering the cell viability and inhibiting NO production. For cultivar with low carotenoid levels, i.e. Yellow Solar, the application of 0.8 kV/cm resulted in a higher total carotenoid content in the purée than its untreated counterpart, leading to an improved bioprotective effect. This study clearly shows that PEF could add value to carrots by maximising bioprotective effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Oxidative Damage in Erythrocytes During Cold Storage With Organ Preservation Solution

    OpenAIRE

    MEMMEDOĞLU, Akif B.

    1999-01-01

    It is known that erythrocyte aggregation in renal tissue during preserva-tion is cause of microcirculation defects in the reperfusion period. The aim of our study is to investigate oxidative damage in erythrocytes relative to the time of cold ischemia during organ preservation and relationship between lipid peroxidation and development of these damages. In experiments with a rabbit model, explanted kidneys were exposed to perfusion and 96 hours preservation with Euro-Collins (EC) in the 1...

  6. Environmental ozone exposure and oxidative DNA damage in adult residents of Florence, Italy

    Energy Technology Data Exchange (ETDEWEB)

    Palli, Domenico, E-mail: d.palli@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Sera, Francesco, E-mail: f.sera@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Giovannelli, Lisa, E-mail: lisag@pharm.unifi.i [Department of Pharmacology, University of Florence, Viale G.Pieraccini 6, 50139 Florence (Italy); Masala, Giovanna, E-mail: g.masala@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Grechi, Daniele [Regional Environmental Protection Agency of Tuscany (ARPAT), Via Porpora 22, 50144 Florence (Italy); Bendinelli, Benedetta, E-mail: b.bendinelli@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Caini, Saverio, E-mail: s.caini@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Dolara, Piero, E-mail: piero.dolara@unifi.i [Department of Pharmacology, University of Florence, Viale G.Pieraccini 6, 50139 Florence (Italy); Saieva, Calogero, E-mail: c.saieva@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy)

    2009-05-15

    In 71 adults residing in Florence, Italy, enrolled in a prospective study, we investigated the correlation between individual levels of oxidative DNA damage detected by the Comet assay in circulating lymphocytes, and a specific ozone exposure score calculated in 10 different time-windows (0-5 to 0-90 days) before blood drawing, based on daily measurements provided by the local environmental monitoring system. Overall, statistically significant positive correlations between average ozone concentrations and DNA damage emerged in almost all time-windows considered; correlations were more evident among males, non-smokers, and traffic-exposed workers. Multivariate regression analyses taking into account selected individual characteristics, showed an independent effect on DNA damage of average ozone concentrations in the last 60-90 days before blood drawing. Local residents showed a divergent pattern with correlations restricted to shorter time-windows. Our results suggest that ozone concentrations at ground levels modulate oxidative DNA damage in circulating lymphocytes of residents of polluted areas. - Ozone concentrations over the 60-90 days before blood drawing correlated with DNA damage in circulating lymphocytes of adults living in the metropolitan area of Florence, Italy.

  7. Environmental ozone exposure and oxidative DNA damage in adult residents of Florence, Italy

    International Nuclear Information System (INIS)

    Palli, Domenico; Sera, Francesco; Giovannelli, Lisa; Masala, Giovanna; Grechi, Daniele; Bendinelli, Benedetta; Caini, Saverio; Dolara, Piero; Saieva, Calogero

    2009-01-01

    In 71 adults residing in Florence, Italy, enrolled in a prospective study, we investigated the correlation between individual levels of oxidative DNA damage detected by the Comet assay in circulating lymphocytes, and a specific ozone exposure score calculated in 10 different time-windows (0-5 to 0-90 days) before blood drawing, based on daily measurements provided by the local environmental monitoring system. Overall, statistically significant positive correlations between average ozone concentrations and DNA damage emerged in almost all time-windows considered; correlations were more evident among males, non-smokers, and traffic-exposed workers. Multivariate regression analyses taking into account selected individual characteristics, showed an independent effect on DNA damage of average ozone concentrations in the last 60-90 days before blood drawing. Local residents showed a divergent pattern with correlations restricted to shorter time-windows. Our results suggest that ozone concentrations at ground levels modulate oxidative DNA damage in circulating lymphocytes of residents of polluted areas. - Ozone concentrations over the 60-90 days before blood drawing correlated with DNA damage in circulating lymphocytes of adults living in the metropolitan area of Florence, Italy.

  8. Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Poulsen, Henrik E; Weimann, Allan

    2009-01-01

    Oxidatively generated damage to nucleic acids is considered to play a significant role in carcinogenesis, and it has been shown that people with hereditary hemochromatosis are at increased risk of cancer. In this study we used a new refined liquid chromatography-tandem mass spectrometry method...... of the iron overload seen in this disease. By this mechanism cellular damage resulting in end organ damage, typically seen in the liver of such patients, may be mediated....

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

    Science.gov (United States)

    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.

  10. Pomegranate Alleviates Oxidative Damage and Neurotransmitter Alterations in Rats Brain Exposed to Aluminum Chloride and/or Gamma Radiation

    International Nuclear Information System (INIS)

    Said, U.Z.; EL-Tahawey, N.A.; Elassal, A.A.; Elsayed, E.M.; Shousha, W.Gh.

    2013-01-01

    Aluminum and gamma radiation, both are potent neurotoxins and have been implicated in many human neuro degenerative diseases. The present study was designed to investigate the role of pomegranate in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to aluminum chloride (AlCl 3 ), and/or gamma radiation (IR). The results revealed that rats whole body exposed to γ- rays, (1 Gy/week up to 4 Gy), and/or administered aluminum chloride (35 mg/kg body weight), via gavages for 4 weeks, resulted in brain tissue damage, featuring by significant increase of the level of thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP), associated with significant decrease of superoxide dismutase (SOD) and catalase (CAT) activities, as well as glutathione (GSH) content indicating occurrence of oxidative stress. A significant decrease of serotonin (5-HT) level associated with a significant increase of 5-hydroxyindole acetic acid (5-HIAA), in addition to a significant decrease in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents recorded at the 1st, 7th and 14th day post-irradiation, indicating alterations in the metabolism of brain monoamines. On the other hand, the results exhibited that, supplementation of rats with pomegranate, via gavages, at a dose of 3 ml /kg body weight/ day, for 4 weeks along with AlCl 3 with or without radiation has significantly ameliorated the changes occurred in the mentioned parameters and the values returned close to the normal ones. It could be concluded that pomegranate, by its antioxidant constituents might antagonize brain oxidative damage and minimize the severity of aluminum (Al), and/or radiation-induced neurotransmitters disorders

  11. Modulation of oxidative damage by nitroxide free radicals.

    Science.gov (United States)

    Dragutan, Ileana; Mehlhorn, Rolf J

    2007-03-01

    Piperidine nitroxides like 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) are persistent free radicals in non-acidic aqueous solutions and organic solvents that may have value as therapeutic agents in medicine. In biological environments, they undergo mostly reduction to stable hydroxylamines but can also undergo oxidation to reactive oxoammonium compounds. Reactions of the oxoammonium derivatives could have adverse consequences including chemical modification of vital macromolecules and deleterious effects on cell signaling. An examination of their reactivity in aqueous solution has shown that oxoammonium compounds can oxidize almost any organic as well as many inorganic molecules found in biological systems. Many of these reactions appear to be one-electron transfers that reduce the oxoammonium to the corresponding nitroxide species, in contrast to a prevalence of two-electron reductions of oxoammonium in organic solvents. Amino acids, alcohols, aldehydes, phospholipids, hydrogen peroxide, other nitroxides, hydroxylamines, phenols and certain transition metal ions and their complexes are among reductants of oxoammonium, causing conversion of this species to the paramagnetic nitroxide. On the other hand, thiols and oxoammonium yield products that cannot be detected by ESR even under conditions that would oxidize hydroxylamines to nitroxides. These products may include hindered secondary amines, sulfoxamides and sulfonamides. Thiol oxidation products other than disulfides cannot be restored to thiols by common enzymatic reduction pathways. Such products may also play a role in cell signaling events related to oxidative stress. Adverse consequences of the reactions of oxoammonium compounds may partially offset the putative beneficial effects of nitroxides in some therapeutic settings.

  12. High-Intensity Exercise Induced Oxidative Stress and Skeletal Muscle Damage in Postpubertal Boys and Girls: A Comparative Study.

    Science.gov (United States)

    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 exercise level at 24 and 48 hours after exercise in both the sexes, (p 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.

  13. Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes.

    Science.gov (United States)

    Dutta, Eryn H; Behnia, Faranak; Boldogh, Istvan; Saade, George R; Taylor, Brandie D; Kacerovský, Marian; Menon, Ramkumar

    2016-02-01

    In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation. Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM. Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups. Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence. Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM. Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome. This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of

  14. Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

    Directory of Open Access Journals (Sweden)

    Dilek Pandir

    2016-01-01

    Full Text Available Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ-induced diabetic rat kidney. At the end of the experimental period (28 days, we found that lycopene markedly decreased the malondialdehide (MDA levels in the kidney, urea, uric acid and creatinine levels in the serum of furan-treated rats. The increase of histopathology in the kidney of furan-treated rats were effectively suppressed by lycopene. Furthermore, lycopene markedly restored superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and glutathione-S-transferase (GST activities in the kidney of furan-treated rats. In conclusion, these results suggested that lycopene could protect the rat kidney against furan-induced injury by improving renal function, attenuating histopathologic changes, reducing MDA production and renewing the activities of antioxidant enzymes.

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

    Science.gov (United States)

    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

  16. Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage

    Science.gov (United States)

    Redgrove, Kate A.; McLaughlin, Eileen A.

    2017-01-01

    In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte. PMID:29312475

  17. Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage

    Science.gov (United States)

    Barrett, Caitlyn W.; Reddy, Vishruth K.; Short, Sarah P.; Motley, Amy K.; Lintel, Mary K.; Bradley, Amber M.; Freeman, Tanner; Vallance, Jefferson; Ning, Wei; Parang, Bobak; Poindexter, Shenika V.; Fingleton, Barbara; Chen, Xi; Washington, Mary K.; Wilson, Keith T.; Shroyer, Noah F.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

    2015-01-01

    Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions. PMID:26053663

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

    Science.gov (United States)

    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.

  19. Ganoderma extract prevents albumin-induced oxidative damage and chemokines synthesis in cultured human proximal tubular epithelial cells.

    Science.gov (United States)

    Lai, Kar Neng; Chan, Loretta Y Y; Tang, Sydney C W; Leung, Joseph C K

    2006-05-01

    Ganoderma lucidum (Ganoderma or lingzhi) is widely used as an alternative medicine remedy to promote health and longevity. Recent studies have indicated that components extracted from Ganoderma have a wide range of pharmacological actions including suppressing inflammation and scavenging free radicals. We recently reported that tubular secretion of interleukin-8 (IL-8) induced by albumin is important in the pathogenesis of tubulointerstitial injury in the proteinuric state. In this study, we explored the protective effect of Ganoderma extract (LZ) on albumin-induced kidney epithelial injury. Growth arrested human proximal tubular epithelial cells (PTECs) were incubated with 0.625 to 10 mg/ml human serum albumin (HSA) for up to 72 h. HSA induced DNA damage and apoptosis in PTEC in a dose- and time-dependent manner. Co-incubation of PTEC with 4-64 microg/ml LZ significantly reduced the oxidative damage and cytotoxic effect of HSA in a dose-dependent manner (PGanoderma (16 microg/ml). To explore the components of LZ that exhibited most protective effect in HSA-induced PTEC damages, LZ was further separated into two sub-fractions, LZF1 (MW effective in reducing sICAM-1 released from HSA-activated PTEC whereas the high molecular weight LZ (unfractionated LZ) was more effective in diminishing IL-8 production. Our results suggest that Ganoderma significantly reduces oxidative damages and apoptosis in PTEC induced by HSA. The differential reduction of IL-8 or sICAM-1 released from HSA-activated PTEC by different components of the LZ implicates that components of Ganoderma with different molecular weights could play different roles and operate different mechanisms in preventing HSA-induced PTEC damage.

  20. Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver

    DEFF Research Database (Denmark)

    Sørensen, Mette; Jensen, B.R.; Poulsen, Henrik E.

    2001-01-01

    and catalase activity was also assessed in the kidneys. In order to examine a possible effect of the Brussels sprouts related to oxidative stress, we measured oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and lipid peroxidation in terms of malondialdehyde (MDA) formation...... on MDA levels were found. The present results support the data obtained in several studies that consumption of cruciferous vegetables is capable of inducing various phase II enzyme systems. However, the observed increase in oxidative DNA damage raises the question of whether greatly increased ingestion...

  1. Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

    Science.gov (United States)

    Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

    2016-01-01

    Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.

  2. Assessment of DNA damage and oxidative stress induced by radiation in Eisenia fetida

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2012-04-15

    Exposure of eukaryotic cells to ionizing radiation results in the immediate formation of free radicals and the occurrence of oxidative cell damage. Recently International Commission on Radiological Protection (ICRP) requires the effect data of ionizing radiation on non-human biota for the radiological protection of the environment. Based on their radioecological properties and their important role in the soil ecosystem, earthworms have been identified by the ICRP as one of the reference animals and plants (RAPs) to be used in environmental radiation protection. The investigation shows that oxidative stress is closely related to the exposed dose of radiation in the environment. To evaluate oxidative stress by ionizing radiation in the earthworm, we performed several experiments. The comet assay is known as a measurement which is one of the best techniques in assessing the DNA damage by oxidative stress. The SOD is a key enzyme in protecting cells against oxidative stress. An increase in the level of antioxidant enzyme such as SOD indicated that the exposure to radiation caused stress responses. Glutathione oxidation is considered as a maker for detection of reactive oxygen species (ROS). The GSSG levels increased progressively with increased exposure dose of ionizing radiation, which suggested a dose-dependent ROS generation.

  3. Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients

    Directory of Open Access Journals (Sweden)

    Vaishali Kolgiri Honnapurmath

    2017-01-01

    Full Text Available Background and Objectives: Insulin resistance (IR is frequent in human immunodeficiency virus (HIV infection and may be related to antiretroviral therapy (ART. Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA damage in HIV-1-infected patients with different ART status. Materials and Methods: In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG, as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment. Results: All subjects were randomly selected and grouped as HIV-negative (control group (n = 300, HIV-positive without ART (n = 100, HIV-positive with ART first line (n = 100, and HIV-positive with ART second line (n = 100. IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509 P < 0.001. Interpretation and Conclusions: In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

  4. Deformability of Erythrocytes and Oxidative Damage in Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Mukerrem Betul Yerer

    2012-04-01

    Full Text Available Purpose: A lowered cerebral perfusion as a consequence of hemodynamic microcirculatory insufficiency is one of the factors underlying in Alzheimer's disease, which is a neurodegenerative disorder leading to progressive cognitive impairment. Erythrocyte deformability is one of the major factors affecting the microcirculatory hemodynamics which is closely related to the oxidative damage. The aim of this study is to investigate the relationship between the erythrocyte deformability, nitric oxide levels and oxidative stress in Alzheimer's disease. Methods: The blood samples of 30 elderly people in three groups consisting of healthy control and different severities of the disease (low and severe were used. Then the erythrocytes were isolated and the deformability of erythrocytes was determined by Rheodyne SSD evaluating the elongation indexes of the erythrocytes under different shear stress. The catalase, glutathione peroxidase and plasma nitric oxide levels were measured spectrophotometric ally. Results: The plasma nitric oxide levels, catalase activities were found significantly higher and glutathione peroxidase activity was significantly lower in severe Alzheimer's disease patients compared to the control group. However, the deformability of erythrocytes was not significantly affected from these alterations. Conclusion: the oxidant-antioxidant status is dramatically changed in Alzheimer's disease patients with the severity of the disease and similar alterations were seen in the nitric oxide levels without any significant change in erythrocyte deformability. [Cukurova Med J 2012; 37(2.000: 65-75

  5. Green Synthesized Zinc Oxide (ZnO) Nanoparticles Induce Oxidative Stress and DNA Damage in Lathyrus sativus L. Root Bioassay System.

    Science.gov (United States)

    Panda, Kamal K; Golari, Dambaru; Venugopal, A; Achary, V Mohan M; Phaomei, Ganngam; Parinandi, Narasimham L; Sahu, Hrushi K; Panda, Brahma B

    2017-05-18

    Zinc oxide nanoparticles (ZnONP-GS) were synthesised from the precursor zinc acetate (Zn(CH₃COO)₂) through the green route using the milky latex from milk weed ( Calotropis gigantea L. R. Br) by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich) and cationic Zn 2+ from Zn(CH₃COO)₂ were tested in a dose range of 0-100 mg·L -1 for their potency (i) to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O₂ •- , H₂O₂ and • OH), cell death, and lipid peroxidation; (ii) to modulate the activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), guaiacol peroxidase (GPX), and ascorbate peroxidase (APX); and (iii) to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn 2+ alone.

  6. Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

    International Nuclear Information System (INIS)

    Lundby, Carsten; Pilegaard, Henriette; Hall, Gerrit van; Sander, Mikael; Calbet, Jose; Loft, Steffen; Moeller, Peter

    2003-01-01

    Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle biopsies from seven healthy humans were obtained at sea level and after 2 and 8 weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by quantitative RT-PCR of mRNA levels did not significantly change during high-altitude hypoxia, although the data could not exclude a minor upregulation. The expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite increased generation of oxidative DNA damage

  7. Guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    The Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked by the European Food Safety Authority (EFSA) t to draft guidance on scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health. This guidance has been drawn from scientific...... opinions of the NDA Panel on such health claims. Thus, this guidance document represents the views of the NDA Panel based on the experience gained to date with the evaluation of health claims in these areas. It is not intended that the document should include an exhaustive list of beneficial effects...

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

    Directory of Open Access Journals (Sweden)

    Annemarie Grindel

    Full Text Available 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

  9. ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.

    Science.gov (United States)

    Berger, N Daniel; Stanley, Fintan K T; Moore, Shaun; Goodarzi, Aaron A

    2017-10-05

    Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

  10. Increased urinary excretion of 8-oxo-2'-deoxyguanosine, a biomarker of oxidative DNA damage, in urban bus drivers

    DEFF Research Database (Denmark)

    Loft, S; Poulsen, H E; Vistisen, K

    1999-01-01

    Oxidative damage to DNA could be involved in the increased risk of cancer associated with exposure to polluted urban air, which contains a number of oxidants. CYP1A2 is induced by and metabolizes polyaromatic hydrocarbons (PAH) and aromatic amines and could modify effects of exposure to ambient air...... pollution. Similarly, DNA repair may be influenced by occupational and other exposures as well as modify the effect of DNA damaging agents. As part of a large investigation of the genotoxic burden to diesel exposed workers in transport sectors we studied oxidative DNA damage in 57 non-smoking bus drivers...... from the greater Copenhagen area. The drivers were studied on a workday and on a day off work. Comparisons were made between drivers from the central (n=30) and rural/suburban (n=27) areas of Copenhagen. The rate of oxidative DNA damage was estimated from 24 h urinary excretion of 8-oxo-2...

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

    Science.gov (United States)

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

    2016-10-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Oxidation damage evaluation by non-destructive method for graphite components in high temperature gas-cooled reactor

    International Nuclear Information System (INIS)

    Shibata, Taiju; Tada, Tatsuya; Sumita, Junya; Sawa, Kazuhiro

    2008-01-01

    To develop non-destructive evaluation methods for oxidation damage on graphite components in High Temperature Gas-cooled Reactors (HTGRs), the applicability of ultrasonic wave and micro-indentation methods were investigated. Candidate graphites, IG-110 and IG-430, for core components of Very High Temperature Reactor (VHTR) were used in this study. These graphites were oxidized uniformly by air at 500degC. The following results were obtained from this study. (1) Ultrasonic wave velocities with 1 MHz can be expressed empirically by exponential formulas to burn-off, oxidation weight loss. (2) The porous condition of the oxidized graphite could be evaluated with wave propagation analysis with a wave-pore interaction model. It is important to consider the non-uniformity of oxidized porous condition. (3) Micro-indentation method is expected to determine the local oxidation damage. It is necessary to assess the variation of the test data. (author)

  13. Oxidative DNA damage in vitamin C-supplemented guinea pigs after intratracheal instillation of diesel exhaust particles

    DEFF Research Database (Denmark)

    Moller, P.; Daneshvar, B.; Loft, S.

    2003-01-01

    . The concentrations of ascorbate in liver, lung, and plasma were unaltered by the DEP exposure. The results indicate that in guinea pigs DEP causes oxidative DNA damage rather than bulky DNA adducts in the lung. Guinea pigs, which are similar to humans with respect to vitamin C metabolism, may serve as a new model...... for the study of oxidative damage induced by particulate matter. (C) 2003 Elsevier Science (USA). All rights reserved....

  14. Grape (Vitis vinifera) extracts protect against radiation-induced oxidative stress and DNA damage

    International Nuclear Information System (INIS)

    Singha, Indrani; Das, Subir Kumar; Saxena, S.; Gautam, S.

    2016-01-01

    Ionizing radiation (IR) causes oxidative stress through the overwhelming generation of reactive oxygen species (ROS) in the living cells leading further to the oxidative damage to biomolecules. Grapes (Vitis vinifera) contain several bioactive phytochemicals and are the richest source of antioxidant. In this study, we investigated and compared in vitro antioxidant activity and DNA damage protective property of the grape extracts of four different cultivars, including the Thompson seedless, Flame seedless, Kishmish chorni and Red globe. The activities of ascorbic acid oxidase and catalase significantly (p<0.01) differed among extracts within the same cultivar, while that of peroxidase and polyphenol oxidase did not differ significantly among extracts of any cultivar. In vitro antioxidant activities were assessed by ferric-reducing antioxidant power (FRAP) assay and ABTS. The superoxide radical-scavenging activity was higher in the seed as compared to the skin or pulp of the same cultivar. DNA damage was evaluated in acellular system using pBR322 plasmid relaxation. Grape extract was able to effectively scavenge free radicals in vitro. It could significantly prevent radiation-induced DNA damage. Furthermore, the protective action of grape depends on the source of extract and type of the cultivars. (author)

  15. Oxidative damage to biological macromolecules in Prague bus drivers and garagemen: impact of air pollution and genetic polymorphisms.

    Science.gov (United States)

    Bagryantseva, Yana; Novotna, Bozena; Rossner, Pavel; Chvatalova, Irena; Milcova, Alena; Svecova, Vlasta; Lnenickova, Zdena; Solansky, Ivo; Sram, Radim J

    2010-11-10

    DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 15-F(2t)-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher levels of DNA instability and oxidative damage to biological macromolecules than the controls. The incidence of oxidized lesions in lymphocyte DNA, but not the urinary levels of 8-oxodG, correlated with exposure to benzene and triglycerides increased this damage. Oxidative damage to lipids and proteins was associated with exposure to cPAHs and the lipid peroxidation levels positively correlated with age and LDL cholesterol, and negatively with vitamin C. The carriers of at least one variant hOGG1 (Cys) allele tended to higher oxidative damage to lymphocyte DNA than those with the wild genotype, while XPD23 (Gln/Gln) homozygotes were more susceptible to the induction of DNA strand breaks. In contrast, GSTM1 null variant seemed to protect DNA integrity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

    Directory of Open Access Journals (Sweden)

    Kennedy Hugh

    2008-10-01

    Full Text Available Abstract Background Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. Methods We examined telomere length (by flow fluorescent in situ hybridization and oxidative DNA damage (flow cytometry of 8 – oxoguanosine in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9% and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. Results Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5. Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7. There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1. Conclusion Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism.

  17. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.......Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA...

  18. [Oxidative damage effects induced by CdTe quantum dots in mice].

    Science.gov (United States)

    Xie, G Y; Chen, W; Wang, Q K; Cheng, X R; Xu, J N; Huang, P L

    2017-07-20

    Objective: To investigate Oxidative damage effects induced by CdTe Quantum Dots (QDs) in mice. Methods: 40 ICR mice were randomly divided into 5 groups: one control group (normal saline) ; four CdTe QDs (exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 0、0.5、5.0、50.0 and 500.0 nmol/ml respectively) . After 24 h, the mice were decapitated and the blood was collected for serum biochemically indexes、hematology indexes, the activities of SOD、GSH-Px and the concentration of MDA were all detected. Results: The results showed in the four CdTe QDs exposure groups, the level of CRE、PLT and the concentration of MDA were all significantly lower than those of the control group ( P control group ( P <0.01) . Conclusion: It was suggested that CdTe QDs at 0.5 nmol/ml could induce Oxidative damage effects in mice.

  19. Green Synthesized Zinc Oxide (ZnO Nanoparticles Induce Oxidative Stress and DNA Damage in Lathyrus sativus L. Root Bioassay System

    Directory of Open Access Journals (Sweden)

    Kamal K. Panda

    2017-05-01

    Full Text Available Zinc oxide nanoparticles (ZnONP-GS were synthesised from the precursor zinc acetate (Zn(CH3COO2 through the green route using the milky latex from milk weed (Calotropis gigantea L. R. Br by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX, transmission electron microscopy (TEM, and X-ray diffraction (XRD. Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich and cationic Zn2+ from Zn(CH3COO2 were tested in a dose range of 0–100 mg·L−1 for their potency (i to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O2•−, H2O2 and •OH, cell death, and lipid peroxidation; (ii to modulate the activities of antioxidant enzymes: catalase (CAT, superoxide dismutase (SOD, guaiacol peroxidase (GPX, and ascorbate peroxidase (APX; and (iii to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn2+ alone.

  20. Personal exposure to ultrafine particles and oxidative DNA damage

    DEFF Research Database (Denmark)

    Vinzents, Peter S; Møller, Peter; Sørensen, Mette

    2005-01-01

    10), nitrous oxide, nitrogen dioxide, carbon monoxide, and/or number concentration of UFPs at urban background or busy street monitoring stations was not a significant predictor of DNA damage, although personal UFP exposure was correlated with urban background concentrations of CO and NO2...... the morning after exposure measurement. Cumulated outdoor and cumulated indoor exposures to UFPs each were independent significant predictors of the level of purine oxidation in DNA but not of strand breaks. Ambient air concentrations of particulate matter with an aerodynamic diameter of ..., particularly during bicycling in traffic. The results indicate that biologic effects of UFPs occur at modest exposure, such as that occurring in traffic, which supports the relationship of UFPs and the adverse health effects of air pollution....

  1. Periodontitis and increase in circulating oxidative stress

    OpenAIRE

    Takaaki Tomofuji; Koichiro Irie; Toshihiro Sanbe; Tetsuji Azuma; Daisuke Ekuni; Naofumi Tamaki; Tatsuo Yamamoto; Manabu Morita

    2009-01-01

    Reactive oxygen species (ROS) are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress). Such oxidation may be detrimental to systemic health. Fo...

  2. Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism.

    Science.gov (United States)

    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.

  3. Doxycycline reduces nitric oxide production in guinea pig inner ears.

    Science.gov (United States)

    Helling, Kai; Wodarzcyk, Karl; Brieger, Jürgen; Schmidtmann, Irene; Li, Huige; Mann, Wolf J; Heinrich, Ulf-Rüdiger

    2011-12-01

    Gentamicin application is an important therapeutic option to control vertigo spells in Ménière's disease. However, even in the case of low-dose intratympanic application, gentamicin might contribute to a pathological NO-increase leading to cochlear damage and hearing impairment. The study was performed to evaluate the nitric oxide (NO) reducing capacity of doxycycline in the inner ear after NO-induction by gentamicin. In a prospective animal study, a single dose of gentamicin (10mg/kg body weight) was injected intratympanically into male guinea pigs (n=48). The auditory brainstem responses (ABRs) were recorded prior to application and 3, 5 and 7 days afterwards. The organ of Corti and the lateral wall of 42 animals were isolated after 7 days and incubated separately for 6h in cell culture medium. Doxycycline was adjusted to organ cultures of 5 animals. Two NOS inhibitors, N(G)-Nitro-l-arginine methyl ester (l-NAME) and NG-monomethyl-l-arginine monoacetate (l-NMMA), were applied in three different concentrations to the organ cultures of 30 animals in total (5 animals per concentration). As controls, seven animals received no further substance except gentamicin. The NO-production was quantified by chemiluminescence. Additional six gentamicin-treated animals were used for immunohistochemical studies. The ABRs declined continuously from the first to the seventh day after gentamicin application. Doxycycline reduced NO-production in the lateral wall by 54% (p=.029) comparable to the effect of the applied nitric oxide inhibitors. In the organ of Corti, NO-production was reduced by about 41% showing no statistical significance in respect to great inter-animal variations. The application of doxycycline might offer a new therapeutic approach to prevent NO-induced cochlea damage through ototoxic substances. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. [Endonuclease modified comet assay for oxidative DNA damage induced by detection of genetic toxicants].

    Science.gov (United States)

    Zhao, Jian; Li, Hongli; Zhai, Qingfeng; Qiu, Yugang; Niu, Yong; Dai, Yufei; Zheng, Yuxin; Duan, Huawei

    2014-03-01

    The aim of this study was to investigate the use of the lesion-specific endonucleases-modified comet assay for analysis of DNA oxidation in cell lines. DNA breaks and oxidative damage were evaluated by normal alkaline and formamidopyrimidine-DNA-glycosylase (FPG) modified comet assays. Cytotoxicity were assessed by MTT method. The human bronchial epithelial cell (16HBE) were treated with benzo (a) pyrene (B(a)P), methyl methanesulfonate (MMS), colchicine (COL) and vincristine (VCR) respectively, and the dose is 20 µmol/L, 25 mg/ml, 5 mg/L and 0.5 mg/L for 24 h, respectively. Oxidative damage was also detected by levels of reactive oxygen species in treated cells. Four genotoxicants give higher cytotoxicity and no significant changes on parameters of comet assay treated by enzyme buffer. Cell survival rate were (59.69 ± 2.60) %, (54.33 ± 2.81) %, (53.11 ± 4.00) %, (51.43 ± 3.92) % in four groups, respectively. There was the direct DNA damage induced by test genotoxicants presented by tail length, Olive tail moment (TM) and tail DNA (%) in the comet assay. The presence of FPG in the assays increased DNA migration in treated groups when compared to those without it, and the difference was statistically significant which indicated that the clastogen and aneugen could induce oxidative damage in DNA strand. In the three parameters, the Olive TM was changed most obviously after genotoxicants treatment. In the contrast group, the Olive TM of B(a) P,MMS, COL,VCR in the contrast groups were 22.99 ± 17.33, 31.65 ± 18.86, 19.86 ± 9.56 and 17.02 ± 9.39, respectively, after dealing with the FPG, the Olive TM were 34.50 ± 17.29, 43.80 ± 10.06, 33.10 ± 12.38, 28.60 ± 10.53, increased by 58.94%, 38.48%, 66.86% and 68.21%, respectively (t value was 3.91, 3.89, 6.66 and 3.87, respectively, and all P comet assay appears more specific for detecting oxidative DNA damage induced by genotoxicants exposure, and the application of comet assay will be expanded. The endonuclease

  5. Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-κB signaling in cultured astrocytes

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Hussein, Mohamed Hamed; Kato, Shin; Suzuki, Satoshi; Ito, Tetsuya; Togari, Hajime; Asai, Kiyofumi

    2009-01-01

    Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor-α and interferon-γ, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-κB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-κB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-κB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.

  6. Oxidatively damaged DNA in animals exposed to particles

    DEFF Research Database (Denmark)

    Møller, Peter; Danielsen, Pernille Høgh; Jantzen, Kim

    2013-01-01

    on optimal methods. The majority of studies have used single intracavitary administration or inhalation with dose rates exceeding the pulmonary overload threshold, resulting in cytotoxicity and inflammation. It is unclear whether this is relevant for the much lower human exposure levels. Still...... not be equivocally determined. Roles of cytotoxicity or inflammation for oxidatively induced DNA damage could not be documented or refuted. Studies on exposure to particles in the gastrointestinal tract showed consistently increased levels of 8-oxo-7,8-dihydroguanine in the liver. Collectively, there is evidence...

  7. Oxidative Damage, Inflammation, and Toll-Like Receptor 4 Pathway Are Increased in Preeclamptic Patients: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Fabiana C. B. Bernardi

    2012-01-01

    Full Text Available Problem. There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE patients. Method of Study. 33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls, inflammatory response (interleukin-6 and myeloperoxidase activity, and activation of the TLR-4-NF-kB pathway. Results. An increase of IL-6 levels in both plasma and placenta was observed, but myeloperoxidase activity was not significantly different comparing the groups. Oxidative damage parameters were increased in plasma and placenta in PE patients. A significant increase of the protein levels of TLR-4 and NF-kB was observed in the placenta. Conclusion. The TLR4-NF-kB pathway is upregulated in PE, probably generating local and systemic inflammatory response that is followed by local and systemic oxidative damage.

  8. Chrysin Administration Protects against Oxidative Damage in Varicocele-Induced Adult Rats

    Directory of Open Access Journals (Sweden)

    Gabriela Missassi

    2017-01-01

    Full Text Available Oxidative stress is known as the leading factor responsible for varicocele-related infertility and for that reason, many antioxidant therapies have been proposed. Considering that, we evaluated the reproductive outcomes and fertility of varicocelized rats and the impact of chrysin within these parameters. The animals were allocated into three groups: sham (control, varicocele treated via gavage with 50 mg/kg/day of chrysin (V1, or vehicle (V2 for 56 days. Chrysin treatment prevented oxidative damage resulting from varicocele by decreasing testicular concentrations of malondialdehyde and sperm DNA fragmentation. It also improved histological aspect of the testis and maintained morphometric parameters similar to the sham group. Furthermore, there were no differences in body and reproductive organ weights, histopathological analysis of epididymis, sperm counts and morphology, testosterone levels, sexual behavior, and fertility parameters among experimental groups. Our results reinforce the idea that injuries provoked by experimental varicocele are related, at least in part, to oxidative stress. Moreover, varicocele showed bilateral deleterious effects without interfering with fertility. Chrysin administration significantly ameliorated sperm parameters, protecting the reproductive system against varicocele damages. For that reason, chrysin might be an alternative adjuvant therapy to improve sperm quality in men presenting this condition.

  9. Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

    Directory of Open Access Journals (Sweden)

    T. RODRIGUES

    2009-01-01

    Full Text Available

    Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR, trifluoperazine (TFP and fluphenazine (FP on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the prooxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems. Keywords: Trifluoperazine, thioridazine, fluphenazine, rat liver mitochondria, oxidative stress, photochemistry, photodamage, respiratory chain.

  10. Effect of Thai banana (Musa AA group) in reducing accumulation of oxidation end products in UVB-irradiated mouse skin.

    Science.gov (United States)

    Leerach, Nontaphat; Yakaew, Swanya; Phimnuan, Preeyawass; Soimee, Wichuda; Nakyai, Wongnapa; Luangbudnark, Witoo; Viyoch, Jarupa

    2017-03-01

    Chronic UVB exposure causes skin disorders and cancer through DNA strand breaks and oxidation of numerous functional groups of proteins and lipids in the skin. In this study, we investigated the effects of Thai banana (Musa AA group, "Khai," and Musa ABB group, "Namwa") on the prevention of UVB-induced skin damage when fed to male ICR mice. Mice were orally fed banana (Khai or Namwa) fruit pulps at dose of 1mg/g body weight/day for 12weeks. The shaved backs of the mice were irradiated with UVB for 12weeks. The intensity dose of UVB-exposure was increased from 54mJ/cm 2 /exposure at week 1 to 126mJ/cm 2 /exposure at week 12. A significant increase in skin thickness, lipid peroxidation, protein oxidation end products, and expression of MMP-1 was observed in UVB-irradiated mouse skin. A reduction in the accumulation of oxidation end products was found in the skin of UVB-irradiated mice receiving Khai. This occurred in conjunction with a reduction in MMP-1 expression, inhibition of epidermal thickening, and induction of γ-GCS expression. The dietary intake of Khai prevented skin damage from chronic UVB exposure by increased γ-GCS expression and reduced oxidation end products included carbonyls, malondialdehyde and 4-hydroxynonenal. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  12. Nitroxides are more efficient inhibitors of oxidative damage to calf skin collagen than antioxidant vitamins.

    Science.gov (United States)

    Venditti, Elisabetta; Scirè, Andrea; Tanfani, Fabio; Greci, Lucedio; Damiani, Elisabetta

    2008-01-01

    Reactive oxygen species generated upon UV-A exposure appear to play a major role in dermal connective tissue transformations including degradation of skin collagen. Here we investigate on oxidative damage to collagen achieved by exposure to (i) UV-A irradiation and to (ii) AAPH-derived radicals and on its possible prevention using synthetic and natural antioxidants. Oxidative damage was identified through SDS-PAGE, circular dichroism spectroscopy and quantification of protein carbonyl residues. Collagen (2 mg/ml) exposed to UV-A and to AAPH-derived radicals was degraded in a time- and dose-dependent manner. Upon UV-A exposure, maximum damage was observable at 730 kJ/m2 UV-A, found to be equivalent to roughly 2 h of sunshine, while exposure to 5 mM AAPH for 2 h at 50 degrees C lead to maximum collagen degradation. In both cases, dose-dependent protection was achieved by incubation with muM concentrations of nitroxide radicals, where the extent of protection was shown to be dictated by their structural differences whereas the vitamins E and C proved less efficient inhibitors of collagen damage. These results suggest that nitroxide radicals may be able to prevent oxidative injury to dermal tissues in vivo alternatively to commonly used natural antioxidants.

  13. Female plumage colour influences seasonal oxidative damage and testosterone profiles in a songbird.

    Science.gov (United States)

    Vitousek, Maren N; Stewart, Rosemary A; Safran, Rebecca J

    2013-10-23

    Across diverse taxa, morphological traits mediate social interactions and mate selection. Physiological constraints on signal elaboration have been widely documented, but the potential for trait display to influence physiological state remains poorly understood. We tested for the presence of causal links between ventral plumage colour-a trait known to covary with reproductive performance-and physiological measures in female North American barn swallows, Hirundo rustica erythrogaster. Naturally darker swallows have lower levels of plasma oxidative damage. Females manipulated to display darker ventral plumage during reproduction rapidly decreased oxidative damage, adopting the physiological state of naturally darker individuals. These results support the presence of a social mechanism that links static plumage traits with the physiological state of their bearer during trait advertisement, long after the completion of signal development.

  14. Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC Damages.

    Directory of Open Access Journals (Sweden)

    Yumei Zhang

    Full Text Available Here, we studied the underlying mechanism of aldosterone (Aldo-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L inhibited human umbilical vein endothelial cells (HUVEC survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18 production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P, an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS inhibitor PDMP or the ceramide (C6 potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1 is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

  15. Assessment of evidence for nanosized titanium dioxide-generated DNA strand breaks and oxidatively damaged DNA in cells and animal models

    DEFF Research Database (Denmark)

    Møller, Peter; Jensen, Ditte Marie; Wils, Regitze Sølling

    2017-01-01

    Nanosized titanium dioxide (TiO2) has been investigated in numerous studies on genotoxicity, including comet assay endpoints and oxidatively damaged DNA in cell cultures and animal models. The results have been surprisingly mixed, which might be attributed to physico-chemical differences...... culture studies also demonstrate increased levels of oxidatively damaged DNA after exposure to TiO2. There are relatively few studies on animal models where DNA strand breaks and oxidatively damaged DNA have been tested with reliable methods. Collectively, this review shows that exposure to nanosized TiO2...... of the tested TiO2. In the present review, we assess the role of certain methodological issues and publication bias. The analysis shows that studies on DNA strand breaks without proper assay controls or very low intra-group variation tend to show statistically significant effects. Levels of oxidatively damaged...

  16. 2- and 4-Aminobiphenyls induce oxidative DNA damage in human hepatoma (Hep G2) cells via different mechanisms

    International Nuclear Information System (INIS)

    Wang Shuchi; Chung, Jing-Gung; Chen, C.-H.; Chen, S.-C.

    2006-01-01

    4-Aminobiphenyl (4-ABP) and its analogue, 2-aminobiphenyl (2-ABP), were examined for their ability to induce oxidative DNA damage in Hep G2 cells. Using the alkaline comet assay, we showed that 2-ABP and 4-ABP (25-200 μM) were able to induce the DNA damage in Hep G2 cells. With both compounds, formation of intracellular reactive oxygen species (ROS) was detected using flow cytometry analysis. Post-treatment of 2-ABP and 4-ABP-treated cells by endonuclease III (Endo III) or formamidopyrimidine-DNA glycosylase (Fpg) to determine the formation of oxidized pyrimidines or oxidized purines showed a significant increase of the extent of DNA migration. This indicated that oxidative DNA damage occurs in Hep G2 cells after exposure to 2-ABP and 4-ABP. This assumption was further substantiated by the fact that the spin traps, 5,5-dimethyl-pyrroline-N-oxide (DMPO) and N-tert-butyl-α-phenylnitrone (PBN), decreased DNA damage significantly. Furthermore, addition of the catalase (100 U/ml) caused a decrease in the DNA damage induced by 2-ABP or 4-ABP, indicating that H 2 O 2 is involved in ABP-induced DNA damage. Pre-incubation of the cells with the iron chelator desferrioxamine (DFO) (1 mM) and with the copper chelator neocupronine (NC) (100 μM) also decreased DNA damage in cells treated with 200 μM 2-ABP or 200 μM 4-ABP, while the calcium chelator {1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester}(BAPTA/AM) (10 μM) decreased only DNA strand breaks in cells exposed to 4-ABP. This suggested that ions are involved in the formation of DNA strand breaks. Using RT-PCR and Western blotting, lower inhibition of the expression of the OGG1 gene and of the OGG1 protein was observed in cells treated with 4-ABP, and 2-ABP-treated cells showed a marked reduction in the expression of OGG1 gene and OGG1 protein. Taken together, our finding indicated the mechanisms of induced oxidative DNA damage in Hep G2 cell by 2-ABP and 4-ABP are different, although both

  17. Exogenous nitric oxide improves salt tolerance during establishment of Jatropha curcas seedlings by ameliorating oxidative damage and toxic ion accumulation.

    Science.gov (United States)

    Gadelha, Cibelle Gomes; Miranda, Rafael de Souza; Alencar, Nara Lídia M; Costa, José Hélio; Prisco, José Tarquinio; Gomes-Filho, Enéas

    2017-05-01

    Jatropha curcas is an oilseed species that is considered an excellent alternative energy source for fossil-based fuels for growing in arid and semiarid regions, where salinity is becoming a stringent problem to crop production. Our working hypothesis was that nitric oxide (NO) priming enhances salt tolerance of J. curcas during early seedling development. Under NaCl stress, seedlings arising from NO-treated seeds showed lower accumulation of Na + and Cl - than those salinized seedlings only, which was consistent with a better growth for all analyzed time points. Also, although salinity promoted a significant increase in hydrogen peroxide (H 2 O 2 ) content and membrane damage, the harmful effects were less aggressive in NO-primed seedlings. The lower oxidative damage in NO-primed stressed seedlings was attributed to operation of a powerful antioxidant system, including greater glutathione (GSH) and ascorbate (AsA) contents as well as catalase (CAT) and glutathione reductase (GR) enzyme activities in both endosperm and embryo axis. Priming with NO also was found to rapidly up-regulate the JcCAT1, JcCAT2, JcGR1 and JcGR2 gene expression in embryo axis, suggesting that NO-induced salt responses include functional and transcriptional regulations. Thus, NO almost completely abolished the deleterious salinity effects on reserve mobilization and seedling growth. In conclusion, NO priming improves salt tolerance of J. curcas during seedling establishment by inducing an effective antioxidant system and limiting toxic ion and reactive oxygen species (ROS) accumulation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells

    International Nuclear Information System (INIS)

    Kamp, Hennicke G.; Eisenbrand, Gerhard; Schlatter, Josef; Wuerth, Kirsten; Janzowski, Christine

    2005-01-01

    Ochratoxin A (OTA) is a nephrotoxic/-carcinogenic mycotoxin, produced by several Aspergillus- and Penicillium-strains. Humans are exposed to OTA via food contamination, a causal relationship of OTA to human endemic Balkan nephropathy is still under debate. Since DNA-adducts of OTA or its metabolites could not be identified unambiguously, its carcinogenic effectiveness might be related to secondary effects, such as oxidative cell damage or cell proliferation. In this study, OTA mediated induction of (oxidative) DNA damage, cytotoxicity (necrosis, growth inhibition, apoptosis) and modulation of glutathione were investigated in cell lines (V79, CV-1) and primary rat kidney cells. After 24 h incubation, viability of V79 cells was strongly decreased by OTA concentrations >2.5 μmol/L, whereas CV-1 cells were clearly less sensitive. Strong growth inhibition occurred in both cell lines (IC 50 ∼2 μmol/L). Apoptosis, detected with an immunochemical test and with flow cytometry, was induced by >1 μmol/L OTA. Oxidative DNA damage, detected by comet assay after additional treatment with repair enzymes, was induced in all cell systems already at five-fold lower concentrations. Glutathione in CV-1 cells was depleted after 1 h incubation (>100 μmol/L). In contrast, an increase was measured after 24 h incubation (>0.5 μmol/L). In conclusion, OTA induces oxidative DNA damage at low, not yet cytotoxic concentrations. Oxidative DNA damage might initiate cell transformation eventually in connection with proliferative response following cytotoxic cell death. Both events might represent pivotal factors in the chain of cellular events leading into nephro-carcinogenicity of OTA

  19. Metoprolol induces oxidative damage in common carp (Cyprinus carpio).

    Science.gov (United States)

    Martínez-Rodríguez, Héctor; Donkor, Kingsley; Brewer, Sharon; Galar-Martínez, Marcela; SanJuan-Reyes, Nely; Islas-Flores, Hariz; Sánchez-Aceves, Livier; Elizalde-Velázquez, Armando; Gómez-Oliván, Leobardo Manuel

    2018-04-01

    During the last decade, β-blockers such as metoprolol (MTP) have been frequently detected in surface water, aquatic systems and municipal water at concentrations of ng/L to μg/L. Only a small number of studies exist on the toxic effects induced by this group of pharmaceuticals on aquatic organisms. Therefore, the present study aimed to evaluate the oxidative damage induced by MTP in the common carp Cyprinus carpio, using oxidative stress biomarkers. To this end, indicators of cellular oxidation such as hydroperoxide content (HPC), lipid peroxidation (LPX) and protein carbonyl content (PCC) were determined, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Also, concentrations of MTP and its metabolite O-desmethyl metoprolol were determined in water as well as carp gill, liver, kidney, brain and blood, along with the partial uptake pattern of these compounds. Results show that carp takes up MTP and its metabolite in the different organs evaluated, particularly liver and gill. The oxidative stress biomarkers, HPC, LPX, and PCC, as well as SOD and CAT activity all increased significantly at most exposure times in all organs evaluated. Results indicate that MTP and its metabolite induce oxidative stress on the teleost C. carpio and that the presence of these compounds may constitute a risk in water bodies for aquatic species. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel.

    Science.gov (United States)

    Cheng, Yung-Hsin; Lin, Feng-Huei; Wang, Chien-Ying; Hsiao, Chen-Yuan; Chen, Hung-Ching; Kuo, Hsin-Yu; Tsai, Ting-Fen; Chiou, Shih-Hwa

    2016-10-01

    Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    OpenAIRE

    Kna?, M.; Maciejczyk, M.; Daniszewska, I.; Klimiuk, A.; Matczuk, J.; Ko?odziej, U.; Waszkiel, D.; ?adny, J. R.; ?endzian-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...

  2. Oxidative DNA as related to cancer and aging

    International Nuclear Information System (INIS)

    Ames, B.N.

    1987-01-01

    DNA damage in man can result from a variety of endogenous processes. Of particular importance as endogenous processes may be metabolic pathways that generate oxygen radicals and other reactive oxygen species. Oxygen radicals have been shown to produce DNA base damage and strand breaks. Two products that are formed in DNA in vitro by chemical oxidation or ionizing radiation (and oxidative mutagen) are thymine glycol and hydroxymethyl-uracil, both oxidation products of thymine. Specific mammalian DNA repair systems are known to excise these lesions from DNA in vitro. The authors' laboratory has recently reported the identification, in both human and rat urine, of thymine glycol, thymidine glycol, and hydroxymethyluracil. They now have considerable evidence that these products are derived from the repair of oxidized DNA. The total output of these three compounds represents the formation of about 1,000 oxidized thymine residues per cell per day in man. Since these products are only three of a considerable number of types of oxidative DNA damage products described by radiobiologists, there are likely to be several thousand oxidative DNA hits per cell per day in man. Rats, which have a higher specific metabolic rate and a shorter life span, excrete about 15 times more thymine glycol, thymidine glycol, and hydroxymethyluracil per kilogram body weight. The authors also describe new methods for measuring the levels, which are considerable, of hydrogen peroxide and lipid hydroperoxides in normal plasma and tissues. These non-invasive assays of DNA and other oxidation products may allow the direct testing of current theories that relate oxidative metabolism to the processes of cancer and aging in man

  3. Chemical Characterization and Reactivity Testing of Fuel-Oxidizer Reaction Product (Test Report)

    Science.gov (United States)

    1996-01-01

    reactions of FORP compositions used in this study were unremarkable, Neither the various compositions of FORP, the pure major components of FORP, nor mixtures of FORP with propellant-system corrosion products showed any unusual thermal activity when decomposed under laboratory conditions. Off-limit thruster operations were simulated by rapid mixing of liquid MMH and liquid NTO in a confined space. The test hardware was constructed with pressure- and temperature-measurement devices to determine if the expected fuel oxidizer reaction would result in increased energy release when FORP, FORP constituents, or propellant-system corrosion products were present. These tests demonstrated that FORP, MMHN, AN, or Inconel corrosion products can induce a mixture of MMH and NTO to produce component-damaging energies. The simulation-test program was not extensive enough to provide statistical probabilities for these events but did show that such events can occur. Damaging events required FORP or metal salts to be present at the initial mixing of MMH and NTO. Based on the results of these studies, it is suggested that removal or mitigation of a buildup of these materials may decrease the incidence of these high-energy, potentially damaging events.

  4. Damage recovery and optical activity in europium implanted wide gap oxides

    International Nuclear Information System (INIS)

    Alves, E.; Marques, C.; Franco, N.; Alves, L.C.; Peres, M.; Soares, M.J.; Monteiro, T.

    2010-01-01

    In this study we compare and discuss the defects and optical behaviour of sapphire and magnesium oxide single crystals implanted at room temperature with different fluences (1 x 10 15 -1 x 10 16 cm -2 ) of europium ions. Rutherford backscattering channelling shows that for fluences above 5 x 10 15 cm -2 the surface disorder level in the Al-sublattice reaches the random level. Implantation damage recovers fast for annealing in oxidizing atmosphere but even for the highest fluence we recover almost completely all the damage after annealing at 1300 o C, independently of the annealing environment (reducing or oxidizing). Annealing above 1000 o C promotes the formation of Eu 2 O 3 in the samples with higher concentration of Eu. The optical activation of the rare earth ions at room temperature was observed after annealing at 800 o C by photoluminescence and ionoluminescence. In Al 2 O 3 lattice the highest intensity line of the Eu 3+ ions corresponds to the forced electric dipole 5 D 0 → 7 F 2 transition that occurs ∼616 nm. For the MgO samples the Eu 3+ optical activation was also achieved after implantation with different fluences. Here, the lanthanide recombination is dominated by the magnetic dipole 5 D 0 → 7 F 1 transition near by 590 nm commonly observed for samples were Eu 3+ is placed in a high symmetry local site. The results clearly demonstrate the possibility to get Eu incorporated in optical active regular lattice sites in wide gap oxides.

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

    Science.gov (United States)

    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

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

    OpenAIRE

    Venditti, Paola; Pamplona Gras, Reinald; Ayala, Victoria; Rosa, R. de; Caldarone, G.; Di Meo, S.

    2006-01-01

    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 (T-3)- or thyroxine (T-4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most ex...

  7. Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats

    International Nuclear Information System (INIS)

    Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

    2013-01-01

    Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-α levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. (author)

  8. Palm H-FAME Production through Partially Hydrogenation using Nickel/Carbon Catalyst to Increase Oxidation Stability

    Directory of Open Access Journals (Sweden)

    Ramayeni Elsa

    2018-01-01

    Full Text Available One of the methods to improve the oxidation stability of palm biodiesel is through partially hydrogenation. The production using Nickel/Carbon catalyst to speed up the reaction rate. Product is called Palm H-FAME (Hydrogenated FAME. Partial hydrogenation breaks the unsaturated bond on FAME (Fatty Acid Methyl Ester, which is a key component of the determination of oxidative properties. Changes in FAME composition by partial hydrogenation are predicted to change the oxidation stability so it does not cause deposits that can damage the injection system of diesel engine, pump system, and storage tank. Partial hydrogenation is carried out under operating conditions of 120 °C and 6 bar with 100:1, 100:3, 100:5, 100:10 % wt catalyst in the stirred batch autoclave reactor. H-FAME synthesis with 100:5 % wt Ni/C catalyst can decrease the iodine number which is the empirical measure of the number of unsaturated bonds from 91.78 to 82.38 (g-I2/100 g with an increase of oxidation stability from 585 to 602 minutes.

  9. Wine and oxidative stress: up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans.

    Science.gov (United States)

    Covas, María Isabel; Gambert, Philippe; Fitó, Montserrat; de la Torre, Rafael

    2010-02-01

    Wine and alcohol consumption has been considered to be protective against coronary heart disease development, an oxidative stress associated disease. Wine contains polyphenols displaying antioxidant properties tested in in vitro and in vivo studies. Due to this, a general consensus exists, both among the general public and the scientific community, that wine, particularly red wine, is an antioxidant beverage. Alcohol consumption, however, is associated with oxidative damage. Several studies have been carried out on the antioxidant health benefits of wine and wine polyphenols. However, adequate scientific evidence (Level I or II) is required to be provided before recommendations or statements which can reach the general public can be formulated. Here, we summarize the state of the art of the up-to-date body of knowledge, and the extent to which there exists evidence of the benefits of moderate wine consumption on oxidative damage in humans. From the available data, there is no evidence, at present, that sustained wine consumption provides antioxidant benefits in healthy volunteers other than to counteract a possible pro-oxidative effect of the alcohol. On the contrary, data on the antioxidant protective effect of red wine in oxidative stress situations are promising. In this way, the postprandial oxidative stress after a meal, despite the diversity of biomarkers used for its evaluation, is counteracted by the ingestion of wine. Further studies are warranted. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  10. Vitamin-E reduces the oxidative damage on delta-aminolevulinic dehydratase induced by lead intoxication in rat erythrocytes.

    Science.gov (United States)

    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.

  11. Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

    DEFF Research Database (Denmark)

    Lundby, Carsten; Pilegaard, Henriette; van Hall, Gerrit

    2003-01-01

    Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming...

  12. [Damage effects of chronic hypoxia on medulla oblongata associated with oxidative stress and cell apoptosis].

    Science.gov (United States)

    Hou, Xuefei; Ding, Yan; Nie, Zheng; Li, Hui; Tang, Yuhong; Zhou, Hua; Chen, Li; Zheng, Yu

    2012-08-01

    The aim of this study is to study the damage effects of chronic hypoxia on medulla oblongata and to explore whether the damage is associated with oxidative stress and cell apoptosis. Adult male SD rats were randomly divided into two groups: control group and chronic hypoxia group. Medulla oblongata was obtained for the following methods of analyses. Nissl's staining was used to examine the Niss bodies of neurons in medullary respiratory related nuclei, biochemistry methods were utilized to examine oxidant stress damage induced by chronic hypoxia on medulla oblongata through measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and RT-PCR technique was used to study the influence of apoptosis induced by chronic hypoxia on medulla oblongata through analyzing the levels of Bax mRNA and Bcl-2 mRNA. The results showed the optical densities of Nissl's staining in pre-BötC, NA, NTS, FN, and 12N were significantly decreased in chronic hypoxia group in comparison with that in control group (P 0.05). Bax mRNA expression had no obvious change and Bcl-2 mRNA expression significantly decreased in chronic hypoxia group in comparison with that in control group (P < 0.05). The results suggest that chronic hypoxia could bring about serious damage to medullary respiratory centers through aggravating oxidative stress and increasing cell apoptosis.

  13. Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients.

    Directory of Open Access Journals (Sweden)

    Serena Guidotti

    Full Text Available Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA, but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy.In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763 were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS production (2',7'-dichlorofluorescin diacetate staining. Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21, flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining.In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10.In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via

  14. Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients.

    Science.gov (United States)

    Guidotti, Serena; Minguzzi, Manuela; Platano, Daniela; Cattini, Luca; Trisolino, Giovanni; Mariani, Erminia; Borzì, Rosa Maria

    2015-01-01

    Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA), but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy. In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763) were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS) production (2',7'-dichlorofluorescin diacetate staining). Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21), flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining. In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10. In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via induction of

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

    Science.gov (United States)

    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.

  16. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    Directory of Open Access Journals (Sweden)

    Ye Han

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer and analyzed by high performance liquid chromatography (HPLC and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days drastically prevented the elevated activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP and triglyceride (TG in serum and the levels of malondialdehyde (MDA, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β in liver tissue (p < 0.05. Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05. Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

  17. Lipid oxidation. Part 2. Oxidation products of olive oil methyl esters.

    Science.gov (United States)

    Pokorný, J; Tài, P; Parízková, H; Smidrkalová, E; El-Tarras, M F; Janícek, G

    1976-01-01

    Olive oil was converted into methyl esters which were autoxidized at 60 degrees C. The composition of oxidized products was determined by the comparison of infrared spectra and NMR spectra of the original and acetylated samples, the sample reduced with potassium iodide and the acetylated reduced sample. Oxidized products were separated by preparative thin layer chromatography on silica gel and characterized by selective detection and by infrared spectrometry of the fractions. The oxidation products consisted of hydroperoxido butyl oleate, substituted hydroperoxides, mono- and disubstituted monomeric derivatives and a small amount of oligomers.

  18. Over-expression of heme oxygenase-1 promotes oxidative mitochondrial damage in rat astroglia.

    Science.gov (United States)

    Song, Wei; Su, Haixiang; Song, Sisi; Paudel, Hemant K; Schipper, Hyman M

    2006-03-01

    Glial heme oxygenase-1 is over-expressed in the CNS of subjects with Alzheimer disease (AD), Parkinson disease (PD) and multiple sclerosis (MS). Up-regulation of HO-1 in rat astroglia has been shown to facilitate iron sequestration by the mitochondrial compartment. To determine whether HO-1 induction promotes mitochondrial oxidative stress, assays for 8-epiPGF(2alpha) (ELISA), protein carbonyls (ELISA) and 8-OHdG (HPLC-EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole-cell compartments derived from cultured rat astroglia engineered to over-express human (h) HO-1 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [3H] thymidine incorporation and total cell counts. In rat astrocytes, hHO-1 over-expression (x 3 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 microM tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up-regulation of HO-1 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme-derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO-1 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. Copyright 2005 Wiley-Liss, Inc.

  19. Production of oceanic nitrous oxide by ammonia-oxidizing archaea

    Directory of Open Access Journals (Sweden)

    C. R. Löscher

    2012-07-01

    Full Text Available The recent finding that microbial ammonia oxidation in the ocean is performed by archaea to a greater extent than by bacteria has drastically changed the view on oceanic nitrification. The numerical dominance of archaeal ammonia-oxidizers (AOA over their bacterial counterparts (AOB in large parts of the ocean leads to the hypothesis that AOA rather than AOB could be the key organisms for the oceanic production of the strong greenhouse gas nitrous oxide (N2O that occurs as a by-product of nitrification. Very recently, enrichment cultures of marine ammonia-oxidizing archaea have been reported to produce N2O.

    Here, we demonstrate that archaeal ammonia monooxygenase genes (amoA were detectable throughout the water column of the eastern tropical North Atlantic (ETNA and eastern tropical South Pacific (ETSP Oceans. Particularly in the ETNA, comparable patterns of abundance and expression of archaeal amoA genes and N2O co-occurred in the oxygen minimum, whereas the abundances of bacterial amoA genes were negligible. Moreover, selective inhibition of archaea in seawater incubations from the ETNA decreased the N2O production significantly. In studies with the only cultivated marine archaeal ammonia-oxidizer Nitrosopumilus maritimus SCM1, we provide the first direct evidence for N2O production in a pure culture of AOA, excluding the involvement of other microorganisms as possibly present in enrichments. N. maritimus showed high N2O production rates under low oxygen concentrations comparable to concentrations existing in the oxycline of the ETNA, whereas the N2O production from two AOB cultures was comparably low under similar conditions. Based on our findings, we hypothesize that the production of N2O in tropical ocean areas results mainly from archaeal nitrification and will be affected by the predicted decrease in dissolved

  20. Association between Urinary Excretion of Cortisol and Markers of Oxidatively Damaged DNA and RNA in Humans

    DEFF Research Database (Denmark)

    Joergensen, Anders; Broedbaek, Kasper; Weimann, Allan

    2011-01-01

    Chronic psychological stress is associated with accelerated aging, but the underlying biological mechanisms are not known. Prolonged elevations of the stress hormone cortisol is suspected to play a critical role. Through its actions, cortisol may potentially induce oxidatively generated damage...... to cellular constituents such as DNA and RNA, a phenomenon which has been implicated in aging processes. We investigated the relationship between 24 h excretion of urinary cortisol and markers of oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine......, in a sample of 220 elderly men and women (age 65 - 83 years). We found a robust association between the excretion of cortisol and the oxidation markers (R(2)¿=¿0.15, P...

  1. Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage

    Science.gov (United States)

    Klungland, Arne; Rosewell, Ian; Hollenbach, Stephan; Larsen, Elisabeth; Daly, Graham; Epe, Bernd; Seeberg, Erling; Lindahl, Tomas; Barnes, Deborah E.

    1999-01-01

    DNA damage generated by oxidant byproducts of cellular metabolism has been proposed as a key factor in cancer and aging. Oxygen free radicals cause predominantly base damage in DNA, and the most frequent mutagenic base lesion is 7,8-dihydro-8-oxoguanine (8-oxoG). This altered base can pair with A as well as C residues, leading to a greatly increased frequency of spontaneous G·C→T·A transversion mutations in repair-deficient bacterial and yeast cells. Eukaryotic cells use a specific DNA glycosylase, the product of the OGG1 gene, to excise 8-oxoG from DNA. To assess the role of the mammalian enzyme in repair of DNA damage and prevention of carcinogenesis, we have generated homozygous ogg1−/− null mice. These animals are viable but accumulate abnormal levels of 8-oxoG in their genomes. Despite this increase in potentially miscoding DNA lesions, OGG1-deficient mice exhibit only a moderately, but significantly, elevated spontaneous mutation rate in nonproliferative tissues, do not develop malignancies, and show no marked pathological changes. Extracts of ogg1 null mouse tissues cannot excise the damaged base, but there is significant slow removal in vivo from proliferating cells. These findings suggest that in the absence of the DNA glycosylase, and in apparent contrast to bacterial and yeast cells, an alternative repair pathway functions to minimize the effects of an increased load of 8-oxoG in the genome and maintain a low endogenous mutation frequency. PMID:10557315

  2. Nitrous Oxide Production by Abundant Benthic Macrofauna

    DEFF Research Database (Denmark)

    Stief, Peter; Schramm, Andreas

    of the short-term metabolic induction of gut denitrification is the preferential production of nitrous oxide rather than dinitrogen. On a large scale, gut denitrification in, for instance, Chironomus plumosus larvae can increase the overall nitrous oxide emission of lake sediment by a factor of eight. We...... screened more than 20 macrofauna species for nitrous oxide production and identified filter-feeders and deposit-feeders that occur ubiquitously and at high abundance (e.g., chironomids, ephemeropterans, snails, and mussels) as the most important emitters of nitrous oxide. In contrast, predatory species...... that do not ingest large quantities of microorganisms produced insignificant amounts of nitrous oxide. Ephemera danica, a very abundant mayfly larva, was monitored monthly in a nitrate-polluted stream. Nitrous oxide production by this filter-feeder was highly dependent on nitrate availability...

  3. 4β-Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells.

    Science.gov (United States)

    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.

  4. OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells

    Science.gov (United States)

    Liu, Zhong-Jie; Zhao, Wei; Zhang, Qing-Guo; Li, Le; Lai, Lu-Ying; Jiang, Shan; Xu, Shi-Yuan

    2015-01-01

    Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use. PMID:26161242

  5. OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells

    Directory of Open Access Journals (Sweden)

    Zhong-Jie Liu

    2015-01-01

    Full Text Available Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1 which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS. SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use.

  6. The results of the lipids peroxidation products on the DNA bases as biological markers of the oxidative stress; Les adduits des produits de la peroxydation lipidique sur les bases de l'ADN comme biomarqueurs du stress oxydant

    Energy Technology Data Exchange (ETDEWEB)

    Falletti, O

    2007-10-15

    Different ways of DNA damages have been studied, among these ones the direct way of DNA damages formation by the reactive oxygen species (R.O.S.). This way leads to the formation of oxidative DNA damages. In 1990, works have suggested an indirect way of DNA damages formation, the lipids peroxidation. Instead of oxidizing directly DNA, the R.O.S. oxide the lipids present in the cells and their membranes; The products coming from this degradation are able to provoke DNA damages. This way has not been studied very much. The work of this thesis is axed on this DNA theme and lipids peroxidation. In the first chapter, we begin by presenting DNA and the direct way of oxidative damages formation by the R.O.S.Then, we speak about the cell lipids suffering oxidation reactions and the different ways of lipids oxidation. Then, we present how the lipid peroxidation is a source of damages for DNA. (N.C.)

  7. Oxidative stress generated damage to DNA by gastrointestinal exposure to insoluble particles

    DEFF Research Database (Denmark)

    Møller, Peter; Folkmann, J K; Danielsen, P H

    2012-01-01

    that gastrointestinal exposure to single-walled carbon nanotubes (SWCNT), fullerenes C60, carbon black, titanium dioxide and diesel exhaust particles generates oxidized DNA base lesions in organs such as the bone marrow, liver and lung. Oral exposure to nanosized carbon black has also been associated with increased...... level of lipid peroxidation derived exocyclic DNA adducts in the liver, suggesting multiple pathways of oxidative stress for particle-generated damage to DNA. At equal dose, diesel exhaust particles (SRM2975) generated larger levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in rat liver than carbon black...

  8. Role of oxidative DNA damage in genome instability and cancer

    International Nuclear Information System (INIS)

    Bignami, M.; Kunkel, T.

    2009-01-01

    Inactivation of mismatch repair (MMR) is associated with a dramatic genomic instability that is observed experimentally as a mutator phenotype and micro satellite instability (MSI). It has been implicit that the massive genetic instability in MMR defective cells simply reflects the accumulation of spontaneous DNA polymerase errors during DNA replication. We recently identified oxidation damage, a common threat to DNA integrity to which purines are very susceptible, as an important cofactor in this genetic instability

  9. Levels of oxidative damage and lipid peroxidation in thyroid neoplasia.

    LENUS (Irish Health Repository)

    Young, Orla

    2012-02-01

    BACKGROUND: This study assessed the presence of oxidative damage and lipid peroxidation in thyroid neoplasia. METHODS: Using tissue microarrays and immunohistochemistry, we assessed levels of DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in 71 follicular thyroid adenoma (FTA), 45 papillary thyroid carcinoma (PTC), and 17 follicular thyroid carcinoma (FTC) and matched normal thyroid tissue. RESULTS: Cytoplasmic 8-oxo-dG and 4-HNE expression was significantly higher in FTA, FTC, and PTC tissue compared to matched normal tissue (all p values < .001). Similarly, elevated nuclear levels of 8-oxo-dG were seen in all in FTA, FTC, and PTC tissue compared to matched normal (p values < .07, < .001, < .001, respectively). In contrast, a higher level of 4-HNE expression was detected in normal thyroid tissue compared with matched tumor tissue (p < .001 for all groups). Comparing all 3 groups, 4-HNE levels were higher than 8-oxo-dG levels (p < .001 for all groups) except that cytoplasmic levels of 8-oxo-dG were higher than 4-HNE in all (p < .001). These results were independent of proliferation status. CONCLUSION: High levels of DNA damage and lipid peroxidation in benign and malignant thyroid neoplasia indicates this damage is an early event that may influence disease progression.

  10. Damage analysis. Product improvement through damage analysis; Schadensanalyse. Produktverbesserung durch Schadensanalyse

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    Within the 37th VDI annual meeting from 19th to 20th May, 2011 in Wuerzburg (Federal Republic of Germany) the following lectures and posters were presented: (1) Malpractice of material processing and heat processing of large gear wheels (P. Sommer); (2) Damages by faulty heat treatment - Case studies: Glow testing at a heat exchanger and wheel breakage of a high-strength screw connection (A. Thomas); (3) Crack formation in pole end plates of high-performance generators of a pumped-storage power plant - Causes and possibilities of remedy (J. Kinder); (4) Grind burn inspection for damage prevention at wind turbine gearboxes - Use of different processes for the investigation of peripheral-zone properties of case-hardened components (T. Griggel); (5) Damage inspection in coal mines using products from the degradation process as an example - damage - inspection - solution: This is the working method of the certification body (C. Kleine-Hegermann); (6) Damages at the sealing rings - Causes of the failure at radial shaft rings (K. Marchetti); (7) Thermal analyses at faulty plastic components (O. Jacobs); (8) Application of the micro computer tomography at damages of fibre-reinforced materials (H. Dinnebier); (9) The significance of 'material defects' from the view of lay people, lawyers and engineers - 'Material defect' in the literature, set of rules and expert opinion (C. Klinger); (10) Material defects from a legal view (P. Henseler); (11) Significance of material defects from the view of an engineering insurer (C. Harden); (12) Wear analyses by means of RNT and non-destructive surface analytics (K. Poehlmann); (13) Damages by means of non-metallic inclusions using ICE 3 as an example - Significance and localisation of single non-metallic inclusions in large components (D. Bettge); (14) Cathodic corrosion protection of pipeline steels (H.-G. Schoeneich); (15) Non-destructive and destructive investigations when assessing damages of corrosion at a

  11. Effects of prior surface damage on high-temperature oxidation of Fe-, Ni-, and Co-based alloys

    Energy Technology Data Exchange (ETDEWEB)

    Blau, Peter Julian [ORNL; Lowe, Tracie M [ORNL; Pint, Bruce A [ORNL

    2009-01-01

    Multi-component metallic alloys have been developed to withstand high-temperature service in corrosive environments. Some of these applications, like exhaust valve seats in internal combustion engines, must also resist sliding, impact, and abrasion. The conjoint effects of temperature, oxidation, and mechanical contact can result in accelerated wear and the formation of complex surface layers whose properties differ from those of the base metal and the oxide scale that forms in the absence of mechanical contact. The authors have investigated the effects of prior surface damage, produced by scratch tests, on the localized reformation of oxide layers. Three high-performance commercial alloys, based on iron, nickel, and cobalt, were used as model materials. Thermogravimetric analysis (TGA) was used to determine their static oxidation rates at elevated temperature (850o C). A micro-abrasion, ball-cratering technique was used to measure oxide layer thickness and to compare it with TGA results. By using taper-sectioning techniques and energy-dispersive elemental mapping, a comparison was made between oxide compositions grown on non-damaged surfaces and oxides that formed on grooves produced by a diamond stylus. Microindentation and scratch hardness data revealed the effects of high temperature exposure on both the substrate hardness and the nature of oxide scale disruption. There were significant differences in elemental distribution between statically-formed oxides and those that formed on scratched regions

  12. Modeling of nitrous oxide production by autotrophic ammonia-oxidizing bacteria with multiple production pathways.

    Science.gov (United States)

    Ni, Bing-Jie; Peng, Lai; Law, Yingyu; Guo, Jianhua; Yuan, Zhiguo

    2014-04-01

    Autotrophic ammonia oxidizing bacteria (AOB) have been recognized as a major contributor to N2O production in wastewater treatment systems. However, so far N2O models have been proposed based on a single N2O production pathway by AOB, and there is still a lack of effective approach for the integration of these models. In this work, an integrated mathematical model that considers multiple production pathways is developed to describe N2O production by AOB. The pathways considered include the nitrifier denitrification pathway (N2O as the final product of AOB denitrification with NO2(-) as the terminal electron acceptor) and the hydroxylamine (NH2OH) pathway (N2O as a byproduct of incomplete oxidation of NH2OH to NO2(-)). In this model, the oxidation and reduction processes are modeled separately, with intracellular electron carriers introduced to link the two types of processes. The model is calibrated and validated using experimental data obtained with two independent nitrifying cultures. The model satisfactorily describes the N2O data from both systems. The model also predicts shifts of the dominating pathway at various dissolved oxygen (DO) and nitrite levels, consistent with previous hypotheses. This unified model is expected to enhance our ability to predict N2O production by AOB in wastewater treatment systems under varying operational conditions.

  13. LYCOPENE EFFICIENCY IN THE MODULATION OF OXIDATIVE DAMAGE IN DIFFERENT TISSUES OF GAMMA IRRADIATED RATS

    International Nuclear Information System (INIS)

    EL-TAHAWY, N.A.; NADA, A.S.; REZK, R.G.

    2008-01-01

    Exposure to ionizing radiation induces oxidative stress that has been recognized as an important etiological factor in the causation of several chronic diseases. Lycopene, a carotenoid almost exclusively present in tomatoes and tomatoes products, is a lipid soluble antioxidant claimed to possess cardio protective and anticancer properties. The present study was designed to determine the possible modulator effects of lycopene on radiation-induced oxidative damage to liver, spleen and lung tissues. Animals were supplemented with lycopene (5 mg/kg body weight/ day) by gavages for two weeks before whole body exposure to gamma rays and within the period of irradiation (3 successive doses, each of 3 Gy at 72 hours intervals). Animals were sacrificed on the 3 r d day post the last irradiation session.The results obtained in the present study showed that whole body gamma irradiation produced oxidative stress manifested by significant elevation in lipid peroxides levels measured as thiobarbituric acid reactive substances (TBARS) associated with significant decrease of nitric oxide (NO) content. Non-significant change in total cupper (Cu) in the three tissues was recorded while significant increase of total iron (Fe) was observed in liver and spleen tissues only. Liver tissue of irradiated rats showed significant decrease in the activities of the antioxidant enzymes as superoxide dismutase (SOD) and catalase (CAT). In spleen tissues, there was a significant increase of SOD and significant decrease of CAT activities while in lung tissues, both SOD and CAT activities showed significant increase.Histological observations of photomicrograph of liver sections showed that radiation-induced sever damage obvious by dilated portal vein, ruptured hepatocytes, necrotic, pyknotic, karyolitic nuclei and vacuolated cytoplasm. In spleen tissue, radiation was induced degeneration of lymphatic nodules, dilation follicular artery and marked hemorrhage. In lung tissue, radiation- induces ill

  14. Frequency of polymorphism -262 c/t in catalase gene and oxidative damage in Slovak children with bronchial asthma.

    Science.gov (United States)

    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.

  15. Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

    Directory of Open Access Journals (Sweden)

    Vučeljić Marina

    2006-01-01

    Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

  16. Echinacoside Induces Apoptosis in Human SW480 Colorectal Cancer Cells by Induction of Oxidative DNA Damages

    Directory of Open Access Journals (Sweden)

    Liwei Dong

    2015-06-01

    Full Text Available Echinacoside is a natural compound with potent reactive oxygen species (ROS-scavenging and anti-oxidative bioactivities, which protect cells from oxidative damages. As cancer cells are often under intense oxidative stress, we therefore tested if Echinacoside treatment would promote cancer development. Surprisingly, we found that Echinacoside significantly inhibited the growth and proliferation of a panel of cancer cell lines. Treatment of the human SW480 cancer cells with Echinacoside resulted in marked apoptosis and cell cycle arrest, together with a significant increase in active caspase 3 and cleaved PARP, and upregulation of the G1/S-CDK blocker CDKN1B (p21. Interestingly, immunocytochemistry examination of drug-treated cancer cells revealed that Echinacoside caused a significant increase of intracellular oxidized guanine, 8-oxoG, and dramatic upregulation of the double-strand DNA break (DSB-binding protein 53BP1, suggesting that Echinacoside induced cell cycle arrest and apoptosis in SW480 cancer cells via induction of oxidative DNA damages. These results establish Echinacoside as a novel chemical scaffold for development of anticancer drugs.

  17. Protection against oxidative damage in human erythrocytes and preliminary photosafety assessment of Punica granatum seed oil nanoemulsions entrapping polyphenol-rich ethyl acetate fraction.

    Science.gov (United States)

    Baccarin, Thaisa; Mitjans, Montserrat; Lemos-Senna, Elenara; Vinardell, Maria Pilar

    2015-12-25

    The main purpose of the present study is to evaluate the ability of nanoemulsion entrapping pomegranate peel polyphenol-rich ethyl acetate fraction (EAF) prepared from pomegranate seed oil and medium chain triglyceride to protect human erythrocyte membrane from oxidative damage and to assess preliminary in vitro photosafety. In order to evaluate the phototoxic effect of nanoemulsions, human red blood cells (RBCs) are used as a biological model and the rate of haemolysis and photohaemolysis (5 J cm(-2) UVA) is assessed in vitro. The level of protection against oxidative damage caused by the peroxyl radical generator AAPH in human RBCs as well as its effects on bilayer membrane characteristics such as fluidity, protein profile and RBCs morphology are determined. EAF-loaded nanoemulsions do not promote haemolysis or photohaemolysis. Anisotropy measurements show that nanoemulsions significantly retrain the increase in membrane fluidity caused by AAPH. SDS-PAGE analysis reveals that AAPH induced degradation of membrane proteins, but that nanoemulsions reduce the extension of degradation. Scanning electron microscopy examinations corroborate the interaction between AAPH, nanoemulsions and the RBC membrane bilayer. Our work demonstrates that Punica granatum nanoemulsions are photosafe and protect RBCs against oxidative damage and possible disturbance of the lipid bilayer of biomembranes. Moreover it suggests that these nanoemulsions could be promising new topical products to reduce the effects of sunlight on skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Evaluation of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage

    Directory of Open Access Journals (Sweden)

    R Sunil Kumar

    2017-01-01

    Full Text Available Objective: The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. Materials and Methods: The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. Results: The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. Conclusion: C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy.

  19. Mineralogical and chemical assessment of concrete damaged by the oxidation of sulfide-bearing aggregates: Importance of thaumasite formation on reaction mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, A. [Centre de Recherche sur les Infrastructures en Beton (CRIB), Universite Laval, 1065 ave de la Medecine, Quebec, QC, Canada G1V 0A6 (Canada); Duchesne, J., E-mail: josee.duchesne@ggl.ulaval.ca [Centre de Recherche sur les Infrastructures en Beton (CRIB), Universite Laval, 1065 ave de la Medecine, Quebec, QC, Canada G1V 0A6 (Canada); Fournier, B. [Centre de Recherche sur les Infrastructures en Beton (CRIB), Universite Laval, 1065 ave de la Medecine, Quebec, QC, Canada G1V 0A6 (Canada); Durand, B. [Institut de recherche d' Hydro-Quebec (IREQ), 1740 boul. Lionel-Boulet, Varennes, QC, Canada J3X 1S1 (Canada); Rivard, P. [Universite de Sherbrooke, Sherbrooke, QC, Canada J1K 2R1 (Canada); Shehata, M. [Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada)

    2012-10-15

    Damages in concrete containing sulfide-bearing aggregates were recently observed in the Trois-Rivieres area (Quebec, Canada), characterized by rapid deterioration within 3 to 5 years after construction. A petrographic examination of concrete core samples was carried out using a combination of tools including: stereomicroscopic evaluation, polarized light microscopy, scanning electron microscopy, X-ray diffraction and electron microprobe analysis. The aggregate used to produce concrete was an intrusive igneous rock with different metamorphism degrees and various proportions of sulfide minerals. In the rock, sulfide minerals were often surrounded by a thin layer of carbonate minerals (siderite). Secondary reaction products observed in the damaged concrete include 'rust' mineral forms (e.g. ferric oxyhydroxides such as goethite, limonite (FeO (OH) nH{sub 2}O) and ferrihydrite), gypsum, ettringite and thaumasite. In the presence of water and oxygen, pyrrhotite oxidizes to form iron oxyhydroxides and sulphuric acid. The acid then reacts with the phases of the cement paste/aggregate and provokes the formation of sulfate minerals. Understanding both mechanisms, oxidation and internal sulfate attack, is important to be able to duplicate the damaging reaction in laboratory conditions, thus allowing the development of a performance test for evaluating the potential for deleterious expansion in concrete associated with sulfide-bearing aggregates.

  20. Mineralogical and chemical assessment of concrete damaged by the oxidation of sulfide-bearing aggregates: Importance of thaumasite formation on reaction mechanisms

    International Nuclear Information System (INIS)

    Rodrigues, A.; Duchesne, J.; Fournier, B.; Durand, B.; Rivard, P.; Shehata, M.

    2012-01-01

    Damages in concrete containing sulfide-bearing aggregates were recently observed in the Trois-Rivières area (Quebec, Canada), characterized by rapid deterioration within 3 to 5 years after construction. A petrographic examination of concrete core samples was carried out using a combination of tools including: stereomicroscopic evaluation, polarized light microscopy, scanning electron microscopy, X-ray diffraction and electron microprobe analysis. The aggregate used to produce concrete was an intrusive igneous rock with different metamorphism degrees and various proportions of sulfide minerals. In the rock, sulfide minerals were often surrounded by a thin layer of carbonate minerals (siderite). Secondary reaction products observed in the damaged concrete include “rust” mineral forms (e.g. ferric oxyhydroxides such as goethite, limonite (FeO (OH) nH 2 O) and ferrihydrite), gypsum, ettringite and thaumasite. In the presence of water and oxygen, pyrrhotite oxidizes to form iron oxyhydroxides and sulphuric acid. The acid then reacts with the phases of the cement paste/aggregate and provokes the formation of sulfate minerals. Understanding both mechanisms, oxidation and internal sulfate attack, is important to be able to duplicate the damaging reaction in laboratory conditions, thus allowing the development of a performance test for evaluating the potential for deleterious expansion in concrete associated with sulfide-bearing aggregates.

  1. Oxidative Damage and Its Possible Mechanism

    Directory of Open Access Journals (Sweden)

    Tingting Wang

    2016-06-01

    Full Text Available Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNAdamage, 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 (pyrogallolautoxidation, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays.Results: Fisetin increased dose-dependently its protective percentages against •OH-inducedDNA damage (IC50 value =1535.00±29.60 μM. It also increased its radical-scavengingpercentages 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±0.14μM, and 1.49±0.16 μM, respectively.Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damagepossibly via reactive oxygen species (ROS scavenging approach, which is assumed to behydrogen atom (H• and/or single electron (e donation (HAT/SET pathways. In the HATpathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an importantrole, because it can be ultimately oxidized to a stable ortho-benzoquinone form.

  2. Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

    Directory of Open Access Journals (Sweden)

    Casper G. Schalkwijk

    2013-07-01

    Full Text Available Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE Nε-(1-carboxymethyllysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.

  3. Base excision repair of oxidative DNA damage and association with cancer and aging

    DEFF Research Database (Denmark)

    Maynard, Scott; Schurman, Shepherd H; Harboe, Charlotte

    2009-01-01

    Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack DNA...

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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 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 + 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Lili, E-mail: llxin@suda.edu.cn [School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu (China); Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123 (China); Wang, Jianshu [Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou, Jiangsu (China); Zhang, Leshuai W. [School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 215123 (China); Che, Bizhong; Dong, Guangzhu [School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu (China); Fan, Guoqiang; Cheng, Kaiming [Suzhou Industrial Park Centers for Disease Control and Prevention, 58 Suqian Road, Suzhou, Jiangsu (China)

    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{sup +} 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 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

  6. Production and beam annealing of damage in carbon implanted silicon

    International Nuclear Information System (INIS)

    Kool, W.H.; Roosendaal, H.E.; Wiggers, L.W.; Saris, F.W.

    1978-01-01

    The annealing of damage introduced by 70 keV C implantation of Si is studied for impact of H + and He + beams in the energy interval 30 to 200 keV. For a good description of the annealing behaviour it is necessary to account for the damage introduction which occurs simultaneously. It turns out that the initial damage annealing rate is proportional to the amount of damage. The proportionality constant is related to a quantity introduced in an earlier paper in order to describe saturation effects in the damage production after H + or He + impact in unimplanted Si. This indicates that the same mechanism governs both processes: beam induced damage annealing and saturation of the damage introduction. (author)

  7. Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

    Directory of Open Access Journals (Sweden)

    Geoffrey R Bennett

    Full Text Available Host base excision repair (BER proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1 and mutY homolog (MYH as well as DNA polymerase beta (Polβ. While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

  8. Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead

    International Nuclear Information System (INIS)

    Stacchiotti, Alessandra; Morandini, Fausta; Bettoni, Francesca; Schena, Ilaria; Lavazza, Antonio; Grigolato, Pier Giovanni; Apostoli, Pietro; Rezzani, Rita; Aleo, Maria Francesca

    2009-01-01

    A close link between stress protein up-regulation and oxidative damage may provide a novel therapeutic tool to counteract nephrotoxicity induced by toxic metals in the human population, mainly in children, of industrialized countries. Here we analysed the time course of the expression of several heat shock proteins, glucose-regulated proteins and metallothioneins in a rat proximal tubular cell line (NRK-52E) exposed to subcytotoxic doses of inorganic mercury and lead. Concomitantly, we used morphological and biochemical methods to evaluate metal-induced cytotoxicity and oxidative damage. In particular, as biochemical indicators of oxidative stress we detected reactive oxygen species (ROS) and nitrogen species (RNS), total glutathione (GSH) and glutathione-S-transferase (GST) activity. Our results clearly demonstrated that mercury increases ROS and RNS levels and the expressions of Hsp25 and inducible Hsp72. These findings are corroborated by evident mitochondrial damage, apoptosis or necrosis. By contrast, lead is unable to up-regulate Hsp72 but enhances Grp78 and activates nuclear Hsp25 translocation. Furthermore, lead causes endoplasmic reticulum (ER) stress, vacuolation and nucleolar segregation. Lastly, both metals stimulate the over-expression of MTs, but with a different time course. In conclusion, in NRK-52E cell line the stress response is an early and metal-induced event that correlates well with the direct oxidative damage induced by mercury. Indeed, different chaperones are involved in the specific nephrotoxic mechanism of these environmental pollutants and work together for cell survival.

  9. Transparent conducting oxides and production thereof

    Science.gov (United States)

    Gessert, Timothy A.; Yoshida, Yuki; Coutts, Timothy J.

    2014-06-10

    Transparent conducting oxides and production thereof are disclosed. An exemplary method of producing a transparent conducting oxide (TCO) material may comprise: providing a TCO target doped with either a high-permittivity oxide or a low-permittivity oxide in a process chamber. The method may also comprise depositing a metal oxide on the target in the process chamber to form a thin film having enhanced optical properties without substantially decreasing electrical quality.

  10. Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A. B; Desler, Claus; Martin-Bertelsen, Tomas

    2013-01-01

    therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods To separate the changes induced by bacteria from those of the inflammatory cells...... intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell...... cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome...

  11. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  12. Oxidative stress damage as a detrimental factor in preterm birth pathology.

    Science.gov (United States)

    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.

  13. Ballet dancers cardiorespiratory, oxidative and muscle damage responses to classes and rehearsals.

    Science.gov (United States)

    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 Ballet dancers' muscle damage and oxidative stress responses seem not to be dependent on exercise intensity based on VO2 responses.

  14. Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids

    DEFF Research Database (Denmark)

    Cadet, Jean; Loft, Steffen; Olinski, Ryszard

    2012-01-01

    A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to nucleic acids. Perhaps as a consequence of this breadth of research expertise, there are nomenclature problems for several of the ...

  15. Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

    Directory of Open Access Journals (Sweden)

    José J. Gaforio

    2011-10-01

    Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  16. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2012-01-01

    Full Text Available The unceasing need for oxygen is in contradiction to the fact that it is in fact toxic to mammals. Namely, its monovalent reduction can have as a consequence the production of short-living, chemically very active free radicals and certain non-radical agents (nitrogen-oxide, superoxide-anion-radicals, hydroxyl radicals, peroxyl radicals, singlet oxygen, peroxynitrite, hydrogen peroxide, hypochlorous acid, and others. There is no doubt that they have numerous positive roles, but when their production is stepped up to such an extent that the organism cannot eliminate them with its antioxidants (superoxide-dismutase, glutathione-peroxidase, catalase, transferrin, ceruloplasmin, reduced glutathion, and others, a series of disorders is developed that are jointly called „oxidative stress.“ The reactive oxygen species which characterize oxidative stress are capable of attacking all main classes of biological macromolecules, actually proteins, DNA and RNA molecules, and in particular lipids. The free radicals influence lipid peroxidation in cellular membranes, oxidative damage to DNA and RNA molecules, the development of genetic mutations, fragmentation, and the altered function of various protein molecules. All of this results in the following consequences: disrupted permeability of cellular membranes, disrupted cellular signalization and ion homeostasis, reduced or loss of function of damaged proteins, and similar. That is why the free radicals that are released during oxidative stress are considered pathogenic agents of numerous diseases and ageing. The type of damage that will occur, and when it will take place, depends on the nature of the free radicals, their site of action and their source. [Projekat Ministarstva nauke Republike Srbije, br. 173034, br. 175061 i br. 31085

  17. Structural and electrical characterization of HBr/O2 plasma damage to Si substrate

    International Nuclear Information System (INIS)

    Fukasawa, Masanaga; Nakakubo, Yoshinori; Matsuda, Asahiko; Takao, Yoshinori; Eriguchi, Koji; Ono, Kouichi; Minami, Masaki; Uesawa, Fumikatsu; Tatsumi, Tetsuya

    2011-01-01

    Silicon substrate damage caused by HBr/O 2 plasma exposure was investigated by spectroscopic ellipsometry (SE), high-resolution Rutherford backscattering spectroscopy, and transmission electron microscopy. The damage caused by H 2 , Ar, and O 2 plasma exposure was also compared to clarify the ion-species dependence. Although the damage basically consists of a surface oxidized layer and underlying dislocated Si, the damage structure strongly depends on the incident ion species, ion energy, and oxidation during air and plasma exposure. In the case of HBr/O 2 plasma exposure, hydrogen generated the deep damaged layer (∼10 nm), whereas ion-enhanced diffusion of oxygen, supplied simultaneously by the plasma, caused the thick surface oxidation. In-line monitoring of damage thicknesses by SE, developed with an optimized optical model, showed that the SE can be used to precisely monitor damage thicknesses in mass production. Capacitance-voltage (C-V) characteristics of a damaged layer were studied before and after diluted-HF (DHF) treatment. Results showed that a positive charge is generated at the surface oxide-dislocated Si interface and/or in the bulk oxide after plasma exposure. After DHF treatment, most of the positive charges were removed, while the thickness of the ''Si recess'' was increased by removing the thick surface oxidized layer. As both the Si recess and remaining dislocated Si, including positive charges, cause the degradation of electrical performance, precise monitoring of the surface structure and understanding its effect on device performance is indispensable for creating advanced devices.

  18. Hypoxia-ischemia and retinal ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Charanjit Kaur

    2008-08-01

    Full Text Available Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF and nitric oxide synthase (NOS. Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina

  19. Age- and gender-related alteration in plasma advanced oxidation protein products (AOPP) and glycosaminoglycan (GAG) concentrations in physiological ageing.

    Science.gov (United States)

    Komosinska-Vassev, Katarzyna; Olczyk, Pawel; Winsz-Szczotka, Katarzyna; Kuznik-Trocha, Kornelia; Klimek, Katarzyna; Olczyk, Krystyna

    2012-02-13

    The authors studied the role of increased oxidative stress in the development of oxidative protein damage and extracellular matrix (ECM) components in ageing. The age- and gender-associated disturbances in connective tissue metabolism were evaluated by the plasma chondroitin sulphated glycosaminoglycans (CS-GAG) and non-sulphated GAG-hyaluronan (HA) measurements. Plasma concentration of advanced oxidation protein products (AOPP) was analysed in order to assess oxidative protein damage and evaluate the possible deleterious role of oxidative phenomenon on tissue proteoglycans' metabolism during the physiological ageing process. Sulphated and non-sulphated GAGs as well as AOPP were quantified in plasma samples from 177 healthy volunteers. A linear age-related decline of plasma CS-GAG level was found in this study (r=-0.46; page (r=0.44; page-dependent relationship has been shown in regard to AOPP. AOPP levels significantly increased with age (r=0.63; pphysiological ageing. A significant correlation was found between the concentrations of AOPP and both CS-GAG (r=-0.31; page changes in the ECM are reflected by CS-GAG and HA plasma levels. Strong correlations between AOPP and ECM components indicate that oxidative stress targets protein and non-protein components of the connective tissue matrix during human ageing.

  20. Arsenite induced oxidative damage in mouse liver is associated with increased cytokeratin 18 expression

    Energy Technology Data Exchange (ETDEWEB)

    Gonsebatt, M.E. [UNAM, Ciudad Universitaria, Dept. Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Mexico (Mexico); Razo, L.M. del; Sanchez-Pena, L.C. [Seccion de Toxicologia, CINVESTAV, Mexico (Mexico); Cerbon, M.A. [Facultad de Quimica, UNAM, Departamento de Biologia, Mexico (Mexico); Zuniga, O.; Ramirez, P. [Facultad de Estudios Superiores Cuautitlan, UNAM, Laboratorio de Toxicologia Celular, Coordinacion General de Estudios de Posgrado e Investigacion, Cuautitlan Izcalli, Estado de Mexico (Mexico)

    2007-09-15

    Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously observed that sodium arsenite (SA) induced the synthesis of CK18 protein and promotes a dose-related disruption of cytoplasmic CK18 filaments in a human hepatic cell line. Both abnormal gene expression and disturbance of structural organization are toxic effects that are likely to cause liver disease by interfering with normal hepatocyte function. To investigate if a disruption in the CK18 expression pattern is associated with arsenite liver damage, we investigated CK18 mRNA and protein levels in liver slices treated with low levels of SA. Organotypic cultures were incubated with 0.01, 1 and 10 {mu}M of SA in the absence and presence of N-acetyl cysteine (NAC). Cell viability and inorganic arsenic metabolism were determined. Increased expression of CK18 was observed after exposure to SA. The addition of NAC impeded the oxidative effects of SA exposure, decreasing the production of thiobarbituric acid-reactive substances and significantly diminishing the up regulation of CK18 mRNA and protein. Liver arsenic levels correlated with increased levels of mRNA. Mice treated with intragastric single doses of 2.5 and 5 mg/kg of SA showed an increased expression of CK18. Results suggest that CK18 expression may be a sensible early biomarker of oxidative stress and damage induced by arsenite in vitro and in vivo. Then, during SA exposure, altered CK expression may compromise liver function. (orig.)

  1. Serum Advanced Oxidation Protein Products in Oral Squamous Cell Carcinoma: Possible Markers of Diagnostic Significance

    Directory of Open Access Journals (Sweden)

    Abhishek Singh Nayyar

    2013-07-01

    Full Text Available Background: The aim of this study was to measure the concentrations (levels ofserum total proteins and advanced oxidation protein products as markers of oxidantmediated protein damage in the sera of patients with oral cancers.Methods: The study consisted of the sera analyses of serum total protein andadvanced oxidation protein products’ levels in 30 age and sex matched controls, 60patients with reported pre-cancerous lesions and/or conditions and 60 patients withhistologically proven oral squamous cell carcinoma. One way analyses of variance wereused to test the difference between groups. To determine which of the two groups’ meanswere significantly different, the post-hoc test of Bonferroni was used. The results wereaveraged as mean ± standard deviation. In the above test, P values less than 0.05 weretaken to be statistically significant. The normality of data was checked before thestatistical analysis was performed.Results: The study revealed statistically significant variations in serum levels ofadvanced oxidation protein products (P<0.001. Serum levels of total protein showedextensive variations; therefore the results were largely inconclusive and statisticallyinsignificant.Conclusion: The results emphasize the need for more studies with larger samplesizes to be conducted before a conclusive role can be determined for sera levels of totalprotein and advanced oxidation protein products as markers both for diagnosticsignificance and the transition from the various oral pre-cancerous lesions and conditionsinto frank oral cancers.

  2. [Effect of germacrone in alleviating HUVECs damaged by H2O2-induced oxidative stress].

    Science.gov (United States)

    Chen, Qiong-Fang; Wang, Gang; Tang, Li-Qing; Yu, Xian-Wen; Li, Zhao-Fei; Yang, Xiu-Fen

    2017-09-01

    This study focuses on the protective effect of germacrone on human umbilical vein endothelial cells(HUVECs) damaged by H2O2-induced oxidative stress and its possible mechanisms. The oxidative damage model was established by using 500 μmol•L⁻¹ H2O2 to treat HUVECs for 3 hours, and then protected with different concentrations of germacrone for 24 hours. The effect of germacrone on cell viability of HUVECs damaged by H2O2 was detected by MTT. The contents of PGI2, TXB2, ET-1, t-PA, PAI-1, TNF-α and IL-6 were detected by ELISA. The content of NO was detected by using nitrate reductase method. Colorimetry was used to detect NOS and GSH-Px. The contents of MDA, SOD and LDH were detected by TBA, WST-1 and microplate respectively. Apoptosis was observed by Hoechst 33258 fluorescent staining. The mRNA expressions of Bax, Bcl-2 and Caspase-3 in cells were detected by RT-PCR. The results showed that the cell damage rate was 52% after treated with 500 μmol•L⁻¹ H2O2 for 3 hours. The cell activity was increasing with the rise of germacrone concentration within the range of 20-200 mol•L⁻¹. Compared with normal group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were lower after damaged with H2O2. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were increased. Compared with model group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were increased after treated with germacrone. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were lower after treated with germacrone. According to Hoechst 33258 fluorescence staining, compared with normal group, the cell membrane and the nucleus showed strong dense blue fluorescence, and the number of cells significantly decreased in model group. Compared with model group, blue fluorescence intensity decreased in drug group. The above findings demonstrate that

  3. Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic exercise.

    Science.gov (United States)

    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.

  4. Effects of environmental pollution on endogenous oxidative DNA damage in humans

    Czech Academy of Sciences Publication Activity Database

    Singh, R.; Kaur, B.; Kalina, I.; Popov, T. A.; Georgieva, T.; Garte, S.; Binková, Blanka; Šrám, Radim; Taioli, E.; Farmer, P. B.

    2007-01-01

    Roč. 620, - (2007), s. 71-82 ISSN 0027-5107 Grant - others:EU(NO) 2000 -00091; EU(NO) G0100873 Institutional research plan: CEZ:AV0Z50390512 Source of funding: R - rámcový projekt EK ; R - rámcový projekt EK Keywords : oxidative DNA damage * polycyclic aromatic hydrocarbons * -oxo-deoxyguanosine Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.159, year: 2007

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

    Science.gov (United States)

    Haworth, Kristina M; Chandler, Heather L

    2017-05-01

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

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

    Science.gov (United States)

    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.

  7. Systemic oxidatively generated DNA/RNA damage in clinical depression

    DEFF Research Database (Denmark)

    Jorgensen, Anders; Krogh, Jesper; Miskowiak, Kamilla

    2013-01-01

    oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, were determined in healthy controls (N=28), moderately depressed, non-medicated patients (N=26) and severely depressed patients eligible for electroconvulsive therapy...... for trend=0.004). The 8-oxoGuo excretion was further increased after clinically effective ECT compared with pre-ECT values (P=0.006). There were no differences in 8-oxodG excretion between the groups or pre- vs. post-ECT. LIMITATIONS: Small sample size and the inclusion of both unipolar and bipolar patients...

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

    Energy Technology Data Exchange (ETDEWEB)

    Ferramola, Mariana L.; Pérez Díaz, Matías F.F. [Department of Biochemistry and Biological Sciences, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, IMIBIO-SL, CONICET, San Luis (Argentina); Honoré, Stella M.; Sánchez, Sara S. [Department of Development Biology, INSIBIO, National University of Tucumán, CONICET-UNT, Tucumán (Argentina); Antón, Rosa I. [Department of Chemistry, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, INQUISAL, CONICET, San Luis (Argentina); Anzulovich, Ana C. [Department of Biochemistry and Biological Sciences, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, IMIBIO-SL, CONICET, San Luis (Argentina); Giménez, María S., E-mail: mgimenez@unsl.edu.ar [Department of Biochemistry and Biological Sciences, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, IMIBIO-SL, CONICET, San Luis (Argentina)

    2012-12-15

    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) tap 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

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

    International Nuclear Information System (INIS)

    Ferramola, Mariana L.; Pérez Díaz, Matías F.F.; Honoré, Stella M.; Sánchez, Sara S.; Antón, Rosa I.; Anzulovich, Ana C.; Giménez, María S.

    2012-01-01

    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 2+ ; and (3) and (6) tap water containing 100 ppm of Cd 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

  10. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise

    2015-01-01

    Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged...... 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency......, cholesterol and glycosylated hemoglobin (HbA1c). In the group of men, there were significant positive associations between alcohol intake, HbA1c and FPG-sensitive sites in multivariate analysis. The levels of metabolic risk factors were positively associated with age, yet only few subjects fulfilled all...

  11. Structural influences on the laser damage resistance of optical oxide coatings for use at 1064 nm

    Energy Technology Data Exchange (ETDEWEB)

    Hacker, E; Lauth, H; Meyer, J; Weissbrodt, P [Zeiss Jena GmbH, Jena (Germany, F.R.); Wolf, R; Zscherpe, G [Ingenieurhochschule Mittweida (Germany, F.R.); Heyer, H [Sektion Physik, Friedrich-Schiller-Univ. Jena (Germany, F.R.)

    1990-11-01

    Optical coatings of titania (TiO{sub 2}) and tantala (Ta{sub 2}O{sub 5}) prepared by reactive r.f. diode and d.c. plasmatron sputtering were investigated for the influence of structural properties on the 1064 nm laser damage resistance. Using various methods of characterizing the compositional, crystallographic, microstructural and optical properties, it was found that the damage thresholds are directly related to the content of oxygen in the films in excess of the stoichiometric values, whereas grain sizes and refractive indices show no systematic influences valid for both oxide materials. The highest oxygen-to-metal atomic ratios and thus the highest damage threshold were achieved by the use of r.f diode sputtering. X-ray photospectroscopy investigations of tantala coatings with different oxygen-to-tantalum atomic ratios up to 2.75 revealed for both constituents of the oxide only binding energies representative for tantalum pentoxide. (orig.).

  12. Recent advances in Phytosterol Oxidation Products.

    Science.gov (United States)

    O'Callaghan, Yvonne; McCarthy, Florence O; O'Brien, Nora M

    2014-04-11

    Phytosterols and their oxidation products have become increasingly investigated in recent years with respect to their roles in diet and nutrition. We present a comprehensive review of recent literature on Phytosterol Oxidation Products (POP) identifying critical areas for future investigation. It is evident that POP are formed on food storage/preparation; are absorbed and found in human serum; do not directly affect cholesterol absorption; have evidence of atherogenicity and inflammation; have distinct levels of cytotoxicity; are implicated with high levels of oxidative stress, glutathione depletion, mitochondrial dysfunction and elevated caspase activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Processing of free radical damaged DNA bases

    International Nuclear Information System (INIS)

    Wallace, S.

    2003-01-01

    while cells overexpressing one of the oxidative DNA glycosylases are radiosensitive. Human TK6 lymphoblastoid cells overexpressing the oxidative DNA glycosylases are also radiosensitive. Furthermore, both radioresistance and radiosensitivity correlated with the enzymatic production of double strand breaks produced after irradiation during attempted repair. Because these data indicated the potential harmful effects of the ordinarily beneficial presence of the oxidative DNA glycosylases after treatment of cells with ionizing radiation, it was of interest to see if the base excision repair enzymes were induced by ionizing radiation. We found that ionizing radiation does not induce the oxidative DNA glycosylases in either bacterial or in human TK6 lymphoblastoid cells. Interestingly, during this past year, three novel DNA glycosylases that recognize free radical-damaged bases have been identified. The characterization of these activities will also be discussed

  14. DNA damage and defence gene expression after oxidative stress induced by x-rays and diesel exhaust particles

    Energy Technology Data Exchange (ETDEWEB)

    Risom, Lotte

    2004-07-01

    Particulate air pollution is one the most important environmental health factors for people living in cities. Especially the exhaust particles from traffic are possible causes for cancer and cardiopulmonary diseases. The aim of this thesis was to characterize the health effects of diesel exhaust particles (DEP) by inducing oxidative stress and analyse the underlying mechanisms. Methods for determining oxidative stress, DNA damage, and gene expression were validated and calibrated in lung tissue by studying the dose response relations after ionizing radiation. The study showed the feasibility of partial-body x-ray irradiation as an in vivo model for induction and repair of oxidative DNA damage, of DNA repair enzymes expression, and antioxidant defense genes. A 'nose-only' mouse model for inhalation of ultra-fine particles showed that particles induce oxidative DNA damage in lung tissue and in bronchoalveolar lavage cells. The exposure increased the expression of HO-1 mRNA and oxoguanine DNA glycosylase OGG1 mRNA. The levels of 8-oxodG and OGG1 mRNA were mirror images. Colon and liver were analysed after administration of DEP in the diet with or without increasing doses of sucrose. This study indicated that DEP induces DNA adducts and oxidative stress through formation of DNA strand breaks, DNA repair enzyme expression, apoptosis, and protein oxidisation in colon and liver at relatively low exposure doses. The thesis is based on four published journal articles. (ln)

  15. DNA damage and defence gene expression after oxidative stress induced by x-rays and diesel exhaust particles

    International Nuclear Information System (INIS)

    Risom, Lotte

    2004-01-01

    Particulate air pollution is one the most important environmental health factors for people living in cities. Especially the exhaust particles from traffic are possible causes for cancer and cardiopulmonary diseases. The aim of this thesis was to characterize the health effects of diesel exhaust particles (DEP) by inducing oxidative stress and analyse the underlying mechanisms. Methods for determining oxidative stress, DNA damage, and gene expression were validated and calibrated in lung tissue by studying the dose response relations after ionizing radiation. The study showed the feasibility of partial-body x-ray irradiation as an in vivo model for induction and repair of oxidative DNA damage, of DNA repair enzymes expression, and antioxidant defense genes. A 'nose-only' mouse model for inhalation of ultra-fine particles showed that particles induce oxidative DNA damage in lung tissue and in bronchoalveolar lavage cells. The exposure increased the expression of HO-1 mRNA and oxoguanine DNA glycosylase OGG1 mRNA. The levels of 8-oxodG and OGG1 mRNA were mirror images. Colon and liver were analysed after administration of DEP in the diet with or without increasing doses of sucrose. This study indicated that DEP induces DNA adducts and oxidative stress through formation of DNA strand breaks, DNA repair enzyme expression, apoptosis, and protein oxidisation in colon and liver at relatively low exposure doses. The thesis is based on four published journal articles. (ln)

  16. Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes

    Directory of Open Access Journals (Sweden)

    Ramesh C. Gupta

    2008-03-01

    Full Text Available DNA damage is a pre-requisite for the initiation of cancer and agents that reduce this damage are useful in cancer prevention. In this study, we evaluated the ability of whole berries and berry phytochemical, ellagic acid to reduce endogenous oxidative DNA damage. Ellagic acid was selected based on > 95% inhibition of 8-oxodeoxyguosine (8-oxodG and other unidentified oxidative DNA adducts induced by 4-hydroxy-17B;-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 u(microM than that for 8-oxodG (100 u(microM. In the in vivo study, female CD-1 mice (n=6 were fed either a control diet or diet supplemented with ellagic acid (400 ppm and dehydrated berries (5% w/w with varying ellagic acid contents -- blueberry (low, strawberry (medium and red raspberry (high, for 3 weeks. Blueberry and strawberry diets showed moderate reductions in endogenous DNA adducts (25%. However, both red raspberry and ellagic acid diets showed a significant reduction of 59% (p < 0.001 and 48% (p < 0.01, respectively. Both diets also resulted in a 3-8 fold over-expression of genes involved in DNA repair such as xeroderma pigmentosum group A complementing protein (XPA, DNA excision repair protein (ERCC5 and DNA ligase III (DNL3. These results suggest that red raspberry and ellagic acid reduce endogenous oxidative DNA damage by mechanisms which may involve increase in DNA repair.

  17. Oxidative damage in response to natural levels of UV-B radiation in larvae of the tropical sea urchin Tripneustes gratilla.

    Science.gov (United States)

    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.

  18. Effect of recoiled O on damage regrowth and electrical properties of through-oxide implanted Si

    International Nuclear Information System (INIS)

    Sadana, D.K.; Wu, N.R.; Washburn, J.; Current, M.; Morgan, A.; Reed, D.; Maenpaa, M.

    1982-10-01

    High dose (4 to 7.5 x 10 15 cm -2 ) As implantations into p-type (100) Si have been carried out through a screen-oxide of thicknesses less than or equal to 775A and without screen oxide. The effect of recoiled O on damage annealing and electrical properties of the implanted layers has been investigated using a combination of the following techniques: TEM, RBS/MeV He + channeling, SIMS and Hall measurements in conjunction with chemical stripping and sheet resistivity measurements. The TEM results show that there is a dramatically different annealing behavior of the implantation damage for the through oxide implants (Case I) as compared to implants into bare silicon (Case II). Comparison of the structural defect profiles with O distributions obtained by SIMS demonstrated that retardation in the secondary damage growth in Case I can be directly related with the presence of O. Weak-beam TEM showed that a high density of fine defect clusters (less than or equal to 50A) were present both in Case I and Case II. The electrical profiles showed only 30% of the total As to be electrically active. The structural and electrical results have been explained by a model that entails As-O, Si-O and As-As complex formation and their interaction with the dislocations

  19. Oxidative stress damage as a detrimental factor in preterm birth pathology

    Directory of Open Access Journals (Sweden)

    Ramkumar eMenon

    2014-11-01

    Full Text Available 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 are 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 (pPROM, 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.

  20. Oxidative Stress to the Cornea, Changes in Corneal Optical Properties, and Advances in Treatment of Corneal Oxidative Injuries

    Directory of Open Access Journals (Sweden)

    Cestmir Cejka

    2015-01-01

    Full Text Available Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown.

  1. Radiation-induced oxidative damage to the DNA-binding domain of the lactose repressor

    Czech Academy of Sciences Publication Activity Database

    Gillard, N.; Goffinont, S.; Buré, C.; Davídková, Marie; Maurizot, J. C.; Cadene, M.; Spotheim-Maurizot, M.

    2007-01-01

    Roč. 403, part 3 (2007), s. 463-472 ISSN 0264-6021 R&D Projects: GA MŠk 1P05OC085 Institutional research plan: CEZ:AV0Z10480505 Keywords : ionizing radiation * oxidative damage * DNA binding domain * lac repressor Subject RIV: CE - Biochemistry Impact factor: 4.009, year: 2007

  2. FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage.

    Science.gov (United States)

    Bigarella, Carolina L; Li, Jianfeng; Rimmelé, Pauline; Liang, Raymond; Sobol, Robert W; Ghaffari, Saghi

    2017-02-17

    Accumulation of damaged DNA in hematopoietic stem cells (HSC) is associated with chromosomal abnormalities, genomic instability, and HSC aging and might promote hematological malignancies with age. Despite this, the regulatory pathways implicated in the HSC DNA damage response have not been fully elucidated. One of the sources of DNA damage is reactive oxygen species (ROS) generated by both exogenous and endogenous insults. Balancing ROS levels in HSC requires FOXO3, which is an essential transcription factor for HSC maintenance implicated in HSC aging. Elevated ROS levels result in defective Foxo3 -/- HSC cycling, among many other deficiencies. Here, we show that loss of FOXO3 leads to the accumulation of DNA damage in primitive hematopoietic stem and progenitor cells (HSPC), associated specifically with reduced expression of genes implicated in the repair of oxidative DNA damage. We provide further evidence that Foxo3 -/- HSPC are defective in DNA damage repair. Specifically, we show that the base excision repair pathway, the main pathway utilized for the repair of oxidative DNA damage, is compromised in Foxo3 -/- primitive hematopoietic cells. Treating mice in vivo with N -acetylcysteine reduces ROS levels, rescues HSC cycling defects, and partially mitigates HSPC DNA damage. These results indicate that DNA damage accrued as a result of elevated ROS in Foxo3 -/- mutant HSPC is at least partially reversible. Collectively, our findings suggest that FOXO3 serves as a protector of HSC genomic stability and health. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Parental exposure to the herbicide diuron results in oxidative DNA damage to germinal cells of the Pacific oyster Crassostrea gigas.

    Science.gov (United States)

    Barranger, Audrey; Heude-Berthelin, Clothilde; Rouxel, Julien; Adeline, Béatrice; Benabdelmouna, Abdellah; Burgeot, Thierry; Akcha, Farida

    2016-02-01

    Chemical pollution by pesticides has been identified as a possible contributing factor to the massive mortality outbreaks observed in Crassostrea gigas for several years. A previous study demonstrated the vertical transmission of DNA damage by subjecting oyster genitors to the herbicide diuron at environmental concentrations during gametogenesis. This trans-generational effect occurs through damage to genitor-exposed gametes, as measured by the comet-assay. The presence of DNA damage in gametes could be linked to the formation of DNA damage in other germ cells. In order to explore this question, the levels and cell distribution of the oxidized base lesion 8-oxodGuo were studied in the gonads of exposed genitors. High-performance liquid chromatography coupled with UV and electrochemical detection analysis showed an increase in 8-oxodGuo levels in both male and female gonads after exposure to diuron. Immunohistochemistry analysis showed the presence of 8-oxodGuo at all stages of male germ cells, from early to mature stages. Conversely, the oxidized base was only present in early germ cell stages in female gonads. These results indicate that male and female genitors underwent oxidative stress following exposure to diuron, resulting in DNA oxidation in both early germ cells and gametes, such as spermatozoa, which could explain the transmission of diuron-induced DNA damage to offspring. Furthermore, immunostaining of early germ cells seems indicates that damages caused by exposure to diuron on germ line not only affect the current sexual cycle but also could affect future gametogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Characterization of coal fly ash nanoparticles and induced oxidative DNA damage in human peripheral blood mononuclear cells

    International Nuclear Information System (INIS)

    Dwivedi, Sourabh; Saquib, Quaiser; Al-Khedhairy, Abdulaziz A.; Ali, Al-Yousef Sulaiman; Musarrat, Javed

    2012-01-01

    The nano-sized particles present in coal fly ash (CFA) were characterized through the X-ray diffraction (XRD), transmission and scanning electron microscopy (TEM, SEM), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) analyses. The XRD data revealed the average crystallite size of the CFA nanoparticles (CFA-NPs) as 14 nm. TEM and SEM imaging demonstrated predominantly spherical and some polymorphic structures in the size range of 11 to 25 nm. The amount of heavy metal associated with CFA particles (μg/g) were determined as Fe (34160.0 ± 1.38), Ni (150.8 ± 0.78), Cu (99.3 ± 0.56) and Cr (64.0 ± 0.86). However, the bioavailability of heavy metals in terms of percent release was in the order as Cr > Ni > Cu > Fe in CFA-dimethyl sulfoxide (DMSO) extract. The comet and cytokinesis blocked micronucleus (CBMN) assays revealed substantial genomic DNA damage in peripheral blood mononuclear (PBMN) cells treated with CFA-NPs in Aq and DMSO extracts. About 1.8 and 3.6 strand breaks per unit of DNA were estimated through alkaline unwinding assay at 1:100 DNA nucleotide/CFA ppm ratios with the Aq and DMSO extracts, respectively. The DNA and mitochondrial damage was invariably greater with CFA-DMSO extract vis-à-vis -Aq extract. Generation of superoxide anions (O 2 • − ) and intracellular reactive oxygen species (ROS) through metal redox-cycling, alteration in mitochondrial potential and 8-oxodG production elucidated CFA-NPs induced oxidative stress as a plausible mechanism for CFA-induced genotoxicity. -- Highlights: ► CFA consists of spherical crystalline nanoparticles in size range of 11–25 nm. ► Alkaline unwinding assay revealed single-strandedness in CFA treated ctDNA. ► CFA nanoparticles exhibited the ability to induce ROS and oxidative DNA damage. ► Comet and CBMN assays revealed DNA and chromosomal breakage in PBMN cells. ► CFA-NPs resulted in mitochondrial membrane damage in PBMN cells.

  5. Characterization of coal fly ash nanoparticles and induced oxidative DNA damage in human peripheral blood mononuclear cells

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, Sourabh; Saquib, Quaiser; Al-Khedhairy, Abdulaziz A. [Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Ali, Al-Yousef Sulaiman [Department of Medical Laboratory Sciences, College of Applied Medical Science, University of Dammam, P.O. Box 1683, Hafr Al Batin-31991 (Saudi Arabia); Musarrat, Javed, E-mail: musarratj1@yahoo.com [Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Agricultural Microbiology, Faculty of Agricultural Sciences, AMU, Aligarh202002 (India)

    2012-10-15

    The nano-sized particles present in coal fly ash (CFA) were characterized through the X-ray diffraction (XRD), transmission and scanning electron microscopy (TEM, SEM), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) analyses. The XRD data revealed the average crystallite size of the CFA nanoparticles (CFA-NPs) as 14 nm. TEM and SEM imaging demonstrated predominantly spherical and some polymorphic structures in the size range of 11 to 25 nm. The amount of heavy metal associated with CFA particles ({mu}g/g) were determined as Fe (34160.0 {+-} 1.38), Ni (150.8 {+-} 0.78), Cu (99.3 {+-} 0.56) and Cr (64.0 {+-} 0.86). However, the bioavailability of heavy metals in terms of percent release was in the order as Cr > Ni > Cu > Fe in CFA-dimethyl sulfoxide (DMSO) extract. The comet and cytokinesis blocked micronucleus (CBMN) assays revealed substantial genomic DNA damage in peripheral blood mononuclear (PBMN) cells treated with CFA-NPs in Aq and DMSO extracts. About 1.8 and 3.6 strand breaks per unit of DNA were estimated through alkaline unwinding assay at 1:100 DNA nucleotide/CFA ppm ratios with the Aq and DMSO extracts, respectively. The DNA and mitochondrial damage was invariably greater with CFA-DMSO extract vis-a-vis -Aq extract. Generation of superoxide anions (O{sub 2} Bullet {sup -}) and intracellular reactive oxygen species (ROS) through metal redox-cycling, alteration in mitochondrial potential and 8-oxodG production elucidated CFA-NPs induced oxidative stress as a plausible mechanism for CFA-induced genotoxicity. -- Highlights: Black-Right-Pointing-Pointer CFA consists of spherical crystalline nanoparticles in size range of 11-25 nm. Black-Right-Pointing-Pointer Alkaline unwinding assay revealed single-strandedness in CFA treated ctDNA. Black-Right-Pointing-Pointer CFA nanoparticles exhibited the ability to induce ROS and oxidative DNA damage. Black-Right-Pointing-Pointer Comet and CBMN assays revealed DNA and chromosomal

  6. Kombucha Tea Ameliorates Trichloroethylene Induced Hepatic Damages in Rats via Inhibition of Oxidative Stress and Free Radicals Induction

    International Nuclear Information System (INIS)

    Gharib, O.A.; Gharib, M.A.

    2008-01-01

    Kombucha Tea (KT) is reported to exhibit a wide variety of biological effects, including antioxidant. Evidence shows the important role of oxidative stress in the hepatic damage. The aim of this study is to investigate the possible protective effects of oral administration of KT in rats with trichloroethylene (TCE)-induced damage for ten consecutive days. Hepatic damage was evaluated by measuring total free radicals levels, biochemical and histological examinations. Serum gamma glutamyl transferase (GGT) activity (the hepatic damage marker), total protein, albumin and globulin as well as malonaldehyde (MDA), glutathione (GSH) content, nitric oxide (NO) concentration were evaluated in liver tissue homogenates. Total free radicals concentration in blood was examined by electron spin resonance (ESR). Total protein, DNA concentration, cell number and cell size in liver tissues were also examined. The rats orally administrated with TCE for ten days indicates hepatic damage changes, an increase in blood total free radicals concentration was observed, serum GGT activity, liver MDA, NO levels, total protein and decreased GSH content, DNA concentration and cell number. This accompanied with an increase in cell size of liver tissues, whereas KT reversed these effects. Furthermore, KT inhibits the concentration of total free radicals in blood and decreasing the increment of MDA and NO concentration. Histological studies reveal partial healing in those rats treated by KT after oral administration with TCE. The present results suggest that KT ameliorates TCE induced hepatic damage in rats probably due to its content of glucuronic, acetic acid and B vitamins via inhibition of oxidative stress and total free radicals

  7. Articulation of Native Cartilage Against Different Femoral Component Materials. Oxidized Zirconium Damages Cartilage Less Than Cobalt-Chrome.

    Science.gov (United States)

    Vanlommel, Jan; De Corte, Ronny; Luyckx, Jean Philippe; Anderson, Melissa; Labey, Luc; Bellemans, Johan

    2017-01-01

    Oxidized zirconium (OxZr) is produced by thermally driven oxidization creating an oxidized surface with the properties of a ceramic at the top of the Zr metal substrate. OxZr is much harder and has a lower coefficient of friction than cobalt-chrome (CoCr), both leading to better wear characteristics. We evaluated and compared damage to the cartilage of porcine patella plugs, articulating against OxZr vs CoCr. Our hypothesis was that, owing to its better wear properties, OxZr would damage cartilage less than CoCr. If this is true, OxZr might be a better material for the femoral component during total knee arthroplasty if the patella is not resurfaced. Twenty-one plugs from porcine patellae were prepared and tested in a reciprocating pin-on-disk machine while lubricated with bovine serum and under a constant load. Three different configurations were tested: cartilage-cartilage as the control group, cartilage-OxZr, and cartilage-CoCr. Macroscopic appearance, cartilage thickness, and the modified Mankin score were evaluated after 400,000 wear cycles. The control group showed statistically significant less damage than plugs articulating against both other materials. Cartilage plugs articulating against OxZr were statistically significantly less damaged than those articulating against CoCr. Although replacing cartilage by an implant always leads to deterioration of the cartilage counterface, OxZr results in less damage than CoCr. The use of OxZr might thus be preferable to CoCr in case of total knee arthroplasty without patella resurfacing. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    Directory of Open Access Journals (Sweden)

    Stephanie Puukila

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  10. Base excision repair of both uracil and oxidatively damaged bases contribute to thymidine deprivation-induced radiosensitization

    International Nuclear Information System (INIS)

    Allen, Bryan G.; Johnson, Monika; Marsh, Anne E.; Dornfeld, Kenneth J.

    2006-01-01

    Purpose: Increased cellular sensitivity to ionizing radiation due to thymidine depletion is the basis of radiosensitization with fluoropyrimidine and methotrexate. The mechanism responsible for cytotoxicity has not been fully elucidated but appears to involve both the introduction of uracil into, and its removal from, DNA. The role of base excision repair of uracil and oxidatively damaged bases in creating the increased radiosensitization during thymidine depletion is examined. Methods and Materials: Isogenic strains of S. cerevisiae differing only at loci involved in DNA repair functions were exposed to aminopterin and sulfanilamide to induce thymidine deprivation. Cultures were irradiated and survival determined by clonogenic survival assay. Results: Strains lacking uracil base excision repair (BER) activities demonstrated less radiosensitization than the parental strain. Mutant strains continued to show partial radiosensitization with aminopterin treatment. Mutants deficient in BER of both uracil and oxidatively damaged bases did not demonstrate radiosensitization. A recombination deficient rad52 mutant strain was markedly sensitive to radiation; addition of aminopterin increased radiosensitivity only slightly. Radiosensitization observed in rad52 mutants was also abolished by deletion of the APN1, NTG1, and NTG2 genes. Conclusion: These data suggest radiosensitization during thymidine depletion is the result of BER activities directed at both uracil and oxidatively damaged bases

  11. Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

    Science.gov (United States)

    Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

    2015-12-01

    Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (pmicrowave exposed groups (pmicrowave exposed animal (pmicrowave exposed groups as compared to their corresponding values in sham exposed group (pmicrowave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Methods for forming complex oxidation reaction products including superconducting articles

    International Nuclear Information System (INIS)

    Rapp, R.A.; Urquhart, A.W.; Nagelberg, A.S.; Newkirk, M.S.

    1992-01-01

    This patent describes a method for producing a superconducting complex oxidation reaction product of two or more metals in an oxidized state. It comprises positioning at least one parent metal source comprising one of the metals adjacent to a permeable mass comprising at least one metal-containing compound capable of reaction to form the complex oxidation reaction product in step below, the metal component of the at least one metal-containing compound comprising at least a second of the two or more metals, and orienting the parent metal source and the permeable mass relative to each other so that formation of the complex oxidation reaction product will occur in a direction towards and into the permeable mass; and heating the parent metal source in the presence of an oxidant to a temperature region above its melting point to form a body of molten parent metal to permit infiltration and reaction of the molten parent metal into the permeable mass and with the oxidant and the at least one metal-containing compound to form the complex oxidation reaction product, and progressively drawing the molten parent metal source through the complex oxidation reaction product towards the oxidant and towards and into the adjacent permeable mass so that fresh complex oxidation reaction product continues to form within the permeable mass; and recovering the resulting complex oxidation reaction product

  13. Proceedings of damage and oxidation protection in high temperature composites

    International Nuclear Information System (INIS)

    Haritos, G.K.; Ochoa, O.O.

    1991-01-01

    This book contains proceedings of Damage and Oxidation Protection in High Temperature Composites. Topics covered include: current issues in the development of new materials and structural concepts for the aerospace structures of the future; transportation vehicles of the future; materials and structural concepts; fundamental understanding and quantitative descriptions of the physical processes and mechanisms controlling the behavior of emerging materials and structures; and the critical need for advances in our understanding of how the interaction of service loads and environment influences the lifecycle of emerging structures and materials

  14. Screening for oxidative damage by engineered nanomaterials: a comparative evaluation of FRAS and DCFH

    Science.gov (United States)

    Pal, Anoop K.; Hsieh, Shu-Feng; Khatri, Madhu; Isaacs, Jacqueline A.; Demokritou, Philip; Gaines, Peter; Schmidt, Daniel F.; Rogers, Eugene J.; Bello, Dhimiter

    2014-02-01

    Several acellular assays are routinely used to measure oxidative stress elicited by engineered nanomaterials (ENMs), yet little comparative evaluations of such methods exist. This study compares for the first time the performance of the dichlorofluorescein (DCFH) assay which measures reactive oxygen species (ROS) generation, to that of the ferric-reducing ability of serum (FRAS) assay, which measures biological oxidant damage in serum. A diverse set of 28 commercially important and extensively characterized ENMs were tested on both the assays. Intracellular oxidative stress was also assessed on a representative subset of seven ENMs in THP-1 (phorbol 12-myristate 13-acetate matured human monocytes) cells. Associations between assay responses and ENM physicochemical properties were assessed via correlation and regression analysis. DCFH correlated strongly with FRAS after dose normalization for mass ( R 2 = 0.78) and surface area ( R 2 = 0.68). Only 10/28 ENMs were positive in DCFH versus 21/28 in FRAS. Both assays were strongly associated with specific surface area and transition metal content. Qualitatively, a similar response ranking was observed for acellular FRAS and intracellular reduced:oxidized glutathione ratio (GSH:GSSG) in cells. Quantitatively, weak correlation was found between intracellular GSSG and FRAS or DCFH ( R 2 < 0.25) even after calculating effective dose to cells. The FRAS assay was more sensitive than DCFH, especially for ENMs with low to moderate oxidative damage potential, and may serve as a more biologically relevant substitute for acellular ROS measurements of ENMs. Further in vitro and in vivo validations of FRAS against other toxicological endpoints with larger datasets are recommended.

  15. Assessment of the Antioxidant Activity of Silybum marianum Seed Extract and Its Protective Effect against DNA Oxidation, Protein Damage and Lipid Peroxidation

    Directory of Open Access Journals (Sweden)

    Aynur Serçe

    2016-01-01

    Full Text Available Antioxidant properties of ethanol extract of Silybum marianum (milk thistle seeds was investigated. We have also investigated the protein damage activated by oxidative Fenton reaction and its prevention by Silybum marianum seed extract. Antioxidant potential of Silybum marianum seed ethanol extract was measured using diff erent in vitro methods, such as lipid peroxidation, 1,1–diphenyl–2–picrylhydrazyl (DPPH and ferric reducing power assays. The extract significantly decreased DNA damage caused by hydroxyl radicals. Protein damage induced by hydroxyl radicals was also effi ciently inhibited, which was confirmed by the presence of protein damage markers, such as protein carbonyl formation and by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE. The present study shows that milk thistle seeds have good DPPH free radical scavenging activity and can prevent lipid peroxidation. Therefore, Silybum marianum can be used as potentially rich source of antioxidants and food preservatives. The results suggest that the seeds may have potential beneficial health effects providing opportunities to develop value-added products.

  16. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats.

    Science.gov (United States)

    Chowdhury, Mohammed Riaz Hasan; Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Hossain, Hemayet; Alam, Md Ashraful

    2015-01-01

    Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (-)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

  17. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4 Treated Rats

    Directory of Open Access Journals (Sweden)

    Mohammed Riaz Hasan Chowdhury

    2015-01-01

    Full Text Available Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (−-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4 treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA, nitric oxide, advanced protein oxidation products level (APOP, and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

  18. Ghrelin Pre-treatment Attenuates Local Oxidative Stress and End Organ Damage During Cardiopulmonary Bypass in Anesthetized Rats

    Science.gov (United States)

    Sukumaran, Vijayakumar; Tsuchimochi, Hirotsugu; Fujii, Yutaka; Hosoda, Hiroshi; Kangawa, Kenji; Akiyama, Tsuyoshi; Shirai, Mikiyasu; Tatsumi, Eisuke; Pearson, James T.

    2018-01-01

    Cardiopulmonary bypass (CPB) induced systemic inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately can lead to failure of multiple organs. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. Herein, we investigated the protective effects of ghrelin against CPB-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male Sprague Dawley rats randomly received vehicle (n = 5) or a bolus of ghrelin (150 μg/kg, sc, n = 5) and were subjected to CPB for 4 h (protocol 1). In separate rats, ghrelin pre-treatment (protocol 2) was compared to two doses of ghrelin (protocol 3) before and after CPB for 2 h followed by recovery for 2 h. Blood samples were taken prior to CPB, and following CPB at 2 h and 4 h. Organ nitrosative stress (3-nitrotyrosine) was measured by Western blotting. CPB induced leukocytosis with increased plasma levels of tumor necrosis factor-α and interleukin-6 indicating a potent inflammatory response. Ghrelin treatment significantly reduced plasma organ damage markers (lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase) and protein levels of 3-nitrotyrosine, particularly in the brain, lung and liver, but only partly suppressed inflammatory cell invasion and did not reduce proinflammatory cytokine production. Ghrelin partially attenuated the CPB-induced elevation of epinephrine and to a lesser extent norepinephrine when compared to the CPB saline group, while dopamine levels were completely suppressed. Ghrelin treatment sustained plasma levels of reduced glutathione and decreased glutathione disulphide when compared to CPB saline rats. These results suggest that even though ghrelin only partially inhibited the large CPB induced increase in catecholamines and organ macrophage infiltration, it reduced oxidative

  19. Personal exposure to ultrafine particles and oxidative DNA damage

    DEFF Research Database (Denmark)

    Vinzents, Peter S; Møller, Peter; Sørensen, Mette

    2005-01-01

    Exposure to ultrafine particles (UFPs) from vehicle exhaust has been related to risk of cardiovascular and pulmonary disease and cancer, even though exposure assessment is difficult. We studied personal exposure in terms of number concentrations of UFPs in the breathing zone, using portable instr......, particularly during bicycling in traffic. The results indicate that biologic effects of UFPs occur at modest exposure, such as that occurring in traffic, which supports the relationship of UFPs and the adverse health effects of air pollution.......Exposure to ultrafine particles (UFPs) from vehicle exhaust has been related to risk of cardiovascular and pulmonary disease and cancer, even though exposure assessment is difficult. We studied personal exposure in terms of number concentrations of UFPs in the breathing zone, using portable...... instruments in six 18-hr periods in 15 healthy nonsmoking subjects. Exposure contrasts of outdoor pollution were achieved by bicycling in traffic for 5 days and in the laboratory for 1 day. Oxidative DNA damage was assessed as strand breaks and oxidized purines in mononuclear cells isolated from venous blood...

  20. Protective Effect of Edaravone Against Aβ25-35-Induced Mitochondrial Oxidative Damage in SH-SY5Y Cells.

    Science.gov (United States)

    Zhang, G-L; Zhang, L; Guo, Y-Y; Ma, Z-L; Wang, H-Y; Li, T; Liu, J; Du, Y; Yao, L; Li, T-T; Du, J-M

    2017-05-20

    Amyloid-β (Aβ)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aβ accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aβ25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 μM edaravone before treatment with 25 μM Aβ25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated. SH-SY5Y cells exposed to Aβ25-35 had high levels of apoptosis and ROS; loss of ΔΨm, decreased ATP levels and presence of mitochondrial swelling. However, these effects were significantly inhibited by edaravone pre-treatment. These results indicate that edaravone prevents mitochondria oxidative damage caused by Aβ in SH-SY5Y cells, which suggests that it may have potential clinical application in AD therapy.

  1. Endothelial nitric oxide synthase gene polymorphisms and cardiovascular damage in hypertensive subjects: an Italian case-control study

    Directory of Open Access Journals (Sweden)

    Pizzo Federica

    2008-05-01

    Full Text Available Abstract Background Nitric oxide (NO synthesized by endothelial nitric oxide synthase (eNOS plays an important role in regulation of endothelial function and in the control of blood pressure. However, the results from some studies on the association between three clinically relevant eNOS gene polymorphisms (G894T, T786C and intron 4b/a and essential hypertension are unclear. We designed a case-control study to evaluate the influence of eNOS polymorphisms on target organ damage in 127 hypertensives and 67 normotensives. Clinical evaluation, biochemical parameters, Urinary Albumin Excretion (UAE and echocardiogram were performed to characterize target organ damage. eNOS polymorphism were recognized by PCR method. Results The distribution of eNOS genotypes was similar in hypertensives and normotensives but 4aa was present in the 2.5% of hypertensives and completely absent in normotensives. Subjects with 4bb, G894T, and T786C genotypes showed an increased prevalence of target organ damage. Moreover prevalence of G894T and introne 4 variants was significantly higher in hypertensives than in normotensives both with cardiovascular damage. Logistic regression analysis didn't show any association between eNOS polymorphisms, Body Mass Index (BMI, hypertension, gender and cardiovascular damage. Only the age (OR 1.11; IC 95% 1.06–1.18 was predictive of cardiovascular damage in our population. Conclusion Our results seem to indicate a lack of association with eNOS variants and cardiovascular damage onset.

  2. Oxidative damage of U937 human leukemic cells caused by hydroxyl radical results in singlet oxygen formation.

    Directory of Open Access Journals (Sweden)

    Marek Rác

    Full Text Available The exposure of human cells to oxidative stress leads to the oxidation of biomolecules such as lipids, proteins and nuclei acids. In this study, the oxidation of lipids, proteins and DNA was studied after the addition of hydrogen peroxide and Fenton reagent to cell suspension containing human leukemic monocyte lymphoma cell line U937. EPR spin-trapping data showed that the addition of hydrogen peroxide to the cell suspension formed hydroxyl radical via Fenton reaction mediated by endogenous metals. The malondialdehyde HPLC analysis showed no lipid peroxidation after the addition of hydrogen peroxide, whereas the Fenton reagent caused significant lipid peroxidation. The formation of protein carbonyls monitored by dot blot immunoassay and the DNA fragmentation measured by comet assay occurred after the addition of both hydrogen peroxide and Fenton reagent. Oxidative damage of biomolecules leads to the formation of singlet oxygen as conformed by EPR spin-trapping spectroscopy and the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. It is proposed here that singlet oxygen is formed by the decomposition of high-energy intermediates such as dioxetane or tetroxide formed by oxidative damage of biomolecules.

  3. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude...... that the DDR machinery is constitutively activated in gliomas, as documented by phosphorylated histone H2AX (gammaH2AX), activation of the ATM-Chk2-p53 pathway, 53BP1 foci and other markers. Oxidative DNA damage (8-oxoguanine) was high in some GBM cell lines and many GBM tumors, while it was low in normal...... brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...

  4. 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.

    Directory of Open Access Journals (Sweden)

    Stefania Casagrande

    Full Text Available 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.

  5. From Oxidative Stress Damage to Pathways, Networks, and Autophagy via MicroRNAs

    Directory of Open Access Journals (Sweden)

    Nikolai Engedal

    2018-01-01

    Full Text Available Oxidative stress can alter the expression level of many microRNAs (miRNAs, but how these changes are integrated and related to oxidative stress responses is poorly understood. In this article, we addressed this question by using in silico tools. We reviewed the literature for miRNAs whose expression is altered upon oxidative stress damage and used them in combination with various databases and software to predict common gene targets of oxidative stress-modulated miRNAs and affected pathways. Furthermore, we identified miRNAs that simultaneously target the predicted oxidative stress-modulated miRNA gene targets. This generated a list of novel candidate miRNAs potentially involved in oxidative stress responses. By literature search and grouping of pathways and cellular responses, we could classify these candidate miRNAs and their targets into a larger scheme related to oxidative stress responses. To further exemplify the potential of our approach in free radical research, we used our explorative tools in combination with ingenuity pathway analysis to successfully identify new candidate miRNAs involved in the ubiquitination process, a master regulator of cellular responses to oxidative stress and proteostasis. Lastly, we demonstrate that our approach may also be useful to identify novel candidate connections between oxidative stress-related miRNAs and autophagy. In summary, our results indicate novel and important aspects with regard to the integrated biological roles of oxidative stress-modulated miRNAs and demonstrate how this type of in silico approach can be useful as a starting point to generate hypotheses and guide further research on the interrelation between miRNA-based gene regulation, oxidative stress signaling pathways, and autophagy.

  6. Oxidative DNA damage in bone marrow cells of patients with low-risk myelodysplastic syndrome

    Czech Academy of Sciences Publication Activity Database

    Novotná, Božena; Bagryantseva, Yana; Šišková, M.; Neuwirtová, R.

    2009-01-01

    Roč. 33, č. 2 (2009), s. 340-343 ISSN 0145-2126 R&D Projects: GA MZd NR8265 Institutional research plan: CEZ:AV0Z50390512 Keywords : Myelodysplastic syndrome * Refractory anemia * Oxidative DNA damage Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.358, year: 2009

  7. DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

    Directory of Open Access Journals (Sweden)

    Fabrizio Gentile

    2017-04-01

    Full Text Available Oxidative stress and lipid peroxidation (LPO induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity.

  8. A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qian; Ma, Ruonan; Tian, Ying [Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Liang, Yongdong; Feng, Hongqing [College of Engineering, Peking University, Beijing 100871 (China); Zhang, Jue; Fang, Jing [Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); College of Engineering, Peking University, Beijing 100871 (China)

    2013-05-20

    Ar/O{sub 2} (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

  9. A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

    International Nuclear Information System (INIS)

    Zhang, Qian; Ma, Ruonan; Tian, Ying; Liang, Yongdong; Feng, Hongqing; Zhang, Jue; Fang, Jing

    2013-01-01

    Ar/O 2 (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

  10. Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

    Science.gov (United States)

    Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

    2015-09-01

    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

  11. Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage

    DEFF Research Database (Denmark)

    Savorani, Cecilia; Manfé, Valentina; Biskup, Edyta

    2015-01-01

    (CTCL), a disease that is progressive, chemoresistant and refractory to treatment. We tested the effect of ellipticine in three cell lines with different p53 status: MyLa2000 (p53(wt/wt)), SeAx ((G245S)p53) and Hut-78 ((R196Stop)p53). Ellipticine caused apoptosis in MyLa2000 and SeAx and restored...... the transcriptional activity of (G245S)p53 in SeAx. However, p53 siRNA knockdown experiments revealed that p53 was not required for ellipticine-induced apoptosis in CTCL. The lipophilic antioxidant α-tocopherol inhibited ellipticine-dependent apoptosis and we linked the apoptotic response to the oxidative DNA damage....... Our results provide evidence that ellipticine-induced apoptosis is exerted through DNA damage and does not require p53 activation in T-cell lymphoma....

  12. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    International Nuclear Information System (INIS)

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min; Xing, Mingyou; Liu, Liegang; Yao, Ping

    2013-01-01

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD

  13. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Xing, Mingyou [Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Liu, Liegang [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Yao, Ping, E-mail: yaoping@mails.tjmu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China)

    2013-11-15

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD.

  14. Oxidative damage markers are significantly associated with the carotid artery intima-media thickness after controlling for conventional risk factors of atherosclerosis in men.

    Directory of Open Access Journals (Sweden)

    Jin-Ha Yoon

    Full Text Available This study aimed to assess the association between oxidative damage markers and carotid artery intima-media thickness (CIMT after controlling for conventional risk factors of atherosclerosis in multiple logistic regression models.Fifty-one case male participants (CIMT ≥ 0.9 mm were enrolled during their visits to Korean Genomic Rural Cohort Study of Wonju centers between May 1 and August 31, 2011, along with 51 control participants (CIMT < 0.9 mm selected using frequency matching by age group. The levels of oxidative damage markers, 8-hydroxy-2'-deoxyquuanosine (8-OHdG, malondialdehyde (MDA, and 8-iso-prostaglandin F2α (Isoprostane, were measured. Conditional logistic regression models were used to evaluate relative relationships between the oxidative damage markers and the risk of high CIMT.The markers of oxidative lipid (Isoprostane and MDA and DNA (8-OHdG damage were associated with CIMT after controlling for the conventional risk factors, including age, low density lipoprotein, body mass index, smoking history, alcohol consumption, and metabolic syndrome (ORs [95% CI] for Isoprostane: 3rd tertile, 8.47 [2.59-27.67]; for MDA: 3rd tertile, 8.47 [2.59-27.67]; for 8-OHdG: 3rd tertile, 5.58 [1.79-17.33]. When all the oxidative damage markers were incorporated in the same logistic regression model, only Isoprostane was significantly related to CIMT (OR [95% CI]: 4.22 [1.31-13.53] in 2nd tertile and 14.21 [3.34-60.56] in 3rd tertile.In this nested case-control study, the oxidative damage markers of lipid and DNA were associated with CIMT even after controlling for the conventional risk factors of cardiovascular diseases.

  15. Response of Lemna minor L. to short-term cobalt exposure: The effect on photosynthetic electron transport chain and induction of oxidative damage

    International Nuclear Information System (INIS)

    Begović, Lidija; Mlinarić, Selma; Antunović Dunić, Jasenka; Katanić, Zorana; Lončarić, Zdenko; Lepeduš, Hrvoje; Cesar, Vera

    2016-01-01

    Highlights: • Cobalt (Co"2"+) impaired the function of oxygen evolving complex (OEC) in L. minor L. • Electron transport through PSII components varied depending on Co"2"+ concentration. • K-band was proven to be suitable parameter for investigation of Co"2"+ toxicity. • Increased lipid peroxidation level showed early oxidative damage induced by Co"2"+. - Abstract: The effect of two concentrations of cobalt (Co"2"+) on photosynthetic activity and antioxidative response in Lemna minor L. were assessed 24, 48 and 72 h after the start of the exposure. Higher concentration of cobalt (1 mM) induced growth inhibition while lower concentration (0.01 mM) increased photosynthetic pigments content. Analysis of chlorophyll a fluorescence transients revealed high sensitivity of photosystem II primary photochemistry to excess of Co"2"+ especially at the higher concentration where decreased electron transport beyond primary quinone acceptor Q_A"− and impaired function of oxygen evolving complex (OEC) was observed. Due to impairment of OEC, oxygen production was decreased at higher Co"2"+ concentration. Activity of superoxide dismutase was mainly inhibited while lipid peroxidation increased, at both concentrations, indicating that cobalt-induced oxidative damage after short exposure and moreover, susceptibility of the membranes in the cell to cobalt toxicity. Results obtained in this study suggest possible application of used parameters as tools in assessment of early damage caused by metals.

  16. Structural and electrical characterization of HBr/O{sub 2} plasma damage to Si substrate

    Energy Technology Data Exchange (ETDEWEB)

    Fukasawa, Masanaga; Nakakubo, Yoshinori; Matsuda, Asahiko; Takao, Yoshinori; Eriguchi, Koji; Ono, Kouichi; Minami, Masaki; Uesawa, Fumikatsu; Tatsumi, Tetsuya [Semiconductor Technology Development Division, Semiconductor Business Group, Professional, Device and Solutions Group, Sony Corporation, 4-14-1 Asahi-cho, Atsugi-shi, Kanagawa 243-0014 (Japan); Department of Aeronautics and Astronautics, Graduate School of Engineering, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan); Semiconductor Technology Development Division, Semiconductor Business Group, Professional, Device and Solutions Group, Sony Corporation, 4-14-1 Asahi-cho, Atsugi-shi, Kanagawa 243-0014 (Japan)

    2011-07-15

    Silicon substrate damage caused by HBr/O{sub 2} plasma exposure was investigated by spectroscopic ellipsometry (SE), high-resolution Rutherford backscattering spectroscopy, and transmission electron microscopy. The damage caused by H{sub 2}, Ar, and O{sub 2} plasma exposure was also compared to clarify the ion-species dependence. Although the damage basically consists of a surface oxidized layer and underlying dislocated Si, the damage structure strongly depends on the incident ion species, ion energy, and oxidation during air and plasma exposure. In the case of HBr/O{sub 2} plasma exposure, hydrogen generated the deep damaged layer ({approx}10 nm), whereas ion-enhanced diffusion of oxygen, supplied simultaneously by the plasma, caused the thick surface oxidation. In-line monitoring of damage thicknesses by SE, developed with an optimized optical model, showed that the SE can be used to precisely monitor damage thicknesses in mass production. Capacitance-voltage (C-V) characteristics of a damaged layer were studied before and after diluted-HF (DHF) treatment. Results showed that a positive charge is generated at the surface oxide-dislocated Si interface and/or in the bulk oxide after plasma exposure. After DHF treatment, most of the positive charges were removed, while the thickness of the ''Si recess'' was increased by removing the thick surface oxidized layer. As both the Si recess and remaining dislocated Si, including positive charges, cause the degradation of electrical performance, precise monitoring of the surface structure and understanding its effect on device performance is indispensable for creating advanced devices.

  17. Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer

    Directory of Open Access Journals (Sweden)

    Hamiyet Donmez-Altuntas

    2017-01-01

    Full Text Available Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2′-deoxyguanosine (8-OHdG levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 age- and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN frequency (chromosomal DNA damage, apoptotic and necrotic cells (cytotoxicity, and plasma 8-OHdG levels (oxidative DNA damage were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer.

  18. Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage

    Directory of Open Access Journals (Sweden)

    Cun-dong Fan

    2017-12-01

    Full Text Available Homocysteine (Hcy as an independent risk factor contributes to the occurrence and development of human cardiovascular diseases (CVD. Induction of oxidative stress and apoptosis was commonly accepted as the major mechanism in Hcy-induced cardiotoxicity. Astaxanthin (ATX as one of the most powerful antioxidants exhibits novel cardioprotective potential against Hcy-induced endothelial dysfunction. However, the protective effect and mechanism of ATX against Hcy-induced cardiotoxicity in cardiomyocytes have not been elucidated yet. Herein, H9c2 rat cardiomyocytes and Hcy-injured animal model were employed in the present study. The MTT, flow cytometry analysis (FCM, TUNEL-DAPI and western blotting results all demonstrated that ATX significantly alleviated Hcy-induced cytotoxicity in H9c2 cells through inhibition of mitochondria-mediated apoptosis. The JC-1 and Mito-tracker staining both revealed that ATX pre-treatment blocked Hcy-induced mitochondrial dysfunction by regulating Bcl-2 family expression. Moreover, DCFH-DA and Mito-SOX staining showed that ATX effectively attenuated Hcy-induced oxidative damage via scavenging intracellular reactive oxygen species (ROS. Importantly, the ELISA and immunohistochemical results indicated that Hcy-induced cardiotoxicity in vivo was also significantly inhibited by ATX through inhibition of oxidative damage and apoptosis, and improvement of the angiogenesis. Taken together, our results demonstrated that ATX suppressed Hcy-induced cardiotoxicity in vitro and in vivo by inhibiting mitochondrial dysfunction and oxidative damage. Our findings validated the strategy of using ATX may be a highly efficient way to combat Hcy-mediated human CVD.

  19. Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage.

    Science.gov (United States)

    Fan, Cun-Dong; Sun, Jing-Yi; Fu, Xiao-Ting; Hou, Ya-Jun; Li, Yuan; Yang, Ming-Feng; Fu, Xiao-Yan; Sun, Bao-Liang

    2017-01-01

    Homocysteine (Hcy) as an independent risk factor contributes to the occurrence and development of human cardiovascular diseases (CVD). Induction of oxidative stress and apoptosis was commonly accepted as the major mechanism in Hcy-induced cardiotoxicity. Astaxanthin (ATX) as one of the most powerful antioxidants exhibits novel cardioprotective potential against Hcy-induced endothelial dysfunction. However, the protective effect and mechanism of ATX against Hcy-induced cardiotoxicity in cardiomyocytes have not been elucidated yet. Herein, H9c2 rat cardiomyocytes and Hcy-injured animal model were employed in the present study. The MTT, flow cytometry analysis (FCM), TUNEL-DAPI and western blotting results all demonstrated that ATX significantly alleviated Hcy-induced cytotoxicity in H9c2 cells through inhibition of mitochondria-mediated apoptosis. The JC-1 and Mito-tracker staining both revealed that ATX pre-treatment blocked Hcy-induced mitochondrial dysfunction by regulating Bcl-2 family expression. Moreover, DCFH-DA and Mito-SOX staining showed that ATX effectively attenuated Hcy-induced oxidative damage via scavenging intracellular reactive oxygen species (ROS). Importantly, the ELISA and immunohistochemical results indicated that Hcy-induced cardiotoxicity in vivo was also significantly inhibited by ATX through inhibition of oxidative damage and apoptosis, and improvement of the angiogenesis. Taken together, our results demonstrated that ATX suppressed Hcy-induced cardiotoxicity in vitro and in vivo by inhibiting mitochondrial dysfunction and oxidative damage. Our findings validated the strategy of using ATX may be a highly efficient way to combat Hcy-mediated human CVD.

  20. Reduction of oxidative cellular damage by overexpression of the thioredoxin TRX2 gene improves yield and quality of wine yeast dry active biomass

    Directory of Open Access Journals (Sweden)

    Ros Joaquim

    2010-02-01

    Full Text Available Abstract Background Wine Saccharomyces cerevisiae strains, adapted to anaerobic must fermentations, suffer oxidative stress when they are grown under aerobic conditions for biomass propagation in the industrial process of active dry yeast production. Oxidative metabolism of sugars favors high biomass yields but also causes increased oxidation damage of cell components. The overexpression of the TRX2 gene, coding for a thioredoxin, enhances oxidative stress resistance in a wine yeast strain model. The thioredoxin and also the glutathione/glutaredoxin system constitute the most important defense against oxidation. Trx2p is also involved in the regulation of Yap1p-driven transcriptional response against some reactive oxygen species. Results Laboratory scale simulations of the industrial active dry biomass production process demonstrate that TRX2 overexpression increases the wine yeast final biomass yield and also its fermentative capacity both after the batch and fed-batch phases. Microvinifications carried out with the modified strain show a fast start phenotype derived from its enhanced fermentative capacity and also increased content of beneficial aroma compounds. The modified strain displays an increased transcriptional response of Yap1p regulated genes and other oxidative stress related genes. Activities of antioxidant enzymes like Sod1p, Sod2p and catalase are also enhanced. Consequently, diminished oxidation of lipids and proteins is observed in the modified strain, which can explain the improved performance of the thioredoxin overexpressing strain. Conclusions We report several beneficial effects of overexpressing the thioredoxin gene TRX2 in a wine yeast strain. We show that this strain presents an enhanced redox defense. Increased yield of biomass production process in TRX2 overexpressing strain can be of special interest for several industrial applications.

  1. Evaluation of the water disinfection by-product dichloroacetonitrile-induced biochemical, oxidative, histopathological, and mitochondrial functional alterations: Subacute oral toxicity in rats.

    Science.gov (United States)

    Dong, Ying; Li, Fang; Shen, Haijun; Lu, Rongzhu; Yin, Siqi; Yang, Qi; Li, Zhuangfa; Wang, Suhua

    2018-03-01

    Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is more genotoxic and cytotoxic than the currently regulated carbonaceous disinfection by-products such as haloacetic acids. Few mechanistic studies have been conducted on the hepatic and renal toxicities of DCAN. This study examined the clinical biochemical, hematological, histopathological, oxidative, and mitochondrial functional alterations to evaluate the systematic toxicity after subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen weights were lower, and organ-to-body weight ratios of the liver and kidney were higher in rats administered 44-mg/kg DCAN than in controls. The activities of serum alanine aminotransferase and alkaline phosphatase, and concentrations of blood serum urea nitrogen and retinol-binding protein were increased in rats administered 44-mg/kg DCAN compared with those of controls, thereby indicating hepatic and renal damage in this group. This was confirmed by histopathological alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling, in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage shown by the significant increase in malonaldehyde levels, a poisonous product of lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic glutathione content and mitochondrial bioenergy as noted by the elevation of mitochondrial membrane potential and cytochrome c oxidase activity, which might be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic mitochondrial damage.

  2. Effect of Acetyl-L-Carnitine on Antioxidant Status, Lipid Peroxidation, and Oxidative Damage of Arsenic in Rat.

    Science.gov (United States)

    Sepand, Mohammad Reza; Razavi-Azarkhiavi, Kamal; Omidi, Ameneh; Zirak, Mohammad Reza; Sabzevari, Samin; Kazemi, Ali Reza; Sabzevari, Omid

    2016-05-01

    Arsenic (As) is a widespread environmental contaminant present around the world in both organic and inorganic forms. Oxidative stress is postulated as the main mechanism for As-induced toxicity. This study was planned to examine the protective effect of acetyl-L-carnitine (ALC) on As-induced oxidative damage in male rats. Animals were randomly divided into four groups of control (saline), sodium arsenite (NaAsO2, 20 mg/kg), ALC (300 mg/kg), and NaAsO2 plus ALC. Animals were dosed orally for 28 successive days. Blood and tissue samples including kidney, brain, liver, heart, and lung were collected on the 28th day and evaluated for oxidative damage and histological changes. NaAsO2 exposure caused a significant lipid peroxidation as evidenced by elevation in thiobarbituric acid-reactive substances (TBARS). The activity of antioxidant enzymes such as glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), as well as sulfhydryl group content (SH group) was significantly suppressed in various organs following NaAsO2 treatment (P < 0.05). Furthermore, NaAsO2 administration increased serum values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and bilirubin. Our findings revealed that co-administration of ALC and NaAsO2 significantly suppressed the oxidative damage induced by NaAsO2. Tissue histological studies have confirmed the biochemical findings and provided evidence for the beneficial role of ALC. The results concluded that ALC attenuated NaAsO2-induced toxicity, and this protective effect may result from the ability of ALC in maintaining oxidant-antioxidant balance.

  3. Heavy Metal-Induced Oxidative DNA Damage in Earthworms: A Review

    Directory of Open Access Journals (Sweden)

    Takeshi Hirano

    2010-01-01

    Full Text Available Earthworms can be used as a bio-indicator of metal contamination in soil, Earlier reports claimed the bioaccumulation of heavy metals in earthworm tissues, while the metal-induced mutagenicity reared in contaminated soils for long duration. But we examined the metal-induced mutagenicity in earthworms reared in metal containing culture beddings. In this experiment we observed the generation of 8-oxoguanine (8-oxo-Gua in earthworms exposed to cadmium and nickel in soil. 8-oxo-Gua is a major premutagenic form of oxidative DNA damage that induces GC-to-TA point mutations, leading to carcinogenesis.

  4. [Action mechanism of electroacupuncture at stomach meridian acupoints for oxidative damage in rats with gastric ulcer].

    Science.gov (United States)

    Yang, Zongbao; Wang, Yadong; Liu, Qiong; Liu, Mi; Chen, Huijuan; Chang, Xiaorong

    2016-06-12

    To observe the effects of electroacupuncture (EA) at stomach meridian acupoints on expression of oxidation damage factors in serum and gastric mucosal cells in rats with gastric ulcer, and to explore the mechanism of EA at stomach meridian acupoints for oxidative damage in rats with gastric ulcer. Forty clean-grade SD rats were randomly divided into a normal group, a model group, a stomach meridian group and a gallbladder meridian group, ten rats in each one. Except the normal group, rats in the remaining groups were applied the restraint-cold stress method to establish the model of gastric ulcer. Rats in the normal group and model group received no treatment; rats in the stomach meridian group were treated with EA at "Liangmen" (ST 21) and "Zusanli" (ST 36); rats in the gallbladder meridian group were treated with EA at "Riyue" (GB 24) and "Yanglingquan" (GB 34). The EA was given for 30 min, once a day for 7 days totally. The change of gastric mucosal morphology was observed by routine light microscope; enzyme linked immunosorbent assay was used to detect the expressions of malondialdehyde (MDA), glutathione peroxidase (GSH-px) and tumor necrosis factor-α (TNF-α), interleukin-2(IL-2), interleukin-6(IL-6) in serum and gastric mucosal cells of rats. After treatment, compared with the model group, the gastric mucosal damage index was decreased in the stomach meridian group and gallbladder meridian group (both P stomach meridian group (all P stomach meridian group rats ( P stomach meridian acupoints is likely to inhibit the expressions of oxidative damage factors to promote the repair of gastric mucosal injury, which indicates the correlation between meridians and zang-fu .

  5. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    Science.gov (United States)

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. 8-Hydroxy-2'-deoxyguanosine (8-OH-dG): A biomarker of oxidative damage in yellow bullheads chronically exposed to low-level radiation

    International Nuclear Information System (INIS)

    McCreedy, C.D.; Glickman, L.T.

    1995-01-01

    8-hydroxy-2'-deoxyguanosine (8-OH-dG), an oxidation product of the nucleotide deoxyguanosine (dG) was used as a biomarker to assess oxidative damage in brain and gill tissues of yellow bullhead catfish (Ameiurus natalis; n = 18) inhabiting an abandoned reactor reservoir contaminated with low levels of d137 Cs (Pond B, Savannah River Site, SC). DNA was isolated by chloroform-isoamyl extraction, enzymatically digested with Nuclease P1/Calf Intestinal Phosphatase, and analyzed by HPLC with electrochemical detection.Length, weight, age, condition and muscle 137 Cs activity of each fish were also determined. Concentrations of 8-OH-dG were greater in brain than in gill tissues. 8-OH-dG in gill tissues decreased as condition of fish increased, but as age increased, the effect of condition declined. Brain 8-OH-dG concentration was not related to age or condition of fish, but was greater in females and the interaction between gender and 137 Cs was significant. Brain 8-OH-dG was positively associated with muscle 137 Cs concentration among females, but was unrelated to 137 Cs concentration in males. At lower 137 Cs concentrations, females tended to have fewer oxidative DNA adducts in brian than did males. Deposition of somatic lipids into eggs may provide females some anti-oxidant benefit by diminishing the contribution of lipid peroxidation to DNA damage. 8-OH-dG is a sensitive biomarker of low-level radiation exposure, however, its application in fish requires consideration of factors such as gender, age, body-condition, and the tissue type sampled

  7. Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans

    International Nuclear Information System (INIS)

    Park, Yoo Kyoung; Park, Eunju; Kim, Jung-Shin; Kang, Myung-Hee

    2003-01-01

    Grape contains flavonoids with antioxidant properties which are believed to be protective against various types of cancer. This antioxidative protection is possibly provided by the effective scavenging of reactive oxygen species (ROS), thus defending cellular DNA from oxidative damage and potential mutations. This study of healthy adults tested whether a daily regimen of grape juice supplementation could reduce cellular DNA damage in peripheral lymphocytes and reduce the amount of free radicals released. Sixty-seven healthy volunteers (16 women and 51 men) aged 19-57 years were given 480 ml of grape juice daily for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length (TL). Levels of free radicals were determined by reading the lucigenin-perborate ROS generating source, using the Ultra-Weak Chemiluminescence Analyzer System. Grape juice consumption resulted in a significant decrease in lymphocyte DNA damage expressed by TL (before supplementation: 88.75±1.55 μm versus after supplementation: 70.25±1.31 μm; P=0.000 by paired t-test). Additionally, grape juice consumption for 8 weeks reduced the ROS/photon count by 15%, compared to the beginning of the study. The preventive effect of grape juice against DNA damage was simultaneously shown in both sexes. These results indicate that the consumption of grape juice may increase plasma antioxidant capacity, resulting in reduced DNA damage in peripheral lymphocytes achieved at least partially by a reduced release of ROS. Our findings support the hypothesis that polyphenolic compounds contained in grape juice exert cancer-protective effects on lymphocytes, limiting oxidative DNA damage possibly via a decrease in free radical levels

  8. Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yoo Kyoung; Park, Eunju; Kim, Jung-Shin; Kang, Myung-Hee

    2003-08-28

    Grape contains flavonoids with antioxidant properties which are believed to be protective against various types of cancer. This antioxidative protection is possibly provided by the effective scavenging of reactive oxygen species (ROS), thus defending cellular DNA from oxidative damage and potential mutations. This study of healthy adults tested whether a daily regimen of grape juice supplementation could reduce cellular DNA damage in peripheral lymphocytes and reduce the amount of free radicals released. Sixty-seven healthy volunteers (16 women and 51 men) aged 19-57 years were given 480 ml of grape juice daily for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length (TL). Levels of free radicals were determined by reading the lucigenin-perborate ROS generating source, using the Ultra-Weak Chemiluminescence Analyzer System. Grape juice consumption resulted in a significant decrease in lymphocyte DNA damage expressed by TL (before supplementation: 88.75{+-}1.55 {mu}m versus after supplementation: 70.25{+-}1.31 {mu}m; P=0.000 by paired t-test). Additionally, grape juice consumption for 8 weeks reduced the ROS/photon count by 15%, compared to the beginning of the study. The preventive effect of grape juice against DNA damage was simultaneously shown in both sexes. These results indicate that the consumption of grape juice may increase plasma antioxidant capacity, resulting in reduced DNA damage in peripheral lymphocytes achieved at least partially by a reduced release of ROS. Our findings support the hypothesis that polyphenolic compounds contained in grape juice exert cancer-protective effects on lymphocytes, limiting oxidative DNA damage possibly via a decrease in free radical levels.

  9. 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

    Directory of Open Access Journals (Sweden)

    C. Ruth Archer

    2015-12-01

    Full Text Available 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.

  10. Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and Combats Hyperglycaemia in Diabetic Rats.

    Science.gov (United States)

    Suresh, Sithara; Waly, Mostafa Ibrahim; Rahman, Mohammad Shafiur; Guizani, Nejib; Al-Kindi, Mohamed Abdullah Badar; Al-Issaei, Halima Khalfan Ahmed; Al-Maskari, Sultan Nasser Mohd; Al-Ruqaishi, Bader Rashid Said; Al-Salami, Ahmed

    2017-12-01

    Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli ( Brassica oleracea ) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats. Streptozotocin (STZ) drug was used as a diabetogenic agent in a single intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level for each rat was measured twice a week. After 8 weeks, all animals were fasted overnight and sacrificed; pancreatic tissues were homogenized and used for measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and total antioxidant capacity (TAC) as well as histopathological examination for pancreatic tissues was examined. Diabetic rats showed significantly higher levels of DNA damage, GSH depletion, and impaired TAC levels in comparison to non-diabetics ( P <0.05). The treatment of diabetic rats with BE significantly reduced DNA damage and conserved GSH and TAC values ( P <0.01). BE attenuated pancreatic histopathological changes in diabetic rats. The results of this study indicated that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as an anti-diabetic herbal medicine and provided insights into the capacity of BE to be used for phytoremediation purposes for human type 2 diabetes.

  11. Attenuating brain inflammation, ischemia, and oxidative damage by hyperbaric oxygen in diabetic rats after heat stroke

    Directory of Open Access Journals (Sweden)

    Kai-Li Lee

    2013-08-01

    Conclusion: Our results suggest that, in diabetic animals, HBO2 therapy may improve outcomes of HS in part by reducing heat-induced activated inflammation and ischemic and oxidative damage in the hypothalamus and other brain regions.

  12. Hydrogen sulfide oxidation without oxygen - oxidation products and pathways

    International Nuclear Information System (INIS)

    Fossing, H.

    1992-01-01

    Hydrogen sulfide oxidation was studied in anoxic marine sediments-both in undisturbed sediment cores and in sediment slurries. The turn over of hydrogen sulfide was followed using 35 S-radiolabeled hydrogen sulfide which was injected into the sediment. However, isotope exchange reactions between the reduced sulfur compounds, in particular between elemental sulfur and hydrogen sulfide, influenced on the specific radioactivity of these pools. It was, therefore, not possible to measure the turn over rates of the reduced sulfur pools by the radiotracer technique but merely to use the radioisotope to demonstrate some of the oxidation products. Thiosulfate was one important intermediate in the anoxic oxidation of hydrogen sulfide and was continuously turned over by reduction, oxidation and disproportionation. The author discusses the importance of isotope exchange and also presents the results from experiments in which both 35 S-radiolabeled elemental sulfur, radiolabeled hydrogen sulfide and radiolabeled thiosulfate were used to study the intermediates in the oxidative pathways of the sulfur cycle

  13. Lycopene and ß-carotene protect in vivo iron-induced oxidative stress damage in rat prostate

    Directory of Open Access Journals (Sweden)

    H.R. Matos

    2006-02-01

    Full Text Available It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip ferric nitrilotriacetate (Fe-NTA (10 mg Fe/kg. Plasma ß-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg-1 day-1 ß-carotene or lycopene in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or ß-carotene, respectively. After 5 days of carotenoid treatment, lycopene and ß-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 ± 0.6 residues/10(6 dGuo 3 h after Fe-NTA injection compared with control rats (1.7 ± 0.3 residues/10(6 dGuo. Rats supplemented with lycopene or ß-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70% in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78% increase in malondialdehyde accumulation. Lycopene or ß-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.

  14. Early life hormetic treatments decrease irradiation-induced oxidative damage, increase longevity, and enhance sexual performance during old age in the Caribbean fruit fly

    International Nuclear Information System (INIS)

    López-Martínez, Giancarlo; Hahn, Daniel A.

    2014-01-01

    Early life events can have dramatic consequences on performance later in life. Exposure to stressors at a young age affects development, the rate of aging, risk of disease, and overall lifespan. In spite of this, mild stress exposure early in life can have beneficial effects on performance later in life. These positive effects of mild stress are referred to as physiological conditioning hormesis. In our current study we used anoxia conditioning hormesis as a pretreatment to reduce oxidative stress and improve organismal performance, lifespan, and healthspan of Caribbean fruit flies. We used gamma irradiation to induce mild oxidative damage in a low-dose experiment, and massive oxidative damage in a separate high-dose experiment, in pharate adult fruit flies just prior to adult emergence. Irradiation-induced oxidative stress leads to reduced adult emergence, flight ability, mating performance, and lifespan. We used a hormetic approach, one hour of exposure to anoxia plus irradiation in anoxia, to lower post-irradiation oxidative damage. We have previously shown that this anoxic-conditioning treatment elevates total antioxidant capacity and lowers post-irradiation oxidative damage to lipids and proteins. In this study, conditioned flies had lower mortality rates and longer lifespan compared to those irradiated without hormetic conditioning. As a metric of healthspan, we tracked mating both at a young age (10 d) and old age (30 d). We found that anoxia-conditioned male flies were more competitive at young ages when compared to unconditioned irradiation stressed male flies, and that the positive effects of anoxic conditioning hormesis on mating success were even more pronounced in older males. Our data shows that physiological conditioning hormesis at a young age, not only improves immediate metrics of organismal performance (emergence, flight, mating), but the beneficial effects also carry into old age by reducing late life oxidative damage and improving lifespan and

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

    Science.gov (United States)

    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.

  16. Fission product behavior during the first two PBF severe fuel damage tests

    International Nuclear Information System (INIS)

    Osetek, D.J.; Cronenberg, A.W.; Hobbins, R.R.; Vinjamuri, K.

    1984-01-01

    The results of the first two severe fuel damage tests performed in the Power Burst Facility are assessed in terms of fission product release and chemical behavior. On-line gamma spectroscopy and grab sample data indicate limited release during solid-phase fuel heatup. Analysis indicates that the fuel morphology conditions for the trace-irradiated fuel employed in these two tests limit initial release. Only upon high temperature fuel restructuring and liquefaction is significant release indicated. Chemical equilibrium predictions, based on steam oxidation or reduction conditions, indicate I to be the primary iodine species during trnsport in the steam environment of the first test and CsI to be the primary species during transport in the hydrogen environment of the second test. However, the higher steam flow rate conditions of the first test transported the released iodine through the sample system; whereas, low-hydrogen flow rate of the second test apparently allowed the vast majority of iodine-bearing compounds to plateout during transport

  17. Protective Effects of an Ancient Chinese Kidney-Tonifying Formula against H2O2-Induced Oxidative Damage to MES23.5 Cells.

    Science.gov (United States)

    Xu, Yihui; Lin, Wei; Ye, Shuifen; Wang, Huajin; Wang, Tingting; Su, Youyan; Wu, Liangning; Wang, Yuanwang; Xu, Qian; Xu, Chuanshan; Cai, Jing

    2017-01-01

    Oxidative damage plays a critical role in the etiology of neurodegenerative disorders including Parkinson's disease (PD). In our study, an ancient Chinese kidney-tonifying formula, which consists of Cistanche , Epimedii, and Polygonatum cirrhifolium , was investigated to protect MES23.5 dopaminergic neurons against hydrogen peroxide- (H 2 O 2 -) induced oxidative damage. The damage effects of H 2 O 2 on MES23.5 cells and the protective effects of KTF against oxidative stress were evaluated using MTT assay, transmission electron microscopy (TEM), immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. The results showed that cell viability was dramatically decreased after a 12 h exposure to 150  μ M H 2 O 2 . TEM observation found that the H 2 O 2 -treated MES23.5 cells presented cellular organelle damage. However, when cells were incubated with KTF (3.125, 6.25, and 12.5  μ g/ml) for 24 h after H 2 O 2 exposure, a significant protective effect against H 2 O 2 -induced damage was observed in MES23.5 cells. Using ICC, we found that KTF inhibited the reduction of the tyrosine hydroxylase (TH) induced by H 2 O 2 , upregulated the mRNA and protein expression of HO-1, CAT, and GPx-1, and downregulated the expression of caspase 3. These results indicated that KTF may provide neuron protection against H 2 O 2 -induced cell damage through ameliorating oxidative stress, and our findings provide a new potential strategy for the prevention and treatment of Parkinson's disease.

  18. DNA damage in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Coppedè, Fabio, E-mail: fabio.coppede@med.unipi.it; Migliore, Lucia, E-mail: lucia.migliore@med.unipi.it

    2015-06-15

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  19. DNA damage in neurodegenerative diseases

    International Nuclear Information System (INIS)

    Coppedè, Fabio; Migliore, Lucia

    2015-01-01

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  20. In vitro Repair of Oxidative DNA Damage by Human Nucleotide Excision Repair System: Possible Explanation for Neurodegeneration in Xeroderma Pigmentosum Patients

    Science.gov (United States)

    Reardon, Joyce T.; Bessho, Tadayoshi; Kung, Hsiang Chuan; Bolton, Philip H.; Sancar, Aziz

    1997-08-01

    Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by sunlight and, as a consequence, develop multiple cancers in areas exposed to light. The second most common sign, present in 20-30% of XP patients, is a set of neurological abnormalities caused by neuronal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurodegeneration in XP patients remains unexplained. In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible for removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism.

  1. Electron paramagnetic resonance evidence of hydroxyl radical generation and oxidative damage induced by tetrabromobisphenol A in Carassius auratus

    Energy Technology Data Exchange (ETDEWEB)

    Shi Huahong [State Key Laboratory of Pollution Control and Resource Reuse, Nanjing University, Nanjing 210093 (China)]. E-mail: huahongshi@tom.com; Wang Xiaorong [State Key Laboratory of Pollution Control and Resource Reuse, Nanjing University, Nanjing 210093 (China); Luo Yi [State Key Laboratory of Pollution Control and Resource Reuse, Nanjing University, Nanjing 210093 (China); Su Yan [State Key Laboratory of Pollution Control and Resource Reuse, Nanjing University, Nanjing 210093 (China)

    2005-09-30

    Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants (BFRs). To confirm its putative oxidative stress-inducing activity, freshwater fish Carassius auratus were injected intraperitoneally with TBBPA. One experiment lasted 3 h to 28 days after a single injection of 100 mg/kg TBBPA, and the other lasted 24 h after a single injection of 0-300 mg/kg TBBPA. Reactive oxygen species (ROS) were trapped by phenyl-tert-butyl nitrone (PBN) and detected by electron paramagnetic resonance (EPR). Protein carbonyl (PCO) and lipid peroxidation product (LPO) content were also determined. A six-line EPR spectrum was detected in the sample prepared in air, and a multiple one was obtained in nitrogen. The observed spectrum in nitrogen fits the simulation one with PBN/{center_dot}OCH{sub 3} and PBN/{center_dot}CH{sub 3} quite well. As compared to the control group, TBBPA significantly induced ROS production marked by the intensity of the prominent spectra in liver and bile. TBBPA (100 mg/kg) also significantly increased PCO content in liver starting 24 h and LPO content 3 days after injection. Either PCO or LPO content showed significant relation with ROS production. Based on the hyperfine constants and shape of the spectrum, ROS induced by TBBPA was determined as {center_dot}OH. The results clearly indicated that TBBPA could induce {center_dot}OH generation and result in oxidative damage in liver of C. auratus.

  2. γ-Glutamyl semialdehyde and 2-amino-adipic semialdehyde: biomarkers of oxidative damage to proteins

    DEFF Research Database (Denmark)

    Daneshvar, B.; Frandsen, H.; Autrup, Herman

    1997-01-01

    proteins collected from eight different mammalian species was found to be inversely proportional to their maximum lifespan potential. The content of AAS in plasma proteins of untreated adult rats showed a positive correlation with the age of the rat. In young rats a negative correlation with age was found......Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify...

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

    Science.gov (United States)

    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.

  4. Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells

    Science.gov (United States)

    Song, Jia-Le; Choi, Jung-Ho; Seo, Jae-Hoon; Kil, Jeung-Ha

    2014-01-01

    BACKGROUND/OBJECTIVES This study was performed to investigate the in vitro antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC-PK1 cells. MATERIALS/METHODS 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (•OH), and H2O2 scavenging assay was used to evaluate the in vitro antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were measured. RESULTS The ability of FSeS to scavenge DPPH, •OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly inhibited H2O2-induced (500 µM) oxidative damage in the LLC-PK1 cells compared to FSS and AHSS (P sauces, FSeS also significantly increased cellular CAT, SOD, and GSH-px activities and mRNA expression (P < 0.05). CONCULUSIONS These results from the present study suggest that FSeS is an effective radical scavenger and protects against H2O2-induced oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid peroxidation, and stimulating antioxidant enzyme activity. PMID:24741396

  5. MAP kinase-signaling controls nuclear translocation of tripeptidyl-peptidase II in response to DNA damage and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Preta, Giulio; Klark, Rainier de; Chakraborti, Shankhamala [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden); Glas, Rickard, E-mail: rickard.glas@ki.se [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden)

    2010-08-27

    Research highlights: {yields} Nuclear translocation of TPPII occurs in response to different DNA damage inducers. {yields} Nuclear accumulation of TPPII is linked to ROS and anti-oxidant enzyme levels. {yields} MAPKs control nuclear accumulation of TPPII. {yields} Inhibited nuclear accumulation of TPPII decreases DNA damage-induced {gamma}-H2AX expression. -- Abstract: Reactive oxygen species (ROS) are a continuous hazard in eukaroytic cells by their ability to cause damage to biomolecules, in particular to DNA. Previous data indicated that the cytosolic serine peptidase tripeptidyl-peptidase II (TPPII) translocates into the nucleus of most tumor cell lines in response to {gamma}-irradiation and ROS production; an event that promoted p53 expression as well as caspase-activation. We here observed that nuclear translocation of TPPII was dependent on signaling by MAP kinases, including p38MAPK. Further, this was caused by several types of DNA-damaging drugs, a DNA cross-linker (cisplatinum), an inhibitor of topoisomerase II (etoposide), and to some extent also by nucleoside-analogues (5-fluorouracil, hydroxyurea). In the minority of tumor cell lines where TPPII was not translocated into the nucleus in response to DNA damage we observed reduced intracellular ROS levels, and the expression levels of redox defense systems were increased. Further, treatment with the ROS-inducer {gamma}-hexa-chloro-cyclohexane ({gamma}-HCH, lindane), an inhibitor of GAP junctions, restored nuclear translocation of TPPII in these cell lines upon {gamma}-irradiation. Moreover, blocking nuclear translocation of TPPII in etoposide-treated cells, by using a peptide-derived inhibitor (Z-Gly-Leu-Ala-OH), attenuated expression of {gamma}-H2AX in {gamma}-irradiated melanoma cells. Our results indicated a role for TPPII in MAPK-dependent DNA damage signaling.

  6. Response of Lemna minor L. to short-term cobalt exposure: The effect on photosynthetic electron transport chain and induction of oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Begović, Lidija, E-mail: lbegovic@biologija.unios.hr [Josip Juraj Strossmayer University of Osijek, Department of Biology, Ulica cara Hadrijana 8/A, H R -31000 Osijek (Croatia); Mlinarić, Selma, E-mail: smlinaric@biologija.unios.hr [Josip Juraj Strossmayer University of Osijek, Department of Biology, Ulica cara Hadrijana 8/A, H R -31000 Osijek (Croatia); Antunović Dunić, Jasenka, E-mail: jantunovic@biologija.unios.hr [Josip Juraj Strossmayer University of Osijek, Department of Biology, Ulica cara Hadrijana 8/A, H R -31000 Osijek (Croatia); Katanić, Zorana, E-mail: zkatanic@biologija.unios.hr [Josip Juraj Strossmayer University of Osijek, Department of Biology, Ulica cara Hadrijana 8/A, H R -31000 Osijek (Croatia); Lončarić, Zdenko, E-mail: zdenko.loncaric@pfos.hr [Faculty of Agriculture, Josip Juraj Strossmayer University of Osijek, Ulica kralja Petra Svačića 1d, H R -31000 Osijek (Croatia); Lepeduš, Hrvoje, E-mail: hlepedus@yahoo.com [Faculty of Humanities and Social Sciences, Josip Juraj Strossmayer University of Osijek, Lorenza Jägera 9, HR-31000 Osijek (Croatia); Cesar, Vera, E-mail: vcesarus@yahoo.com [Josip Juraj Strossmayer University of Osijek, Department of Biology, Ulica cara Hadrijana 8/A, H R -31000 Osijek (Croatia)

    2016-06-15

    Highlights: • Cobalt (Co{sup 2+}) impaired the function of oxygen evolving complex (OEC) in L. minor L. • Electron transport through PSII components varied depending on Co{sup 2+} concentration. • K-band was proven to be suitable parameter for investigation of Co{sup 2+} toxicity. • Increased lipid peroxidation level showed early oxidative damage induced by Co{sup 2+}. - Abstract: The effect of two concentrations of cobalt (Co{sup 2+}) on photosynthetic activity and antioxidative response in Lemna minor L. were assessed 24, 48 and 72 h after the start of the exposure. Higher concentration of cobalt (1 mM) induced growth inhibition while lower concentration (0.01 mM) increased photosynthetic pigments content. Analysis of chlorophyll a fluorescence transients revealed high sensitivity of photosystem II primary photochemistry to excess of Co{sup 2+} especially at the higher concentration where decreased electron transport beyond primary quinone acceptor Q{sub A}{sup −} and impaired function of oxygen evolving complex (OEC) was observed. Due to impairment of OEC, oxygen production was decreased at higher Co{sup 2+} concentration. Activity of superoxide dismutase was mainly inhibited while lipid peroxidation increased, at both concentrations, indicating that cobalt-induced oxidative damage after short exposure and moreover, susceptibility of the membranes in the cell to cobalt toxicity. Results obtained in this study suggest possible application of used parameters as tools in assessment of early damage caused by metals.

  7. Radiation-damage recovery in undoped and oxidized Li doped Mg O crystals implanted with lithium ions

    Energy Technology Data Exchange (ETDEWEB)

    Alves, E. E-mail: ealves@itn.pt; Silva, R.C. da; Pinto, J.V.; Monteiro, T.; Savoini, B.; Caceres, D.; Gonzalez, R.; Chen, Y

    2003-05-01

    Undoped MgO and oxidized Li-doped MgO single crystals were implanted with 1 x 10{sup 17} Li{sup +}/cm{sup 2} at 175 keV. The Rutherford backscattering spectrometry (RBS)/channeling data obtained after implantation shows that damage was produced throughout the entire range of the implanted ions. Optical absorption measurements indicate that after implantation the most intense band occurs at {approx}5.0 eV, which has been associated with anion vacancies. After annealing at 450 K the intensity of the oxygen-vacancy band decreases monotonically with temperature and completely disappears at 950 K. A broad extinction band centered at {approx}2.14 eV associated with lithium precipitates emerges gradually and anneals out at 1250 K. RBS/channeling shows that recovery of the implantation damage is completed after annealing the oxidized samples at 1250 K.

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

    Science.gov (United States)

    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

  9. Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects.

    Science.gov (United States)

    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.

  10. Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station.

    Science.gov (United States)

    Zwart, Sara R; Morgan, Jennifer L L; Smith, Scott M

    2013-07-01

    Increases in stored iron and dietary intake of iron during space flight have raised concern about the risk of excess iron and oxidative damage, particularly in bone. The objectives of this study were to perform a comprehensive assessment of iron status in men and women before, during, and after long-duration space flight and to quantify the association of iron status with oxidative damage and bone loss. Fasting blood and 24-h urine samples were collected from 23 crew members before, during, and after missions lasting 50 to 247 d to the International Space Station. Serum ferritin and body iron increased early in flight, and transferrin and transferrin receptors decreased later, which indicated that early increases in body iron stores occurred through the mobilization of iron to storage tissues. Acute phase proteins indicated no evidence of an inflammatory response during flight. Serum ferritin was positively correlated with the oxidative damage markers 8-hydroxy-2'-deoxyguanosine (r = 0.53, P < 0.001) and prostaglandin F2α (r = 0.26, P < 0.001), and the greater the area under the curve for ferritin during flight, the greater the decrease in bone mineral density in the total hip (P = 0.031), trochanter (P = 0.006), hip neck (P = 0.044), and pelvis (P = 0.049) after flight. Increased iron stores may be a risk factor for oxidative damage and bone resorption.

  11. Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids - early effect

    Directory of Open Access Journals (Sweden)

    Makarewicz Jacek

    2010-10-01

    Full Text Available Abstract Introduction Radioiodine (131I therapy is widely accepted as an essential part of therapeutic regimens in many cases of differentiated thyroid cancer. Radiation-induced oxidative damage to macromolecules is a well known phenomenon. Frequently examined process to evaluate oxidative damage to macromolecules is lipid peroxidation (LPO, resulting from oxidative damage to membrane lipids. The aim of the study was to examine serum LPO level in hypothyroid (after total thyroidectomy cancer patients subjected to ablative activities of 131I. Materials and methods The study was carried out in 21 patients (18 females and 3 males, average age 52.4 ± 16.5 years after total thyroidectomy for papillary (17 patients or follicular (4 patients thyroid carcinoma. Hypothyroidism was confirmed by increased TSH blood concentration (BRAHMS, Germany, measured before 131I therapy. Activity of 2.8 - 6.9 GBq of 131I was administered to the patients orally as sodium iodide (OBRI, Poland. Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA, as an index of LPO (LPO-586 kit, Calbiochem, USA, were measured in blood serum just before 131I administration (day "0" and on the days 1-4 after 131I therapy. Sera from 23 euthyroid patients served as controls. Correlations between LPO and TSH or 131I activity were calculated. Results Expectedly, serum LPO level, when measured before 131I therapy, was several times higher (p 131I therapy. LPO did not correlate with TSH concentration. In turn, negative correlation was found between 131I activity and LPO level on the day "2" after radioiodine treatment. Conclusions Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.

  12. Benchmark Theoretical and Experimental Study on N-15 NMR Shifts of Oxidatively Damaged Guanine

    Czech Academy of Sciences Publication Activity Database

    Dračínský, Martin; Šála, Michal; Klepetářová, Blanka; Šebera, Jakub; Fukal, Jiří; Holečková, Veronika; Tanaka, Y.; Nencka, Radim; Sychrovský, Vladimír

    2016-01-01

    Roč. 120, č. 5 (2016), s. 915-925 ISSN 1520-6106 R&D Projects: GA ČR GA13-27676S; GA ČR GA15-11223S Institutional support: RVO:61388963 Keywords : NMR spectroscopy * DFT calculations * oxidatively damaged guanine * hOGG1 Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.177, year: 2016

  13. Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

    Science.gov (United States)

    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 (Pstress 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.

  14. Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

    Directory of Open Access Journals (Sweden)

    Shraddha D. Rege

    2013-01-01

    Full Text Available Resveratrol (3,5,4′-trihydroxy-trans-stilbene is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob mice. Resveratrol was administered orally at the dose of 25 mg kg−1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice.

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

    Science.gov (United States)

    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®

  16. Ursolic Acid-Regulated Energy Metabolism—Reliever or Propeller of Ultraviolet-Induced Oxidative Stress and DNA Damage?

    Directory of Open Access Journals (Sweden)

    Yuan-Hao Lee

    2014-08-01

    Full Text Available Ultraviolet (UV light is a leading cause of diseases, such as skin cancers and cataracts. A main process mediating UV-induced pathogenesis is the production of reactive oxygen species (ROS. Excessive ROS levels induce the formation of DNA adducts (e.g., pyrimidine dimers and result in stalled DNA replication forks. In addition, ROS promotes phosphorylation of tyrosine kinase-coupled hormone receptors and alters downstream energy metabolism. With respect to the risk of UV-induced photocarcinogenesis and photodamage, the antitumoral and antioxidant functions of natural compounds become important for reducing UV-induced adverse effects. One important question in the field is what determines the differential sensitivity of various types of cells to UV light and how exogenous molecules, such as phytochemicals, protect normal cells from UV-inflicted damage while potentiating tumor cell death, presumably via interaction with intracellular target molecules and signaling pathways. Several endogenous molecules have emerged as possible players mediating UV-triggered DNA damage responses. Specifically, UV activates the PIKK (phosphatidylinositol 3-kinase-related kinase family members, which include DNA-PKcs, ATM (ataxia telangiectasia mutated and mTOR (mammalian target of rapamycin, whose signaling can be affected by energy metabolism; however, it remains unclear to what extent the activation of hormone receptors regulates PIKKs and whether this crosstalk occurs in all types of cells in response to UV. This review focuses on proteomic descriptions of the relationships between cellular photosensitivity and the phenotypic expression of the insulin/insulin-like growth receptor. It covers the cAMP-dependent pathways, which have recently been shown to regulate the DNA repair machinery through interactions with the PIKK family members. Finally, this review provides a strategic illustration of how UV-induced mitogenic activity is modulated by the insulin

  17. Oxidative damage induced by heat stress could be relieved by nitric oxide in Trichoderma harzianum LTR-2.

    Science.gov (United States)

    Yu, Yang; Yang, Zijun; Guo, Kai; Li, Zhe; Zhou, Hongzi; Wei, Yanli; Li, Jishun; Zhang, Xinjian; Harvey, Paul; Yang, Hetong

    2015-04-01

    Trichoderma harzianum is an important commercial biocontrol fungal agent. The temperature has been shown to be an important parameter and strain-specific to the mycelia growth of fungi, but less report makes the known of the mechanisms in T. harzianum. In our study, a 6-h treatment of heat increased the thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) concentration in mycelia to 212 and 230 % the level of the control, respectively. The exogenous NO donor sodium nitroprusside (150 μM) reduced the TBARS concentration to 53 % of that under heat stress (HS). At the same time, the NO-specific scavenger at 250 μM, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-1-oxyl-3-oxide, prevented the exogenous NO-relieved TBARS accumulation under HS. The increased NO concentration under HS was reduced 41 % by the NO synthase (NOS) inhibitor L-N(G)-nitroarginine methyl ester, but not the nitrate reductase (NR) inhibitor tungstate. Our study exhibited that NO can protect the mycelia of T. harzianum from HS and reduce the oxidative damage by enhancing the activity of NOS and NR.

  18. Seasonal variability of oxidative stress markers in city bus drivers. Part II. Oxidative damage to lipids and proteins.

    Science.gov (United States)

    Rossner, Pavel; Svecova, Vlasta; Milcova, Alena; Lnenickova, Zdena; Solansky, Ivo; Sram, Radim J

    2008-07-03

    The aim of the present study was to investigate the seasonal variability of markers of oxidative damage to lipids (15-F2t-isoprostane, 15-F2t-IsoP) and proteins (protein carbonyl levels) in 50 bus drivers and 50 controls from Prague, Czech Republic, and to identify factors affecting oxidative stress markers. The samples were collected in three seasons with different levels of air pollution. The exposure to environmental pollutants (carcinogenic polycyclic aromatic hydrocarbons, c-PAHs, particulate matter, PM2.5 and PM10, and volatile organic compounds, VOC) was monitored by personal and/or stationary monitors. For the analysis of both markers, ELISA techniques were used. The median levels of individual markers in bus drivers versus controls were as follows: 15-F2t-IsoP (nmol/mmol creatinine): winter 2005, 0.81 versus 0.68 (pbus drivers in winter seasons, but not in summer. Lipid peroxidation was positively correlated with c-PAHs and PM exposure; protein oxidation correlated negatively and was highest in summer suggesting another factor(s) affecting protein carbonyl levels.

  19. The role of phospholipid oxidation products in inflammatory and autoimmune diseases: evidence from animal models and in humans.

    Science.gov (United States)

    Leitinger, Norbert

    2008-01-01

    Since the discovery of oxidized phospholipids (OxPL) and their implication as modulators of inflammation in cardiovascular disease, roles for these lipid oxidation products have been suggested in many other disease settings. Lipid oxidation products accumulate in inflamed and oxidatively damaged tissue, where they are derived from oxidative modification of lipoproteins, but also from membranes of cells undergoing apoptosis. Thus, increased oxidative stress as well as decreased clearance of apoptotic cells has been implied to contribute to accumulation of OxPL in chronically inflamed tissues.A central role for OxPL in disease states associated with dyslipedemia, including atherosclerosis, diabetes and its complications, metabolic syndrome, and renal insufficiency, as well as general prothrombotic states, has been proposed. In addition, in organs which are constantly exposed to oxidative stress, including lung, skin, and eyes, increased levels of OxPL are suggested to contribute to inflammatory conditions. Moreover, accumulation of OxPL causes general immunmodulation and may lead to autoimmune diseases. Evidence is accumulating that OxPL play a role in lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis. Last but not least, a role for OxPL in neurological disorders including multiple sclerosis (MS), Alzheimer's and Parkinson's disease has been suggested.This chapter will summarize recent findings obtained in animal models and from studies in humans that indicate that formation of OxPL represents a general mechanism that may play a major role in chronic inflammatory and autoimmune diseases.

  20. Temperature experienced during incubation affects antioxidant capacity but not oxidative damage in hatchling red-eared slider turtles (Trachemys scripta elegans).

    Science.gov (United States)

    Treidel, L A; Carter, A W; Bowden, R M

    2016-02-01

    Our understanding of how oxidative stress resistance phenotypes are affected by the developmental environment is limited. One component of the developmental environment, which is likely central to early life oxidative stress among ectothermic and oviparous species, is that of temperature. We investigated how incubation temperature manipulations affect oxidative damage and total antioxidant capacity (TAC) in red-eared slider turtle (Trachemys scripta elegans) hatchlings. First, to determine whether temperature fluctuations elicit oxidative stress, eggs from clutches were randomly assigned to either a constant (29.5 °C) or daily fluctuating temperature incubation (28.7 ± 3 °C) treatment. Second, to assess the effect of temperature fluctuation frequency on oxidative stress, eggs were incubated in one of three fluctuating incubation regimes: 28.7 ± 3 °C fluctuations every 12 h (hyper), 24 h (normal) or 48 h (hypo). Third, we tested the influence of average incubation temperature by incubating eggs in a daily fluctuating incubation temperature regime with a mean temperature of 26.5 °C (low), 27.1 °C (medium) or 27.7 °C (high). Although the accumulation of oxidative damage in hatchlings was unaffected by any thermal manipulation, TAC was affected by both temperature fluctuation frequency and average incubation temperature. Individuals incubated with a low frequency of temperature fluctuations had reduced TAC, while incubation at a lower average temperature was associated with enhanced TAC. These results indicate that although sufficient to prevent oxidative damage, TAC is influenced by developmental thermal environments, potentially because of temperature-mediated changes in metabolic rate. The observed differences in TAC may have important future consequences for hatchling fitness and overwinter survival. © 2016. Published by The Company of Biologists Ltd.

  1. Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans

    DEFF Research Database (Denmark)

    Møller, P; Loft, S; Lundby, C

    2001-01-01

    ; lymphocytes were isolated for analysis of DNA strand breaks and oxidatively altered nucleotides, detected by endonuclease III and formamidipyridine glycosylase (FPG) enzymes. Urine was collected for 24 h periods for analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage...... oxygen species, generated by leakage of the mitochondrial respiration or during a hypoxia-induced inflammation. Furthermore, the presence of DNA strand breaks may play an important role in maintaining hypoxia-induced inflammation processes. Hypoxia seems to deplete the antioxidant system of its capacity...

  2. Effect of Oxidative Damage on the Stability and Dimerization of Superoxide Dismutase 1

    OpenAIRE

    Petrov, Drazen; Daura, Xavier; Zagrovic, Bojan

    2016-01-01

    During their life cycle, proteins are subject to different modifications involving reactive oxygen species. Such oxidative damage to proteins may lead to the formation of insoluble aggregates and cytotoxicity and is associated with age-related disorders including neurodegenerative diseases, cancer, and diabetes. Superoxide dismutase 1 (SOD1), a key antioxidant enzyme in human cells, is particularly susceptible to such modifications. Moreover, this homodimeric metalloenzyme has been directly l...

  3. Contribution Of Brain Tissue Oxidative Damage In Hypothyroidism-associated Learning and Memory Impairments

    Directory of Open Access Journals (Sweden)

    Yousef Baghcheghi

    2017-01-01

    Full Text Available The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments.

  4. Oxidative DNA damage and mammary cell proliferation by alcohol-derived salsolinol.

    Science.gov (United States)

    Murata, Mariko; Midorikawa, Kaoru; Kawanishi, Shosuke

    2013-10-21

    Drinking alcohol is a risk factor for breast cancer. Salsolinol (SAL) is endogenously formed by a condensation reaction of dopamine with acetaldehyde, a major ethanol metabolite, and SAL is detected in blood and urine after alcohol intake. We investigated the possibility that SAL can participate in tumor initiation and promotion by causing DNA damage and cell proliferation, leading to alcohol-associated mammary carcinogenesis. SAL caused oxidative DNA damage including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in the presence of transition metal ions, such as Cu(II) and Fe(III)EDTA. Inhibitory effects of scavengers on SAL-induced DNA damage and the electron spin resonance study indicated the involvement of H₂O₂, which is generated via the SAL radical. Experiments on scavengers and site specificity of DNA damage suggested ·OH generation via a Fenton reaction and copper-peroxide complexes in the presence of Fe(III)EDTA and Cu(II), respectively. SAL significantly increased 8-oxodG formation in normal mammary epithelial MCF-10A cells. In addition, SAL induced cell proliferation in estrogen receptor (ER)-negative MCF-10A cells, and the proliferation was inhibited by an antioxidant N-acetylcysteine and an epidermal growth factor receptor (EGFR) inhibitor AG1478, suggesting that reactive oxygen species may participate in the proliferation of MCF-10A cells via EGFR activation. Furthermore, SAL induced proliferation in estrogen-sensitive breast cancer MCF-7 cells, and a surface plasmon resonance sensor revealed that SAL significantly increased the binding activity of ERα to the estrogen response element but not ERβ. In conclusion, SAL-induced DNA damage and cell proliferation may play a role in tumor initiation and promotion of multistage mammary carcinogenesis in relation to drinking alcohol.

  5. Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine

    Science.gov (United States)

    Ahmad, Mir Kaisar; Khan, Aijaz Ahmed; Ali, Shaikh Nisar; Mahmood, Riaz

    2015-01-01

    Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the activities of intestinal brush border membrane enzymes while those of antioxidant defence and carbohydrate metabolism were also severely altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive intestinal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine+ KBrO3 group. These results show that taurine ameliorates bromate induced tissue toxicity and oxidative damage by improving the antioxidant defence, tissue integrity and energy metabolism. Taurine can, therefore, be potentially used as a therapeutic/protective agent against toxicity of KBrO3 and related compounds. PMID:25748174

  6. Clovamide-rich extract from Trifolium pallidum reduces oxidative stress-induced damage to blood platelets and plasma.

    Science.gov (United States)

    Kolodziejczyk, Joanna; Olas, Beata; Wachowicz, Barbara; Szajwaj, Barbara; Stochmal, Anna; Oleszek, Wieslaw

    2011-09-01

    Numerous plants (including clovers) have been widely used in folk medicine for the treatment of different disorders. This in vitro study was designed to examine the antioxidative effects of the clovamide-rich fraction, obtained from aerial parts of Trifolium pallidum, in the protection of blood platelets and plasma against the nitrative and oxidative damage, caused by peroxynitrite (ONOO(-)). Carbonyl groups and 3-nitrotyrosine in blood platelet and plasma proteins were determined by ELISA tests. Thiol groups level was estimated by using 5,5'-dithio-bis(2-nitro-benzoic acid, DTNB). Plasma lipid peroxidation was measured spectrophotometrically as the production of thiobarbituric acid reactive substances. The results from our work indicate that clovamide-rich T. pallidum extract may reveal the protective properties in the prevention against oxidative stress. The presence of clovamide-rich T. pallidum extract (12.5-100 μg/ml) partly inhibited ONOO(-)-mediated protein carbonylation and nitration. All the used concentrations of T. pallidum extract reduced lipid peroxidation in plasma. The antioxidative action of the tested extract in the protection of blood platelet lipids was less effective; the extract at the lowest final concentration (12.5 μg/ml) had no protective effect against lipid peroxidation. The present results indicate that the extract from T. pallidum is likely to be a source of compounds with the antioxidative properties, useful in the prevention against the oxidative stress-related diseases.

  7. Is the Oxidative DNA Damage Level of Human Lymphocyte Correlated with the Antioxidant Capacity of Serum or the Base Excision Repair Activity of Lymphocyte?

    Directory of Open Access Journals (Sweden)

    Yi-Chih Tsai

    2013-01-01

    Full Text Available A random screening of human blood samples from 24 individuals of nonsmoker was conducted to examine the correlation between the oxidative DNA damage level of lymphocytes and the antioxidant capacity of serum or the base excision repair (BER activity of lymphocytes. The oxidative DNA damage level was measured with comet assay containing Fpg/Endo III cleavage, and the BER activity was estimated with a modified comet assay including nuclear extract of lymphocytes for enzymatic cleavage. Antioxidant capacity was determined with trolox equivalent antioxidant capacity assay. We found that though the endogenous DNA oxidation levels varied among the individuals, each individual level appeared to be steady for at least 1 month. Our results indicate that the oxidative DNA damage level is insignificantly or weakly correlated with antioxidant capacity or BER activity, respectively. However, lymphocytes from carriers of Helicobacter pylori (HP or Hepatitis B virus (HBV tend to give higher levels of oxidative DNA damage (P<0.05. Though sera of this group of individuals show no particular tendency with reduced antioxidant capacity, the respective BER activities of lymphocytes are lower in average (P<0.05. Thus, reduction of repair activity may be associated with the genotoxic effect of HP or HBV infection.

  8. 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.

    Science.gov (United States)

    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

  9. A possible mechanism for transpupillary thermotherapy: nitric-oxide-related cellular damage.

    Science.gov (United States)

    Ozdek, Sengul; Urgancioglu, Berrak; Turkcu, Ummuhani Ozel; Bilgihan, Ayse

    2007-08-01

    To determine the oxidative stress markers on rabbit vitreous following transpupillary thermotherapy (TTT) application. The pigmented rabbit eyes were divided into 3 groups, each containing 6 eyes. Group 1 was used as a control group. Twelve eyes underwent TTT with a power of 250 mW (group 2) and 800 mW (group 3), with a diameter of 3000 microm and duration of 60 s; 24 h after laser application, vitreous samples were collected. Nitric oxide (NO) and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were determined in all groups. NO levels were statistically significantly higher in all groups when compared with the control group (p 0.05). Our results support the hypothesis that TTT application induces NO synthesis, which may lead to occlusion at choroidal neovessels. Because of the nonsignificantly increased levels of MDA and decrease of SOD activities there maybe only a weak relation between lipid peroxidation induced by free oxygen radicals and TTT-induced vascular damage.

  10. Zinc Supplementation against Eimeria acervulina-Induced Oxidative Damage in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Nedyalka V. Georgieva

    2011-01-01

    Full Text Available This study was undertaken to determine the dietary supplements of Zn containing diet on the antioxidant status in chickens experimentally infected with Eimeria acervulina. The antioxidant status was monitored via determination of MDA concentrations and erythrocyte SOD and CAT activities, as well as vitamin E, vitamin C, Cu, and Zn in liver, muscle, and serum. The results showed increased MDA (<.05, CAT (<.001, and decreased SOD (<.001 in the infected birds. Significant changes in Cu and Zn concentrations and dramatically reduction of vitamin C and E concentrations in the infected chickens were found. The observed deviations in the studied enzymes and nonenzymatic parameters evidence the occurrence of oxidative stress following the infection and impaired antioxidant status of chickens, infected with Eimeria acervulina. Our results proved the ameliorating role of CuZn(OH3Cl (0.170 g per kg food against Eimeria acervulina-induced oxidative damage in infected chickens.

  11. Volatile profile, lipid oxidation and protein oxidation of irradiated ready-to-eat cured turkey meat products

    International Nuclear Information System (INIS)

    Feng, Xi; Ahn, Dong Uk

    2016-01-01

    Irradiation had little effects on the thiobarbituric acid reactive substances (TBARS) values in ready-to-eat (RTE) turkey meat products, while it increased protein oxidation at 4.5 kGy. The volatile profile analyses indicated that the amount of sulfur compounds increased linearly as doses increased in RTE turkey meat products. By correlation analysis, a positive correlation was found between benzene/ benzene derivatives and alcohols with lipid oxidation, while aldehydes, ketones and alkane, alkenes and alkynes were positively correlated with protein oxidation. Principle component analysis showed that irradiated meat samples can be discriminated by two categories of volatile compounds: Strecker degradation products and radiolytic degradation products. The cluster analysis of volatile data demonstrated that low-dose irradiation had minor effects on the volatile profile of turkey sausages (<1.5 kGy). However, as the doses increased, the differences between the irradiated and non-irradiated cured turkey products became significant. - Highlights: • Irradiation had little effects on lipid oxidation of ready-to-eat cured turkey. • 4.5 kGy irradiation increased protein oxidation. • Irradiated samples were isolated due to Strecker/radiolytic degradation products. • 1.5 kGy irradiation had limited effects on the volatile profile of turkey sausages. • Dimethyl disulfide can be used as a potential marker for irradiated meat products.

  12. The Effect of Green Tea and Sour Tea (Hibiscus sabdariffa L.) Supplementation on Oxidative Stress and Muscle Damage in Athletes.

    Science.gov (United States)

    Hadi, Amir; Pourmasoumi, Makan; Kafeshani, Marzieh; Karimian, Jahangir; Maracy, Mohammad Reza; Entezari, Mohammad Hasan

    2017-05-04

    Additional oxygen consumption during intense exercises may lead to oxidative stress and contribute to muscular fatigue. Green tea and sour tea (Hibiscus sabdariffa L.), which contain various flavonoids and polyphenols, have many healthful properties such as anticarcinogenic, anti-inflammatory, and heart protecting effects. The aim of the present study was to assess the effects of green tea and sour tea supplementation on oxidative stress and muscle damage in soccer athletes. This randomized, double-blind control trial was conducted on 54 male soccer players. Participants were randomly assigned to three groups to receive: 450 mg/d green tea extract (GTE) in the first group (n = 18), 450 mg/d sour tea extract (STE) in the second group (n = 18) and 450 mg/d maltodextrin in the control group (n = 18). Fasting whole blood samples were taken under resting conditions at the beginning and the end of the study to quantify the serum levels of muscle damage indices, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and oxidative stress biomarkers, malondialdehyde (MDA), and total antioxidant capacity (TAC). After six weeks intervention, athletes who received GTE and STE supplements compared with the placebo had a significantly decreased MDA level (P = 0.008). Furthermore, STE supplementation resulted in a significant increase in TAC level compared with GTE and placebo groups (P = 0.01). However, supplementation with GTE and STE had no significant effects on muscle damage indices. GTE and STE supplementation have beneficial effects on oxidative stress status in male athletes. However, both kinds of tea extract did not affect muscle damage status.

  13. Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo.

    Science.gov (United States)

    Chen, Chiu-Lan; Chi, Chin-Wen; Liu, Tsung-Yun

    2002-02-01

    Chewing areca quid (AQ) has been implicated as a major risk factor for the development of oral squamous-cell carcinoma (OSCC). Recent studies have suggested that AQ-generated reactive oxygen species (ROS) is one of the contributing factors for oral carcinogenesis. However, the AQ used in Taiwan is different from that used in other countries. This study is designed to test whether ROS are generated and the consequent effects in locally prepared AQ in vivo. We measured the hydroxyl radical formation, as represented by the presence of o- and m-tyrosine in saliva from volunteers who chewed AQ containing 20 mg phenylalanine. Their saliva contained significantly higher amounts (p betel leaf. We further tested the oxidative DNA damaging effect of the reconstituted AQ, as evidenced by the elevation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, in hamster buccal pouch. Following daily painting for 14 d, the 8-OH-dG level in hamster buccal pouch is significantly elevated (p < .05) in the AQ-treated group versus the controls. These findings demonstrate that ROS, such as hydroxyl radical, are formed in the human oral cavity during AQ chewing, and chewing such prepared AQ might cause oxidative DNA damage to the surrounding tissues.

  14. Effects of melatonin on spinal cord injury-induced oxidative damage in mice testis.

    Science.gov (United States)

    Yuan, X-C; Wang, P; Li, H-W; Wu, Q-B; Zhang, X-Y; Li, B-W; Xiu, R-J

    2017-09-01

    This study evaluated the effects of melatonin on spinal cord injury (SCI)-induced oxidative damage in testes. Adult male C57BL/6 mice were randomly divided into sham-, SCI- or melatonin (10 mg/kg, i.p.)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a contusion injury at T10 was used. After 1 week, testicular blood flow velocity was measured using the Laser Doppler Line Scanner. Malondialdehyde (MDA), glutathione (GSH), oxidised glutathione (GSSG) and myeloperoxidase (MPO) were measured in testis homogenates. Microvascular permeability of the testes to Evan's Blue was examined by spectrophotometric and fluorescence microscopic quantitation. The tight junction protein zonula occludens-1 (ZO-1) and occludin in testes were assessed by immunoblot analysis. Melatonin increased the reduced blood flow and decreased SCI-induced permeability of capillaries. MDA levels and MPO activity were elevated in the SCI group compared with shams, which was reversed by melatonin. In contrast, SCI-induced reductions in GSH/GSSG ratio were restored by melatonin. Decreased expression of ZO-1 and occludin was observed, which was attenuated by melatonin. Overall, melatonin treatment protects the testes against oxidative stress damage caused by SCI. © 2016 Blackwell Verlag GmbH.

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

    KAUST Repository

    Caputo, Fanny

    2015-08-20

    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. © The Royal Society of Chemistry 2015.

  16. Oxidation kinetics of reaction products formed in uranium metal corrosion.

    Energy Technology Data Exchange (ETDEWEB)

    Totemeier, T. C.

    1998-04-22

    The oxidation behavior of uranium metal ZPPR fuel corrosion products in environments of Ar-4%O{sub 2} and Ar-20%O{sub 2} were studied using thermo-gravimetric analysis (TGA). These tests were performed to extend earlier work in this area specifically, to assess plate-to-plate variations in corrosion product properties and the effect of oxygen concentration on oxidation behavior. The corrosion products from two relatively severely corroded plates were similar, while the products from a relatively intact plate were not reactive. Oxygen concentration strongly affected the burning rate of reactive products, but had little effect on low-temperature oxidation rates.

  17. Oxidation kinetics of reaction products formed in uranium metal corrosion

    International Nuclear Information System (INIS)

    Totemeier, T. C.

    1998-01-01

    The oxidation behavior of uranium metal ZPPR fuel corrosion products in environments of Ar-4%O 2 and Ar-20%O 2 were studied using thermo-gravimetric analysis (TGA). These tests were performed to extend earlier work in this area specifically, to assess plate-to-plate variations in corrosion product properties and the effect of oxygen concentration on oxidation behavior. The corrosion products from two relatively severely corroded plates were similar, while the products from a relatively intact plate were not reactive. Oxygen concentration strongly affected the burning rate of reactive products, but had little effect on low-temperature oxidation rates

  18. 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

    Science.gov (United States)

    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

  19. Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

    Science.gov (United States)

    Said, T; Dutot, M; Martin, C; Beaudeux, J-L; Boucher, C; Enee, E; Baudouin, C; Warnet, J-M; Rat, P

    2007-03-01

    The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

  20. An anthocyanin-rich strawberry extract protects against oxidative stress damage and improves mitochondrial functionality in human dermal fibroblasts exposed to an oxidizing agent.

    Science.gov (United States)

    Giampieri, Francesca; Alvarez-Suarez, José M; Mazzoni, Luca; Forbes-Hernandez, Tamara Y; Gasparrini, Massimiliano; Gonzàlez-Paramàs, Ana M; Santos-Buelga, Celestino; Quiles, Josè L; Bompadre, Stefano; Mezzetti, Bruno; Battino, Maurizio

    2014-08-01

    This study investigates the protective effect of the Sveva strawberry polyphenol-rich extract on human dermal fibroblasts against AAPH-induced oxidative stress. The HPLC-DAD/ESI-MS analysis was used for evaluating the phenolic composition of the fruits. Sveva strawberry presented a high anthocyanin content (639.79 mg per kg fresh fruit), representing ∼86.08% of the total phenolic content, with Pg-3-glc as the most abundant representative (611.18 mg per kg fresh fruit). Only one ellagitannin (agrimoniin) was identified, while two quercetins, three kaempherol derivates, and three ellagic acid derivatives were detected and quantified. Strawberry pre-treatment (0.5 mg ml(-1)) markedly increased human dermal fibroblast viability, with a significant reduction of apoptotic and dead cells, and suppressed AAPH-induced ROS generation, after only 30 minutes of incubation with the oxidizing agent, and lipid peroxidation, against a range of AAPH concentrations tested. Notably, the strawberry extract also improved the mitochondrial functionality: the basal respiratory performance after treatment was ∼1.59-fold higher compared to control cells, while pre-treatment with strawberry extract before oxidative damage increased ∼2.70-fold compared to stressed cells. Our results confirm that the strawberry possesses antioxidant properties, and may be useful for the prevention of free radical-induced skin damage.

  1. 40 CFR 415.50 - Applicability; description of the calcium oxide production subcategory.

    Science.gov (United States)

    2010-07-01

    ... calcium oxide production subcategory. 415.50 Section 415.50 Protection of Environment ENVIRONMENTAL... SOURCE CATEGORY Calcium Oxide Production Subcategory § 415.50 Applicability; description of the calcium... the production of calcium oxide. ...

  2. The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

    Science.gov (United States)

    Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

    2008-10-01

    To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

  3. An Investigation of Damage Factors in Industrial Scale of Light-Weight Bricks Production

    Directory of Open Access Journals (Sweden)

    Dwi Wulandari Kiki

    2017-01-01

    Full Text Available A damage case of light weight brick’s production approximately at 6-7% of total production was found daily in one industry in East Jawa, Indonesia. The physical damage of product always occured. This paper investigates some factors that affect the lost in laboratory analysis. The analysis includes the chemical analysis of raw materials, reactivity of pozzolanic materials, and observation of strength based upon the position of light-weight bricks during autoclaving process. In addition, fly ash is introduced as mineral additive as one of the alternatives to improve the product’s quality. It is also concluded that grinding the silica sands particles is the optimum way to improve the quality, but the adding class F of fly ash to five percent in mixture is the most effective solution. Furthermore, maintaining quality of raw materials, curing process, and maintaining the machine will either reduce the product damage that occurred during the fabrication process in industry.

  4. Angiotensin II type 1a receptor-deficient mice develop angiotensin II-induced oxidative stress and DNA damage without blood pressure increase.

    Science.gov (United States)

    Zimnol, Anna; Amann, Kerstin; Mandel, Philipp; Hartmann, Christina; Schupp, Nicole

    2017-12-01

    Hypertensive patients have an increased risk of developing kidney cancer. We have shown in vivo that besides elevating blood pressure, angiotensin II causes DNA damage dose dependently. Here, the role of blood pressure in the formation of DNA damage is studied. Mice lacking one of the two murine angiotensin II type 1 receptor (AT1R) subtypes, AT1aR, were equipped with osmotic minipumps, delivering angiotensin II during 28 days. Parameters of oxidative stress and DNA damage of kidneys and hearts of AT1aR-knockout mice were compared with wild-type (C57BL/6) mice receiving angiotensin II, and additionally, with wild-type mice treated with candesartan, an antagonist of both AT1R subtypes. In wild-type mice, angiotensin II induced hypertension, reduced kidney function, and led to a significant formation of reactive oxygen species (ROS). Furthermore, genomic damage was markedly increased in this group. All these responses to angiotensin II could be attenuated by concurrent administration of candesartan. In AT1aR-deficient mice treated with angiotensin II, systolic pressure was not increased, and renal function was not affected. However, angiotensin II still led to an increase of ROS in kidneys and hearts of these animals. Additionally, genomic damage in the form of double-strand breaks was significantly induced in kidneys of AT1aR-deficient mice. Our results show that angiotensin II induced ROS production and DNA damage even without the presence of AT1aR and independently of blood pressure changes. Copyright © 2017 the American Physiological Society.

  5. Serum Iron and Nitric Oxide Production in Trypanosoma brucei ...

    African Journals Online (AJOL)

    JTEkanem

    reduction in the serum iron status and a modulation of nitric oxide synthase activity of T. brucei infected rats. ... inflammation and tissue damage15. ... The serum iron level was determined ... concentration or of total nitrate and nitrite ... 15. 16. 17. 18. Days. S e ru m iro n lev e l mg. /ml. Infected treated. Infected untreated. 0.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Zhixiu Cao

    Full Text Available 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.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.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.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.

  8. Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage

    International Nuclear Information System (INIS)

    Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J.; Rudich, Yinon

    2016-01-01

    Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. - Highlights: • Repeated exposure to urban PM cause systemic inflammation and oxidative damage to lung tissue lipids and proteins. • Repeated exposure to these PM extracts decreased transcription of Nrf2 protective genes. • Single as opposed to repeated exposure, induced confined lung response accompanied by activated defense mechanisms. • Metals, potentially from break and tire wear, drive the pulmonary response with exposure to urban PM. - Repeated exposures to urban PM water extracts

  9. Control excess stock and calculating damaged products as the effort to increase revenue (case study of SME FBS)

    Science.gov (United States)

    Nurhasanah, N.; Mardhika, D. A.; Tanjung, W.; Gayatri, A. M.; Suri, Q. A.; Jingga; Safitri, R.; Supriyanto, A.

    2017-12-01

    Of small and medium scale (SME) is a business engaged in production. The growth product innovation of each year to year made competitiveness every SME very tight, and the sales must be high that avoid goods the product last year will be tough sold in the following year. Forecasting demand is needed so that no its production. In production process, besides products should also be considered about damaged products, resulting in a loss. In this study, researchers conducted a observations on SME FBS producing pants, shirts and shirts. SME FBS not having planning previous production, also in any period of production there always products be damaged. This study attempts to increase their SME FBS by controlling waste products, and those damaged products. According to the research conducted other products in some excess pants 1609 unit, and the shirts 187911 unit, and increase the income through control over the excess product obtained by 1% to the pants, and 52% to the shirts. For damaged product on period last year and future, increase 0.07% if the damaged on shirts can be sold, and 0.29% on pants if the broken sold.