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Sample records for alleviating oxidative damage

  1. Alleviating CTAC and Flu combined pollution damage in Chlorella vulgaris by exogenous nitric oxide.

    PubMed

    Li, Qi; Liang, Zhijie; Ge, Fei; Xu, Yin; Yang, Liang; Zeng, Hui

    2014-02-01

    This study investigates the effect of sodium nitroprussiate (SNP), an exogenous NO-donor, on the joint toxicity of binary mixtures of cetyltrimethylammonium chloride (CTAC) and fluoranthene (Flu) (CTAC/Flu), which are representatives for surfactants and polycyclic aromatic hydrocarbons (PAHs) respectively, in a unicellular green alga Chlorella vulgaris (C. vulgaris). The results showed that the addition of low SNP (20μM) alleviated the CTAC/Flu combined pollution damage in C. vulgaris. Supplement of low SNP significantly increased the algae biomass, chlorophyll content, soluble protein content and the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) as compared to CTAC/Flu treatment alone. SNP also reduced the content of malondialdehyde (MDA) and the reactive oxygen species (ROS), as compared with CTAC/Flu treated alone. On the contrary, the above phenomena were reversed when high concentration of SNP (100μM) was added. Our study indicated that the damage of the joint action of surfactants and PAHs on hydrobios can be alleviated through protecting against oxidant substances and increasing the activity of antioxidant enzymes with an exogenous supply of NO in certain concentration range.

  2. Nitric oxide alleviates oxidative damage induced by high temperature stress in wheat.

    PubMed

    Bavita, A; Shashi, B; Navtej, S B

    2012-05-01

    Effect of sodium nitroprusside (SNP), a donor of nitric oxide (NO) was examined in two wheat (Triticum aestivum L.) cultivars, C 306 (heat tolerant) and PBW 550 (comparatively heat susceptible) to study the extent of oxidative injury and activities of antioxidant enzyme in relation to high temperature (HT) stress. HT stress resulted in a marked decrease in membrane thermostability (MTS) and 2, 3, 5-triphenyl tetrazolium chloride (TTC) cell viability whereas content of lipid peroxide increased in both the cultivars. The tolerant cultivar C 306 registered less damage to cellular membranes compared to PBW 550 under HT stress. Activities of antioxidant enzymes viz, superoxide dismutase, catalase, ascorbate peroxidase, guaicol peroxidase and glutathione reductase increased with HT in both the cultivars. Following treatment with SNP, activities of all antioxidant enzymes further increased in correspondence with an increase in MTS and TTC. Apparently, lipid peroxide content was reduced by SNP more in shoots of heat tolerant cultivar C 306 indicating better protection over roots under HT stress. The up-regulation of the antioxidant system by NO possibly contributed to better tolerance against HT induced oxidative damage in wheat.

  3. Roles of hydrogen sulfide and nitric oxide in the alleviation of cadmium-induced oxidative damage in alfalfa seedling roots.

    PubMed

    Li, Le; Wang, Yanqin; Shen, Wenbiao

    2012-06-01

    Despite hydrogen sulfide (H(2)S) and nitric oxide (NO) are important endogenous signals or bioregulators involved in many vital aspects of plant growth and responses against abiotic stresses, little information was known about their interaction. In the present study, we evaluated the effects of H(2)S and NO on alfalfa (Medicago sativa L.) plants exposed to cadmium (Cd) stress. Pretreatment with an H(2)S donor sodium hydrosulfide (NaHS) and well-known NO donor sodium nitroprusside (SNP) decreased the Cd toxicity. This conclusion was supported by the decreases of lipid peroxidation as well as the amelioration of seedling growth inhibition and Cd accumulation, in comparison with the Cd-stressed alone plants. Total activities and corresponding transcripts of antioxidant enzymes, including superoxide dismutase, peroxidase and ascorbate peroxidase were modulated differentially, thus leading to the alleviation of oxidative damage. Effects of H(2)S above were reversed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO), the specific scavenger of NO. By using laser confocal scanning microscope combined with Greiss reagent method, further results showed that NO production increased significantly after the NaHS pretreatment regardless of whether Cd was applied or not, all of which were obviously inhibited by cPTIO. These decreases of NO production were consistent with the exaggerated syndromes associated with Cd toxicity. Together, above results suggested that NO was involved in the NaHS-induced alleviation of Cd toxicity in alfalfa seedlings, and also indicated that there exists a cross-talk between H(2)S and NO responsible for the increased abiotic stress tolerance.

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

    SciTech Connect

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

    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.

  5. Pioglitazone alleviates the mitochondrial apoptotic pathway and mito-oxidative damage in the d-galactose-induced mouse model.

    PubMed

    Prakash, Atish; Kumar, Anil

    2013-09-01

    Chronic injection of d-galactose can cause gradual deterioration in learning and memory capacity, and activates oxidative stress, mitochondrial dysfunction and apoptotic cell death in the brain of mice. Thus, it serves as an animal model of ageing. Recent evidence has shown that mild cognitive impairment in humans might be alleviated by treatment with piogliatzone (peroxisome proliferator-activated receptor gamma (PPARγ) agonists). To continue exploring the effects of piogliatzone in this model, we focused on behavioural alteration, oxidative damage, mitochondrial dysfunction and apoptosis in d-galactose-induced mice. The ageing model was established by administration of d-galactose (100 mg/kg) for 6 weeks. Pioglitazone (10 and 30 mg/kg) and bisphenol A diglycidyl ether (15 mg/kg) were given daily to d-galactose-induced senescent mice. The cognitive behaviour of mice was monitored using the Morris water maze. The anti-oxidant status and apoptotic activity in the ageing mice was measured by determining mito-oxidative parameters and caspase-3 activity in brain tissue. Systemic administration of d-galactose significantly increased behavioural alterations, biochemical parameters, mitochondrial enzymes, and activations of caspase-3 and acetylcholinesterase enzyme activity as compared with the control group. Piogliatzone treatment significantly improved behavioural abnormalities, biochemical, cellular alterations, and attenuated the caspase-3 and acetylcholinesterase enzyme activity as compared with the control. Furthermore, pretreatment of BADGE (PPARγ antagonist) with pioglitazone reversed the protective effect of pioglitazone in d-galactose-induced mice. The present study highlights the protective effects of pioglitzone against d-galactose-induced memory dysfunction, mito-oxidative damage and apoptosis through activation of PPARγ receptors. These findings suggest that pioglitazone might be helpful for the prevention or alleviation of ageing.

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

    PubMed

    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.

  7. Pomegranate from Oman Alleviates the Brain Oxidative Damage in Transgenic Mouse Model of Alzheimer's disease

    PubMed Central

    Subash, Selvaraju; Essa, Musthafa Mohamed; Al-Asmi, Abdullah; Al-Adawi, Samir; Vaishnav, Ragini; Braidy, Nady; Manivasagam, Thamilarasan; Guillemin, Gilles J.

    2014-01-01

    Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology. Pomegranates (石榴 Shí Liú) contain very high levels of antioxidant polyphenolic substances, as compared to other fruits and vegetables. Polyphenols have been shown to be neuroprotective in different model systems. Here, the effects of the antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status were tested in the AD transgenic mouse. The 4-month-old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA. Four-month-old Tg2576 mice were fed with 4% pomegranate or control diet for 15 months and then assessed for the influence of diet on oxidative stress. Significant increase in oxidative stress was found in terms of enhanced levels of lipid peroxidation (LPO) and protein carbonyls. Concomitantly, decrease in the activities of antioxidant enzymes was observed in Tg2576 mice treated with control diet. Supplementation with 4% pomegranate attenuated oxidative damage, as evidenced by decreased LPO and protein carbonyl levels and restoration in the activities of the antioxidant enzymes [superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione (GSH), and Glutathione S transferase (GST)]. The activities of membrane-bound enzymes [Na+ K+-ATPase and acetylcholinesterase (AChE)] were altered in the brain regions of Tg2576 mouse treated with control diet, and 4% pomegranate supplementation was able to restore the activities of enzymes to comparable values observed in controls. The results suggest that the therapeutic potential of 4% pomegranate in the treatment of AD might be associated with counteracting the oxidative stress by the presence of active phytochemicals in it. PMID:25379464

  8. Selenium Alleviates Oxidative Stress and Lung Damage Induced by Aluminum Chloride in Adult Rats: Biochemical and Histological Approach.

    PubMed

    Ghorbel, Imen; Elwej, Awatef; Chaabane, Mariem; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Zeghal, Najiba

    2017-03-01

    Our study pertains to the potential ability of selenium, used as a nutritional supplement, to alleviate oxidative stress induced by aluminum chloride in the lung tissue. Rats have received during 21 days either aluminum chloride (AlCl3) (400 ppm) via drinking water, AlCl3 associated with Na2SeO3 (0.5 mg/kg of diet), or only Na2SeO3. Exposure of rats to AlCl3 induced lung oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. An alteration of lactate dehydrogenase activities and antioxidant redox status, enzymatic (catalase, superoxide dismutase, and glutathione peroxidase), and non-enzymatic (non-protein thiols, glutathione, metallothionein, and vitamin C) was also observed. These biochemical modifications were substantiated by histopathological data showing alveolar edema, a large number of hemosiderin-laden macrophages, and emphysema. Se supplementation attenuated the levels of oxidative stress by restoring antioxidant state and improved lung histological damage. Our results revealed that Se, a trace element with antioxidant properties, was effective in preventing lung damage.

  9. Carvedilol alleviates testicular and spermatological damage induced by cisplatin in rats via modulation of oxidative stress and inflammation.

    PubMed

    Eid, Ahmed H; Abdelkader, Noha F; Abd El-Raouf, Ola M; Fawzy, Hala M; El-Denshary, Ezz-El-Din S

    2016-12-01

    The clinical application of the anticancer drug cisplatin is limited by its deleterious side effects, including male reproductive toxicity. In this context, the potential protective effect of carvedilol on testicular and spermatological damage induced by cisplatin in male Sprague-Dawley rats was investigated. Carvedilol was orally administered at a dose of 10 mg/kg for 2 weeks, and cisplatin was given as a single intraperitoneal injection of 10 mg/kg on the 12th day to induce toxicity. Cisplatin significantly reduced reproductive organ weight, sperm count and sperm motility, and increased sperm abnormalities and histopathological damage of testicular tissue. In addition, it resulted in a significant decline in serum testosterone as well as levels of testicular enzymatic and non-enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxides, and reduced glutathione). Moreover, cisplatin remarkably augmented malondialdehyde, nitric oxide, tumor necrosis factor-α, and nuclear factor-kappa B contents in testicular tissue. Conversely, carvedilol administration markedly mitigated cisplatin-induced testicular and spermatological injury as demonstrated by suppression of oxidative/nitrosative and inflammatory burden, amendment of antioxidant defenses, enhancement of steroidogenesis and spermatogenesis, and mitigation of testicular histopathological damage. The current study reveals a promising protective action of carvedilol against cisplatin-induced reproductive toxicity by virtue of its anti-inflammatory and antioxidant properties.

  10. Salicylic acid alleviates aluminum toxicity in rice seedlings better than magnesium and calcium by reducing aluminum uptake, suppressing oxidative damage and increasing antioxidative defense.

    PubMed

    Pandey, Poonam; Srivastava, Rajneesh Kumar; Dubey, R S

    2013-05-01

    Aluminum toxicity is a major constraint to crop production in acid soils. The present study was undertaken to examine the comparative ameliorating effects of salicylic acid, Ca and Mg on Al toxicity in rice (Oryza sativa L.) seedlings grown in hydroponics. Al treatment (0.5 mM AlCl3) caused decrease in plant vigour, loss of root plasma membrane integrity, increased contents of O 2 (∙-) , H2O2, lipid peroxidation, protein carbonyls and decline in the level of protein thiol. Al treatment caused significant changes in activity of antioxidative enzymes in rice seedlings. Exogenously added salicylic acid (60 μM), Ca (1 mM) and Mg (0.25 mM) significantly alleviated Al toxicity effects in the seedlings marked by restoration of growth, suppression of Al uptake, restoration of root plasma membrane integrity and decline in O 2 (∙-) , H2O2, lipid peroxidation and protein carbonyl contents. Salicylic acid, Ca and Mg suppressed Al-induced increase in SOD, GPX and APX activities while it elevated Al-induced decline in CAT activity. By histochemical staining of O 2 (∙-) using NBT and H2O2 using DAB, it was further confirmed that added salicylic acid, Ca or Mg decreased Al-induced accumulation of O 2 (∙-) and H2O2 in the leaf tissues. Results indicate that exogenously added salicylic acid, Ca or Mg alleviates Al toxicity in rice seedlings by suppressing Al uptake, restoring root membrane integrity, reducing ROS level and ROS induced oxidative damage and regulating the level of antioxidative enzyme activities. Further salicylic appears to be superior to Mg and Ca in alleviating Al toxicity effects in rice plants.

  11. Citric acid enhances the phytoextraction of chromium, plant growth, and photosynthesis by alleviating the oxidative damages in Brassica napus L.

    PubMed

    Afshan, Sehar; Ali, Shafaqat; Bharwana, Saima Aslam; Rizwan, Muhammad; Farid, Mujahid; Abbas, Farhat; Ibrahim, Muhammad; Mehmood, Muhammad Aamer; Abbasi, Ghulam Hasan

    2015-08-01

    Chromium (Cr) toxicity is widespread in crops grown on Cr-contaminated soils and has become a serious environmental issue which requires affordable strategies for the remediation of such soils. This study was performed to assess the performance of citric acid (CA) through growing Brassica napus in the phytoextraction of Cr from contaminated soil. Different Cr (0, 100, and 500 μM) and citric acid (0, 2.5, and 5.0 mM) treatments were applied alone and in combinations to 4-week-old seedlings of B. napus plants in soil under wire house condition. Plants were harvested after 12 weeks of sowing, and the data was recorded regarding growth characteristics, biomass, photosynthetic pigments, malondialdehyde (MDA), electrolytic leakage (EL), antioxidant enzymes, and Cr uptake and accumulation. The results showed that the plant growth, biomass, chlorophyll contents, and carotenoid as well as soluble protein concentrations significantly decreased under Cr stress alone while these adverse effects were alleviated by application of CA. Cr concentration in roots, stem, and leaves of CA-supplied plant was significantly reduced while total uptake of Cr increased in all plant parts with CA application. Furthermore, in comparison with Cr treatments alone, CA supply reduced the MDA and EL values in both shoots and roots. Moreover, the activity of superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in shoots and roots markedly increased by 100 μM Cr exposure, while decreased at 500 μM Cr stress. CA application enhanced the activities of antioxidant enzymes compared to the same Cr treatment alone. Thus, the data indicate that exogenous CA application can increase Cr uptake and can minimize Cr stress in plants and may be beneficial in accelerating the phytoextraction of Cr through hyper-accumulating plants such as B. napus.

  12. Nitrate reductase-mediated early nitric oxide burst alleviates oxidative damage induced by aluminum through enhancement of antioxidant defenses in roots of wheat (Triticum aestivum).

    PubMed

    Sun, Chengliang; Lu, Lingli; Liu, Lijuan; Liu, Wenjing; Yu, Yan; Liu, Xiaoxia; Hu, Yan; Jin, Chongwei; Lin, Xianyong

    2014-03-01

    • Nitric oxide (NO) is an important signaling molecule involved in the physiological processes of plants. The role of NO release in the tolerance strategies of roots of wheat (Triticum aestivum) under aluminum (Al) stress was investigated using two genotypes with different Al resistances. • An early NO burst at 3 h was observed in the root tips of the Al-tolerant genotype Jian-864, whereas the Al-sensitive genotype Yang-5 showed no NO accumulation at 3 h but an extremely high NO concentration after 12 h. Stimulating NO production at 3 h in the root tips of Yang-5 with the NO donor relieved Al-induced root inhibition and callose production, as well as oxidative damage and ROS accumulation, while elimination of the early NO burst by NO scavenger aggravated root inhibition in Jian-864. • Synthesis of early NO in roots of Jian-864 was mediated through nitrate reductase (NR) but not through NO synthase. Elevated antioxidant enzyme activities were induced by Al stress in both wheat genotypes and significantly enhanced by NO donor, but suppressed by NO scavenger or NR inhibitor. • These results suggest that an NR-mediated early NO burst plays an important role in Al resistance of wheat through modulating enhanced antioxidant defense to adapt to Al stress.

  13. Nesfatin-1 alleviates extrahepatic cholestatic damage of liver in rats

    PubMed Central

    Solmaz, Ali; Gülçiçek, Osman Bilgin; Erçetin, Candaş; Yiğitbaş, Hakan; Yavuz, Erkan; Arıcı, Sinan; Erzik, Can; Zengi, Oğuzhan; Demirtürk, Pelin; Çelik, Atilla; Çelebi, Fatih

    2016-01-01

    Obstructive jaundice (OJ) can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8), control (n = 8), and nesfatin (n = 8). After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114). Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032). Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75). DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects. PMID:27524109

  14. Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline.

    PubMed

    Kang, Yunxiao; Yan, Wensheng; Fang, Hui; Zhang, Guoliang; Du, Yakun; Wang, Lei; Cui, Huixian; Shi, Geming

    2017-01-01

    The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.

  15. Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

    PubMed Central

    Yan, Wensheng; Fang, Hui; Zhang, Guoliang; Du, Yakun; Wang, Lei; Cui, Huixian

    2017-01-01

    The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients. PMID:28386312

  16. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes.

    PubMed

    Daverey, Amita; Agrawal, Sandeep K

    2016-10-01

    Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerative diseases. In the present study, alleviation of oxidative stress through curcumin is investigated in A172 (human glioblastoma cell line) and HA-sp (human astrocytes cell line derived from the spinal cord) astrocytes. H2O2 was used to induce oxidative stress in astrocytes (A172 and HA-sp). Data show that H2O2 induces activation of astrocytes in dose- and time-dependent manner as evident by increased expression of GFAP in A172 and HA-sp cells after 24 and 12h respectively. An upregulation of Prdx6 was also observed in A172 and HA-sp cells after 24h of H2O2 treatment as compared to untreated control. Our data also showed that curcumin inhibits oxidative stress-induced cytoskeleton disarrangement, and impedes the activation of astrocytes by inhibiting upregulation of GFAP, vimentin and Prdx6. In addition, we observed an inhibition of oxidative stress-induced inflammation, apoptosis and mitochondria fragmentation after curcumin treatment. Therefore, our results suggest that curcumin not only protects astrocytes from H2O2-induced oxidative stress but also reverses the mitochondrial damage and dysfunction induced by oxidative stress. This study also provides evidence for protective role of curcumin on astrocytes by showing its effects on attenuating reactive astrogliosis and inhibiting apoptosis.

  17. The sub/supra-optimal temperature-induced inhibition of photosynthesis and oxidative damage in cucumber leaves are alleviated by grafting onto figleaf gourd/luffa rootstocks.

    PubMed

    Li, Hao; Wang, Feng; Chen, Xiao-Juan; Shi, K; Xia, Xiao-Jian; Considine, Michael J; Yu, Jing-Quan; Zhou, Yan-Hong

    2014-11-01

    Shoot-root communication is involved in plant stress responses, but its mechanism is largely unknown. To determine the role of roots in stress tolerance, cucumber (Cucumis sativus) shoots from plants with roots of their own or with figleaf gourd (Cucurbita ficifolia, a chilling-tolerant species) or luffa (Luffa cylindrica (L.) M. Roem., a heat-tolerant species) rootstocks were exposed to low (18/13°C), optimal (27/22°C) and high (36/31°C) temperatures, respectively. Grafting onto figleaf gourd and luffa rootstocks significantly alleviated chilling and heat-induced reductions, respectively, in biomass production and CO(2) assimilation capacity in the shoots, while levels of lipid peroxidation and protein oxidation were decreased. Figleaf gourd and luffa rootstocks upregulated a subset of stress-responsive genes involved in signal transduction (MAPK1 and RBOH), transcriptional regulation (MYB and MYC), protein protection (HSP45.9 and HSP70), the antioxidant response (Cu/Zn-SOD, cAPX and GR), and photosynthesis (RBCL, RBCS, RCA and FBPase) at low and high growth temperatures, respectively, and this was accompanied by increased activity of the encoded enzymes and reduced glutathione redox homeostasis in the leaves. Moreover, Heat Shock Protein 70 (HSP70) expression in cucumber leaves was strongly induced by the luffa rootstock at the high growth temperature but slightly induced by the figleaf gourd rootstock at low or high growth temperatures. These results indicate that rootstocks could induce significant changes in the transcripts of stress-responsive and defense-related genes, and the ROS scavenging activity via unknown signals, especially at stressful growth temperatures, and this is one of mechanisms involved in the grafting-induced stress tolerance.

  18. Selenium Polysaccharide SPMP-2a from Pleurotus geesteranus Alleviates H2O2-Induced Oxidative Damage in HaCaT Cells

    PubMed Central

    Zhou, Cheng; Huang, Shoucheng

    2017-01-01

    Selenium- (Se-) enriched polysaccharide SPMP-2a was extracted and purified from Pleurotus geesteranus. SPMP-2a is a white flocculent polysaccharide and soluble in water, with a molecular weight of 3.32 × 104 Da. Fourier transform infrared spectroscopy spectral analysis indicated that it belongs to an acid Se polysaccharide with α-D-glucopyranoside bond. The effects of Se polysaccharide SPMP-2a in P. geesteranus against hydrogen peroxide- (H2O2-) induced oxidative damage in human keratinocytes (HaCaT) cells were evaluated further. Reduced cell viability and elevated apoptotic rates in H2O2-treated HaCaT cells were proven by MTT and flow cytometry assays. Hoechst 33342 staining revealed chromatin condensations in the nuclei of HaCaT cells. However, with the addition of SPMP-2a, cell viability improved, nuclear condensation declined, and cell apoptotic rates dropped significantly. Ultrastructural observation consistently revealed that treatments with SPMP-2a reduced the number of swollen and vacuolar mitochondria in the H2O2-treated cells compared with the controls. Furthermore, SPMP-2a increased the superoxide dismutase (SOD) and catalase (CAT) activities and reduced reactive oxygen species (ROS) content. Western blot analysis showed that SPMP-2a treatment effectively increased B-cell lymphoma 2 (Bcl-2) protein expression. Therefore, SPMP-2a could improve cellular antioxidant enzyme activities, reduce ROS levels, and increase Bcl-2 protein expression levels, thereby reducing cell apoptosis and protecting HaCaT cells from H2O2-induced oxidative damage. PMID:28293636

  19. Oregano Essential Oil Induces SOD1 and GSH Expression through Nrf2 Activation and Alleviates Hydrogen Peroxide-Induced Oxidative Damage in IPEC-J2 Cells

    PubMed Central

    Zou, Yi; Wang, Jun; Peng, Jian

    2016-01-01

    Oregano essential oil (OEO) has long been used to improve the health of animals, particularly their intestinal health. The health benefits of OEO are generally attributed to antioxidative actions, but the mechanisms remain unclear. Here, we investigate the antioxidative effects of OEO and their underlying molecular mechanisms in porcine small intestinal epithelial (IPEC-J2) cells. We found that OEO treatment prior to hydrogen peroxide (H2O2) exposure increased cell viability and prevented lactate dehydrogenase (LDH) release into the medium. H2O2-induced reactive oxygen species (ROS) and malondialdehyde (MDA) were remarkably suppressed by OEO. OEO dose-dependently increased mRNA and protein levels of the nuclear factor-erythroid 2-related factor-2 (Nrf2) target genes Cu/Zn-superoxide dismutase (SOD1) and g-glutamylcysteine ligase (GCLC, GLCM), as well as intracellular concentrations of SOD1 and glutathione. OEO also increased intranuclear expression of Nrf2 and the activity of an antioxidant response element reporter plasmid in IPEC-J2 cells. The OEO-induced expression of Nrf2-regulated genes and increased SOD1 and glutathione concentrations in IPEC-J2 cells were reduced by Nrf2 small interfering (si) RNAs, counteracting the protective effects of OEO against oxidative stress in IPEC-J2 cells. Our results suggest that OEO protects against H2O2-induced IPEC-J2 cell damage by inducing Nrf2 and related antioxidant enzymes. PMID:28105249

  20. Oregano Essential Oil Induces SOD1 and GSH Expression through Nrf2 Activation and Alleviates Hydrogen Peroxide-Induced Oxidative Damage in IPEC-J2 Cells.

    PubMed

    Zou, Yi; Wang, Jun; Peng, Jian; Wei, Hongkui

    2016-01-01

    Oregano essential oil (OEO) has long been used to improve the health of animals, particularly their intestinal health. The health benefits of OEO are generally attributed to antioxidative actions, but the mechanisms remain unclear. Here, we investigate the antioxidative effects of OEO and their underlying molecular mechanisms in porcine small intestinal epithelial (IPEC-J2) cells. We found that OEO treatment prior to hydrogen peroxide (H2O2) exposure increased cell viability and prevented lactate dehydrogenase (LDH) release into the medium. H2O2-induced reactive oxygen species (ROS) and malondialdehyde (MDA) were remarkably suppressed by OEO. OEO dose-dependently increased mRNA and protein levels of the nuclear factor-erythroid 2-related factor-2 (Nrf2) target genes Cu/Zn-superoxide dismutase (SOD1) and g-glutamylcysteine ligase (GCLC, GLCM), as well as intracellular concentrations of SOD1 and glutathione. OEO also increased intranuclear expression of Nrf2 and the activity of an antioxidant response element reporter plasmid in IPEC-J2 cells. The OEO-induced expression of Nrf2-regulated genes and increased SOD1 and glutathione concentrations in IPEC-J2 cells were reduced by Nrf2 small interfering (si) RNAs, counteracting the protective effects of OEO against oxidative stress in IPEC-J2 cells. Our results suggest that OEO protects against H2O2-induced IPEC-J2 cell damage by inducing Nrf2 and related antioxidant enzymes.

  1. Avocado oil induces long-term alleviation of oxidative damage in kidney mitochondria from type 2 diabetic rats by improving glutathione status.

    PubMed

    Ortiz-Avila, Omar; Figueroa-García, María Del Consuelo; García-Berumen, Claudia Isabel; Calderón-Cortés, Elizabeth; Mejía-Barajas, Jorge A; Rodriguez-Orozco, Alain R; Mejía-Zepeda, Ricardo; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2017-04-01

    Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

  2. Damage in the dorsal striatum alleviates addictive behavior.

    PubMed

    Muskens, J B; Schellekens, A F A; de Leeuw, F E; Tendolkar, I; Hepark, S

    2012-01-01

    The ventral striatum has been assigned a major role in addictive behavior. In addition, clinical lesion studies have described involvement of the insula and globus pallidus. To the best of our knowledge, this is the first report of alleviation of alcohol and nicotine addiction after a cerebrovascular incident in the dorsal striatum. The patient was still abstinent from alcohol and nicotine at follow-up. This observation suggests that the dorsal striatum may play a critical role in addiction to alcohol and nicotine.

  3. Ascorbic Acid Alleviates Pancreatic Damage Induced by Dibutyltin Dichloride (DBTC) in Rats

    PubMed Central

    Song, Yan-Hua; Fu, Yan-Biao; Qian, Ke-Da

    2007-01-01

    Purpose Because previous studies have reported depleted antioxidant capacity in patients with chronic pancreatitis (CP), prevention of free radical production has gained importance in antifibrotic treatment strategies for CP. The aim of this study was to investigate the effects of ascorbic acid on oxidative capacity and pancreatic damage in experimental CP. Materials and Methods CP was induced in male Sprague-Dawley rats by infusion of dibutyltin dichloride (DBTC) into the tail vein. Ascorbic acid was given intraperitoneally at a daily dose of 10 mg/kg body weight. The treatment groups were as follows: group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline. Each group contained 15 animals. Treatment was started after CP was established. After 4 weeks of treatment, serum hyaluronic acid and laminin levels were determined by radioimmunoassay, pancreatic tissue oxidative stress was analyzed, and the degree of pancreatic damage was determined. Results Ascorbic acid treatment markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). Significant serum hyaluronic acid and laminin reductions were observed in group 2 as compared with group 1 (p < 0.05). However, the serum hyaluronic acid and laminin levels remained elevated when compared with those of groups 3 and 4 (p < 0.05). Histopathologic scores were also lower in animals with CP that underwent ascorbic acid-treatment (p < 0.05). Conclusion Ascorbic acid treatment alleviated the degree of oxidative stress and pancreatic damage in rat CP. Antioxidant treatment might be considered a potential option to improve the pathologic process in CP. PMID:18159597

  4. Modified halloysite nanotubes and the alleviation of kidney damage induced by dietary zearalenone in swine.

    PubMed

    Jia, Zhiqiang; Yin, Shutong; Liu, Min; Zhang, Yuanyuan; Gao, Rui; Shi, Baoming; Shan, Anshan; Chen, Zhihui

    2015-01-01

    The aims of this study were, first, to investigate the toxicity of zearalenone (ZEN) through the analysis of biochemical parameters, oxidative stress, pathological changes and inflammatory response in the kidney of gestation sows and offspring; and, second, to evaluate the efficacy of modified halloysite nanotubes (MHNTs) for the alleviation to the adverse effects induced by ZEN. This study focused on the period of organogenesis between days 35 and 70 of gestation, and treatments included (1) a control diet; (2) contaminated grain (50% control corn and 50% mouldy corn); and (3) contaminated grain (50% control corn and 50% mouldy corn) + 1% MHNTs. ZEN treatment significantly increased most of the biochemical parameters and inflammatory cytokines and degenerative changes in the kidney and induced oxidative damage in plasma, whereas the addition of MHNTs in combination with ZEN induced a re-establishment of the biochemical parameters, the plasma oxidative stress enzyme activities and the normal histology of the kidney. Thus, the data strongly suggest that the deleterious effects of ZEN can be significantly diminished by MHNTs.

  5. Dexamethasone alleviates tumor-associated brain damage and angiogenesis.

    PubMed

    Fan, Zheng; Sehm, Tina; Rauh, Manfred; Buchfelder, Michael; Eyupoglu, Ilker Y; Savaskan, Nicolai E

    2014-01-01

    Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA), a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc-; SLC7a11) and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G) resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage.

  6. Dexamethasone Alleviates Tumor-Associated Brain Damage and Angiogenesis

    PubMed Central

    Fan, Zheng; Sehm, Tina; Rauh, Manfred; Buchfelder, Michael

    2014-01-01

    Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA), a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc−; SLC7a11) and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G) resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage. PMID:24714627

  7. Role of magnesium in carbon partitioning and alleviating photooxidative damage.

    PubMed

    Cakmak, Ismail; Kirkby, Ernest A

    2008-08-01

    effectively delayed by partial shading of the leaf blade, although the Mg concentrations in different parts of the leaf blade were unaffected by shading. The results indicate that photooxidative damage contributes to development of leaf chlorosis under Mg deficiency, suggesting that plants under high-light conditions have a higher physiological requirement for Mg. Maintenance of a high Mg nutritional status of plants is, thus, essential in the avoidance of ROS generation, which occurs at the expense of inhibited phloem export of sugars and impairment of CO2 fixation, particularly under high-light conditions.

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

    PubMed

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

    2016-11-01

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

  9. Oxidative damage in dengue fever.

    PubMed

    Seet, Raymond C S; Lee, Chung-Yung J; Lim, Erle C H; Quek, Amy M L; Yeo, Leonard L L; Huang, Shan-Hong; Halliwell, Barry

    2009-08-15

    Oxidative stress may be important in the pathogenesis of dengue infection. Using accurate markers of oxidative damage, we assessed the extent of oxidative damage in dengue patients. The levels of hydroxyeicosatetraenoic acid products (HETEs), F(2)-isoprostanes (F(2)-IsoPs), and cholesterol oxidation products (COPs) were measured in 28 adult dengue patients and 28 age-matched study controls during the febrile, defervescent, and convalescent stages of infection. We compared the absolute and the percentage change in these markers in relation to key clinical parameters and inflammatory markers. The levels of total HETEs and total HETEs/arachidonate, total F(2)-IsoPs/arachidonate, and COPs/cholesterol were higher during the febrile compared to the convalescent level. Total HETEs correlated positively with admission systolic blood pressure (r=0.52, p<0.05), whereas an inverse relationship was found between 7beta-hydroxycholesterol and systolic and diastolic blood pressure (r=-0.61 and -0.59, respectively, p<0.01). The urinary F(2)-IsoP level was higher in urine during the febrile stage compared to the convalescent level. Despite lower total cholesterol levels during the febrile stage compared to convalescent levels, a higher percentage of cholesterol was found as COPs (7beta-, 24-, and 27-hydroxycholesterol). The levels of platelet-activating factor-acetylhydrolase activity, vascular cellular adhesion molecule-1, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein were higher during the febrile stage compared to their convalescent levels (p<0.01). Markers of oxidative damage are altered during the various stages of dengue infection.

  10. Nitric oxide (NO) in alleviation of heavy metal induced phytotoxicity and its role in protein nitration.

    PubMed

    Saxena, Ina; Shekhawat, G S

    2013-08-01

    Nitric oxide (NO) is recognized as a biological messenger in various tissues to regulate diverse range of physiological process including growth, development and response to abiotic and biotic factors. The NO emission from plants is known since the 1970s, and there is copious information on the multiple effects of exogenously applied NO on different physiological and biochemical processes of plants. Heavy metal toxicity is one of the major abiotic stresses leading to hazardous effects in plants and its toxicity is based on chemical and physical property. A common consequence of heavy metal toxicity is the uncontrolled and excessive accumulation of reactive oxygen species (ROS) which leads to peroxidation of lipids, oxidation of protein, inactivation of enzymes, DNA damage and/or interact with other vital constituents of plant cells. Recently, an increasing number of articles have reported the effects of exogenous NO on alleviating heavy metal toxicity in plants but knowledge of physiological mechanisms of NO in alleviating heavy metal toxicity is quite limited, and some results contradict one another. Therefore, to help clarify the roles of NO in heavy metal tolerance, it is important to review and discuss the recent advances on this area of research. NO can provoke both beneficial and harmful effects, which depend on the concentration and location of NO in the plant cells. NO alleviates the harmfulness of the ROS, and reacts with other target molecules, and regulates the expression of stress responsive genes under various stress conditions. This manuscript includes, the latest advances in understanding the effects of endogenous NO on heavy metal toxicity and the mechanisms and role of NO as an antioxidant as well as in protein nitration are highlighted.

  11. Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation.

    PubMed

    Ahmad, Shiekh Tanveer; Arjumand, Wani; Nafees, Sana; Seth, Amlesh; Ali, Nemat; Rashid, Summya; Sultana, Sarwat

    2012-01-25

    Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The present study demonstrates the comparative hepatoprotective and nephroprotective activity of hesperidin (HD), a naturally occurring bioflavonoid against APAP induced toxicity. APAP induces hepatotoxicity and nephrotoxicity as was evident by abnormal deviation in the levels of antioxidant enzymes. Moreover, APAP induced renal damage by inducing apoptotic death and inflammation in renal tubular cells, manifested by an increase in the expression of caspase-3, caspase-9, NFkB, iNOS, Kim-1 and decrease in Bcl-2 expression. These results were further supported by the histopathological examination of kidney. All these features of APAP toxicity were reversed by the co-administration of HD. Therefore, our study favors the view that HD may be a useful modulator in alleviating APAP induced oxidative stress and toxicity.

  12. Querectin Alleviates Zinc Oxide Nanoreprotoxicity in Male Albino Rats.

    PubMed

    Hussein, Mohamed M A; Ali, Haytham A; Saadeldin, Islam M; Ahmed, Mona M

    2016-10-01

    Zinc oxide nanopartciles (ZnONPs) involved in advanced technologies, and their wide-scale use in consumer market makes human beings more prone to the exposure to ZnONPs. The present study was undertaken to evaluate amelioration of ZnONP-induced toxicities with querectin in male albino rats. ZnONPs-treated rats showed a significant decrease in sperm cell count, sperm motility, live and normal sperms, as well as serum testosterone level. Severe histopathological damage with a significant increase in lipid peroxidation and a decrease in antioxidant enzymes activity and the GSH level were observed in the affected testis. Relative quantitative polymerase chain reaction results showed a significant decrease in antioxidant enzymes (superoxide dismutase and catalase) and a significant decrease in 3β-HSD, 17β-HSD, and Nr5A1 transcripts. Rats-administered querectin along with ZnONPs showed less toxic effects on all studied reproductive traits and mRNA transcripts. Our results suggest that querectin is beneficial for preventing or ameliorating ZnONP reproductive toxicities in males.

  13. Strawberry consumption alleviates doxorubicin-induced toxicity by suppressing oxidative stress.

    PubMed

    Giampieri, Francesca; Alvarez-Suarez, Jose M; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Afrin, Sadia; Bompadre, Stefano; Rubini, Corrado; Zizzi, Antonio; Astolfi, Paola; Santos-Buelga, Celestino; González-Paramás, Ana M; Quiles, Josè L; Mezzetti, Bruno; Battino, Maurizio

    2016-08-01

    Doxorubicin (Dox), one of the most used chemotherapeutic agents, is known to generate oxidative stress and block DNA synthesis, which result in severe dose-limiting toxicity. A strategy to protect against Dox toxic effects could be to use dietary antioxidants of which fruits and vegetable are a rich source. In this context, strawberry consumption is associated with the maintenance of good health and the prevention of several diseases, thanks to the antioxidant capacities of its bioactive compounds. The aim of the present study was to evaluate the protective effects of strawberry consumption against oxidative stress induced by Dox in rats. Animals were fed with strawberry enriched diet (15% of the total calories) for two months and Dox (10 mg/kg; i.p.) was injected at the end of the experimental period. Strawberry consumption significantly inhibited ROS production and oxidative damage biomarkers accumulation in plasma and liver tissue and alleviated histopathological changes in rat livers treated with Dox. The reduction of antioxidant enzyme activities was significantly mitigated after strawberry consumption. In addition, strawberry enriched diet ameliorated liver mitochondrial antioxidant levels and functionality. In conclusion, strawberry intake protects against Dox-induced toxicity, at plasma, liver and mitochondrial levels thanks to its high contents of bioactive compounds.

  14. Lung oxidative damage by hypoxia.

    PubMed

    Araneda, O F; Tuesta, M

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described.

  15. Lung Oxidative Damage by Hypoxia

    PubMed Central

    Araneda, O. F.; Tuesta, M.

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

  16. Selenium alleviates cadmium toxicity by preventing oxidative stress in sunflower (Helianthus annuus) seedlings.

    PubMed

    Saidi, Issam; Chtourou, Yacine; Djebali, Wahbi

    2014-03-01

    The present study investigated the possible mediatory role of selenium (Se) in protecting plants from cadmium (Cd) toxicity. The exposure of sunflower seedlings to 20μM Cd inhibited biomass production, decreased chlorophyll and carotenoid concentrations and strongly increased accumulation of Cd in both roots and shoots. Similarly, Cd enhanced hydrogen peroxides content and lipid peroxidation as indicated by malondialdehyde accumulation. Pre-soaking seeds with Se (5, 10 and 20μM) alleviated the negative effect of Cd on growth and led to a decrease in oxidative injuries caused by Cd. Furthermore, Se enhanced the activities of catalase, ascorbate peroxidase and glutathione reductase, but lowered that of superoxide dismutase and guaiacol peroxidase. As important antioxidants, ascorbate and glutathione contents in sunflower leaves exposed to Cd were significantly decreased by Se treatment. The data suggest that the beneficial effect of Se during an earlier growth period could be related to avoidance of cumulative damage upon exposure to Cd, thus reducing the negative consequences of oxidative stress caused by heavy metal toxicity.

  17. Proteus mirabilis alleviates zinc toxicity by preventing oxidative stress in maize (Zea mays) plants.

    PubMed

    Islam, Faisal; Yasmeen, Tahira; Riaz, Muhammad; Arif, Muhammad Saleem; Ali, Shafaqat; Raza, Syed Hammad

    2014-12-01

    Plant-associated bacteria can have beneficial effects on the growth and health of their host. However, the role of plant growth promoting bacteria (PGPR), under metal stress, has not been widely investigated. The present study investigated the possible mandatory role of plant growth promoting rhizobacteria in protecting plants from zinc (Zn) toxicity. The exposure of maize plants to 50µM zinc inhibited biomass production, decreased chlorophyll, total soluble protein and strongly increased accumulation of Zn in both root and shoot. Similarly, Zn enhanced hydrogen peroxide, electrolyte leakage and lipid peroxidation as indicated by malondaldehyde accumulation. Pre-soaking with novel Zn tolerant bacterial strain Proteus mirabilis (ZK1) isolated zinc (Zn) contaminated soil, alleviated the negative effect of Zn on growth and led to a decrease in oxidative injuries caused by Zn. Furthermore, strain ZK1 significantly enhanced the activities of catalase, guaiacol peroxidase, superoxide dismutase and ascorbic acid but lowered the Proline accumulation in Zn stressed plants. The results suggested that the inoculation of Zea mays plants with P. mirabilis during an earlier growth period could be related to its plant growth promoting activities and avoidance of cumulative damage upon exposure to Zn, thus reducing the negative consequences of oxidative stress caused by heavy metal toxicity.

  18. Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide

    PubMed Central

    Paul, Manoj; Hemshekhar, Mahadevappa; Thushara, Ram M.; Sundaram, Mahalingam S.; NaveenKumar, Somanathapura K.; Naveen, Shivanna; Devaraja, Sannaningaiah; Somyajit, Kumar; West, Robert; Basappa; Nayaka, Siddaiah C.; Zakai, Uzma I.; Nagaraju, Ganesh; Rangappa, Kanchugarakoppal S.; Kemparaju, Kempaiah; Girish, Kesturu S.

    2015-01-01

    Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 μM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to ΔΨm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions. PMID:26083398

  19. Tissue damage and oxidant/antioxidant balance.

    PubMed

    Kisaoglu, Abdullah; Borekci, Bunyamin; Yapca, O Erkan; Bilen, Habib; Suleyman, Halis

    2013-02-01

    The oxidant/antioxidant balance in healthy tissues is maintained with a predominance of antioxidants. Various factors that can lead to tissue damage disrupt the oxidant/antioxidant balance in favor of oxidants. In this study, disruptions of the oxidant/antioxidant balance in favor of oxidants were found to be a consequence of the over-consumption of antioxidants. For this reason, antioxidants are considered to be of importance in the prevention and treatment of various types of tissue damage that are aggravated by stress.

  20. Arbuscular mycorrhizal fungi alleviate oxidative stress induced by ADOR and enhance antioxidant responses of tomato plants.

    PubMed

    García-Sánchez, Mercedes; Palma, José Manuel; Ocampo, Juan Antonio; García-Romera, Inmaculada; Aranda, Elisabet

    2014-03-15

    The behaviour of tomato plants inoculated with arbuscular mycorrhizal (AM) fungi grown in the presence of aqueous extracts from dry olive residue (ADOR) was studied in order to understand how this symbiotic relationship helps plants to cope with oxidative stress caused by ADOR. The influence of AM symbiosis on plant growth and other physiological parameters was also studied. Tomato plants were inoculated with the AM fungus Funneliformis mosseae and were grown in the presence of ADOR bioremediated and non-bioremediated by Coriolopsis floccosa and Penicillium chrysogenum-10. The antioxidant response as well as parameters of oxidative damage were examined in roots and leaves. The data showed a significant increase in the biomass of AM plant growth in the presence of ADOR, regardless of whether it was bioremediated. The establishment and development of the symbiosis were negatively affected after plants were exposed to ADOR. No differences were observed in the relative water content (RWC) or PS II efficiency between non-AM and AM plants. The increase in the enzymatic activities of superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6) and glutathione-S-transferase (GST; EC 2.5.1.18) were simultaneous to the reduction of MDA levels and H2O2 content in AM root growth in the presence of ADOR. Similar H2O2 levels were observed among non-AM and AM plants, although only AM plants showed reduced lipid peroxidation content, probably due to the involvement of antioxidant enzymes. The results highlight how the application of both bioremediated ADOR and AM fungi can alleviate the oxidative stress conditions, improving the growth and development of tomato plants.

  1. Tumour necrosis factor-α inhibition with lenalidomide alleviates tissue oxidative injury and apoptosis in ob/ob obese mice.

    PubMed

    Zhu, Xiaoling; Jiang, Shasha; Hu, Nan; Luo, Fuling; Dong, Hailong; Kang, Yu-Ming; Jones, Kyla R; Zou, Yunzeng; Xiong, Lize; Ren, Jun

    2014-07-01

    Lenalidomide (Revlimid; Selleck Chemicals, Houston, TX, USA), an analogue of thalidomide, possesses potent cytokine modulatory capacity through inhibition of cytokines such as tumour necrosis factor (TNF)-α, a cytokine pivotal for the onset and development of complications in obesity and diabetes mellitus. The present study was designed to evaluate the effect of lenalidomide on oxidative stress, protein and DNA damage in multiple organs in an ob/ob murine model of obesity. To this end, C57BL/6 lean and ob/ob obese mice were administered lenalidomide (50 mg/kg per day, p.o.) for 5 days. Oxidative stress, protein and DNA damage were assessed using the conversion of reduced glutathione (GSH) to oxidized glutathione (GSSG), carbonyl formation and Comet assay, respectively. Apoptosis was evaluated using caspase 3 activity, and levels of Bax, Bcl-2, Bip, caspase 8, caspase 9 and TNF-α were assessed using western blot analysis. Lenalidomide treatment did not affect glucose clearance in lean or ob/ob mice. Obese mice exhibited a reduced GSH/GSSG ratio in the liver, gastrocnemius skeletal muscle and small intestine, as well as enhanced protein carbonyl formation, DNA damage and caspase 3 activity in the liver, kidney, skeletal muscle and intestine; these effects were alleviated by lenalidomide, with the exception of obesity-associated DNA damage in the liver and kidney. Western blot analysis revealed elevated TNF-α, Bax, Bcl-2, Bip, caspase 8 and caspase 9 in ob/ob mice with various degrees of reversal by lenalidomide treatment. Together, these data indicate that lenalidomide protects against obesity-induced tissue injury and protein damage, possibly in association with antagonism of cytokine production and cytokine-induced apoptosis and oxidative stress.

  2. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

    PubMed

    Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

    2017-03-15

    It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress.

  3. Oxidative stress and oxidative damage in chemical carcinogenesis

    SciTech Connect

    Klaunig, James E. Wang Zemin; Pu Xinzhu; Zhou Shaoyu

    2011-07-15

    Reactive oxygen species (ROS) are induced through a variety of endogenous and exogenous sources. Overwhelming of antioxidant and DNA repair mechanisms in the cell by ROS may result in oxidative stress and oxidative damage to the cell. This resulting oxidative stress can damage critical cellular macromolecules and/or modulate gene expression pathways. Cancer induction by chemical and physical agents involves a multi-step process. This process includes multiple molecular and cellular events to transform a normal cell to a malignant neoplastic cell. Oxidative damage resulting from ROS generation can participate in all stages of the cancer process. An association of ROS generation and human cancer induction has been shown. It appears that oxidative stress may both cause as well as modify the cancer process. Recently association between polymorphisms in oxidative DNA repair genes and antioxidant genes (single nucleotide polymorphisms) and human cancer susceptibility has been shown.

  4. Aminoguanidine Alleviates Radiation-Induced Small-Bowel Damage Through Its Antioxidant Effect

    SciTech Connect

    Huang, E.-Y.; Wang, F.-S.; Lin, I-H.; Yang, Kuender D.

    2009-05-01

    Purpose: To evaluate the effect and its mechanism of aminoguanidine (AG) on small-bowel protection after whole-abdominal irradiation (WAI) in rats. Methods and Materials: Male Sprague-Dawley rats (300-400 g) subjected to 12 Gy WAI were used for the study. Aminoguanidine at a dose of 50-800 mg/kg was administered by the gavage route 2 h before WAI. Mucosal damage of small bowel was evaluated by the grade of diarrhea and crypt survival; oxidative stress was determined by the level of 8-hydroxy 2'-deoxyguanosine (8-OHdG) with immunohistochemistry (IHC). Nitrosative stress was evaluated by the expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) with IHC, and systemic and portal vein NOx (nitrite + nitrate) levels were measured and compared with and without AG treatment after WAI. Results: Aminoguanidine showed a dose-dependent effect against WAI-induced diarrhea. Aminoguanidine at a dose of 400 mg/kg had the best protective effect, from 92% to 17% (p = 0.002). Aminoguanidine increased crypt survival from 23% to 46% (p = 0.003). It also significantly attenuated 8-OHdG expression but not 3-NT and iNOS expression at both 4 and 8 h after 12-Gy WAI. Aminoguanidine did not alter the portal vein NOx levels 4 and 8 h after 12-Gy WAI. Conclusion: Aminoguanidine has a radioprotective effect against radiation-induced small-bowel damage due to its antioxidant effect but not inhibition of nitric oxide production. Dietary AG may have a potentially protective effect on the small intestine of patients subjected to pelvic and abdominal radiotherapies.

  5. Vitamin D3 pretreatment alleviates renal oxidative stress in lipopolysaccharide-induced acute kidney injury.

    PubMed

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Xia, Mi-Zhen; Wang, Hua; Zhao, Hui; Xu, De-Xiang; Yu, De-Xin

    2015-08-01

    Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3+LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renal p47phox and gp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renal superoxide dismutase (sod) 1 and sod2, two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes.

  6. The oxidative damage initiation hypothesis for meiosis.

    PubMed

    Hörandl, Elvira; Hadacek, Franz

    2013-12-01

    The maintenance of sexual reproduction in eukaryotes is still a major enigma in evolutionary biology. Meiosis represents the only common feature of sex in all eukaryotic kingdoms, and thus, we regard it a key issue for discussing its function. Almost all asexuality modes maintain meiosis either in a modified form or as an alternative pathway, and facultatively apomictic plants increase frequencies of sexuality relative to apomixis after abiotic stress. On the physiological level, abiotic stress causes oxidative stress. We hypothesize that repair of oxidative damage on nuclear DNA could be a major driving force in the evolution of meiosis. We present a hypothetical model for the possible redox chemistry that underlies the binding of the meiosis-specific protein Spo11 to DNA. During prophase of meiosis I, oxidized sites at the DNA molecule are being targeted by the catalytic tyrosine moieties of Spo11 protein, which acts like an antioxidant reducing the oxidized target. The oxidized tyrosine residues, tyrosyl radicals, attack the phosphodiester bonds of the DNA backbone causing DNA double strand breaks that can be repaired by various mechanisms. Polyploidy in apomictic plants could mitigate oxidative DNA damage and decrease Spo11 activation. Our hypothesis may contribute to explaining various enigmatic phenomena: first, DSB formation outnumbers crossovers and, thus, effective recombination events by far because the target of meiosis may be the removal of oxidative lesions; second, it offers an argument for why expression of sexuality is responsive to stress in many eukaryotes; and third, repair of oxidative DNA damage turns meiosis into an essential characteristic of eukaryotic reproduction.

  7. DNA damage, oxidative mutagen sensitivity, and repair of oxidative DNA damage in nonmelanoma skin cancer patients.

    PubMed

    Bendesky, Andrés; Michel, Alejandra; Sordo, Monserrat; Calderón-Aranda, Emma S; Acosta-Saavedra, Leonor C; Salazar, Ana M; Podoswa, Nancy; Ostrosky-Wegman, Patricia

    2006-08-01

    Nonmelanoma skin cancer (NMSC) is the most frequent type of cancer in humans. Exposure to UV radiation is a major risk factor for NMSC, and oxidative DNA damage, caused either by UV radiation itself or by other agents, may be involved in its induction. Increased sensitivity to oxidative damage and an altered DNA repair capacity (DRC) increase the risk of many types of cancer; however, sensitivity to oxidizing agents has not been evaluated for NMSC, and results regarding DRC in NMSC are inconclusive. In the present study, we evaluated DNA damage and repair in leukocytes from 41 NMSC patients and 45 controls. The Comet assay was used to measure basal and H(2)O(2)-induced DNA damage, as well as the DRC, while the cytokinesis-block micronucleus assay was used to measure the basal level of chromosome damage. Although basal DNA damage was higher for the controls than for the patients, this finding was mainly due to sampling more controls in the summer, which was associated with longer comet tails. In contrast, H(2)O(2)-induced DNA damage was significantly higher in cases than in controls, and this parameter was not influenced by the season of the year. The DRC for the H(2)O(2)-induced damage was similar for cases and controls and unrelated to seasonality. Finally, the frequency of binucleated lymphocytes with micronuclei was similar for cases and controls. The results of this study indicate that NMSC patients are distinguished from controls by an increased sensitivity to oxidative DNA damage.

  8. Antioxidant potential of Cymbopogon citratus extract: alleviation of carbon tetrachloride-induced hepatic oxidative stress and toxicity.

    PubMed

    Koh, Pei Hoon; Mokhtar, Ruzaidi Azli Mohd; Iqbal, Mohammad

    2012-01-01

    This study was aimed to evaluate the effect of Cymbopogon citratus against carbon tetrachloride (CCl(4))-mediated hepatic oxidative damage in rats. Rats were administrated with C. citratus extract (100, 200 and 300 mg/kg b.w.) for 14 days before the challenge of CCl(4) (1.2 ml/kg b.w. p.o) on 13th and 14th days. Hepatic damage was evaluated by employing serum biochemical parameters (alanine aminotransferase-ALT, aspartate aminotransferase-AST and lactate dehydrogenase-LDH), malondialdehye (MDA) level, reduced GSH and antioxidant enzymes (catalase: CAT, glutathione peroxidase: GPX, quinone reductase: QR, glutathione S-transferase: GST, glutathione reductase: GR, glucose-6-phosphate dehyrogenase: G6PD). In addition, CCl(4)-mediated hepatic damage was further evaluated by histopathological examination. However, most of these changes were alleviated by prophylactic treatment of animals with C. citratus dose dependently (p < 0.05). The protection was further evident through decreased histopathological alterations in liver. The results of the present study indicated that the hepatoprotective effect of C. citratus might be ascribable to its antioxidant and free radical scavenging property.

  9. Citric acid enhances the phytoextraction of manganese and plant growth by alleviating the ultrastructural damages in Juncus effusus L.

    PubMed

    Najeeb, U; Xu, L; Ali, Shafaqat; Jilani, Ghulam; Gong, H J; Shen, W Q; Zhou, W J

    2009-10-30

    Chelate-assisted phytoextraction by high biomass producing plant species enhances the removal of heavy metals from polluted environments. In this regard, Juncus effusus a wetland plant has great potential. This study evaluated the effects of elevated levels of manganese (Mn) on the vegetative growth, Mn uptake and antioxidant enzymes in J. effusus. We also studied the role of citric acid and EDTA on improving metal accumulation, plant growth and Mn toxicity stress alleviation. Three-week-old plantlets of J. effusus were subjected to various treatments in the hydroponics as: Mn (50, 100 and 500 microM) alone, Mn (500 microM) + citric acid (5 mM), and Mn (500 microM) + EDTA (5 mM). After 2 weeks of treatment, higher Mn concentrations significantly reduced the plant biomass and height. Both citric acid and EDTA restored the plant height as it was reduced at the highest Mn level. Only the citric acid (but not EDTA) was able to recover the plant biomass weight, which was also obvious from the microscopic visualization of mesophyll cells. There was a concentration dependent increase in Mn uptake in J. effusus plants, and relatively more deposition in roots compared to aerial parts. Although both EDTA and citric acid caused significant increase in Mn accumulation; however, the Mn translocation was enhanced markedly by EDTA. Elevated levels of Mn augmented the oxidative stress, which was evident from changes in the activities of antioxidative enzymes in plant shoots. Raised levels of lipid peroxidation and variable changes in the activities of antioxidant enzymes were recorded under Mn stress. Electron microscopic images revealed several modifications in the plants at cellular and sub-cellular level due to the oxidative damage induced by Mn. Changes in cell shape and size, chloroplast swelling, increased number of plastoglobuli and disruption of thylakoid were noticed. However, these plants showed a high degree of tolerance against Mn toxicity stress, and it removed

  10. Understanding and preventing mitochondrial oxidative damage

    PubMed Central

    Murphy, Michael P.

    2016-01-01

    Mitochondrial oxidative damage has long been known to contribute to damage in conditions such as ischaemia–reperfusion (IR) injury in heart attack. Over the past years, we have developed a series of mitochondria-targeted compounds designed to ameliorate or determine how this damage occurs. I will outline some of this work, from MitoQ to the mitochondria-targeted S-nitrosating agent, called MitoSNO, that we showed was effective in preventing reactive oxygen species (ROS) formation in IR injury with therapeutic implications. In addition, the protection by this compound suggested that ROS production in IR injury was mainly coming from complex I. This led us to investigate the mechanism of the ROS production and using a metabolomic approach, we found that the ROS production in IR injury came from the accumulation of succinate during ischaemia that then drove mitochondrial ROS production by reverse electron transport at complex I during reperfusion. This surprising mechanism led us to develop further new therapeutic approaches to have an impact on the damage that mitochondrial ROS do in pathology and also to explore how mitochondrial ROS can act as redox signals. I will discuss how these approaches have led to a better understanding of mitochondrial oxidative damage in pathology and also to the development of new therapeutic strategies. PMID:27911703

  11. Selenium alleviates chromium toxicity by preventing oxidative stress in cabbage (Brassica campestris L. ssp. Pekinensis) leaves.

    PubMed

    Qing, Xuejiao; Zhao, Xiaohu; Hu, Chengxiao; Wang, Peng; Zhang, Ying; Zhang, Xuan; Wang, Pengcheng; Shi, Hanzhi; Jia, Fen; Qu, Chanjuan

    2015-04-01

    The beneficial role of selenium (Se) in alleviation of chromium (Cr)-induced oxidative stress is well established. However, little is known about the underlying mechanism. The impacts of exogenous Se (0.1mg/L) on Cr(1mg/L)-induced oxidative stress and antioxidant systems in leaves of cabbage (Brassica campestris L. ssp. Pekinensis) were investigated by using cellular and biochemical approaches. The results showed that supplementation of the medium with Se was effective in reducing Cr-induced increased levels of lipid peroxides and superoxide free radicals (O(-)2(·)), as well as increasing activities of superoxide dismutase (SOD) and peroxidase (POD). Meanwhile, 1mg/L Cr induced loss of plasma membrane integrity, growth inhibition, as well as ultrastructural changes of leaves were significantly reversed due to Se supplementation in the medium. In addition, Se application significantly altered the subcellular distribution of Cr which transported from mitochondria, nucleus and the cell-wall material to the soluble fraction and chloroplasts. However, Se application did no significant alteration of Cr effects on osmotic adjustment accumulating products. The study suggested that Se is able to protect leaves of cabbage against Cr toxicity by alleviation of Cr induced oxidative stress, and re-distribution of Cr in the subcellular of the leaf. Furthermore, free radicals, lipid peroxides, activity of SOD and POD, and subcellular distribution of Cr can be considered the efficient biomarkers to indicate the efficiency of Se to detoxification Cr.

  12. Coccidian Infection Causes Oxidative Damage in Greenfinches

    PubMed Central

    Sepp, Tuul; Karu, Ulvi; Blount, Jonathan D.; Sild, Elin; Männiste, Marju; Hõrak, Peeter

    2012-01-01

    The main tenet of immunoecology is that individual variation in immune responsiveness is caused by the costs of immune responses to the hosts. Oxidative damage resulting from the excessive production of reactive oxygen species during immune response is hypothesized to form one of such costs. We tested this hypothesis in experimental coccidian infection model in greenfinches Carduelis chloris. Administration of isosporan coccidians to experimental birds did not affect indices of antioxidant protection (TAC and OXY), plasma triglyceride and carotenoid levels or body mass, indicating that pathological consequences of infection were generally mild. Infected birds had on average 8% higher levels of plasma malondialdehyde (MDA, a toxic end-product of lipid peroxidation) than un-infected birds. The birds that had highest MDA levels subsequent to experimental infection experienced the highest decrease in infection intensity. This observation is consistent with the idea that oxidative stress is a causative agent in the control of coccidiosis and supports the concept of oxidative costs of immune responses and parasite resistance. The finding that oxidative damage accompanies even the mild infection with a common parasite highlights the relevance of oxidative stress biology for the immunoecological research. PMID:22615772

  13. Targeted mRNA oxidation regulates sunflower seed dormancy alleviation during dry after-ripening.

    PubMed

    Bazin, Jérémie; Langlade, Nicolas; Vincourt, Patrick; Arribat, Sandrine; Balzergue, Sandrine; El-Maarouf-Bouteau, Hayat; Bailly, Christophe

    2011-06-01

    After-ripening is the mechanism by which dormant seeds become nondormant during their dry storage after harvest. The absence of free water in mature seeds does not allow detectable metabolism; thus, the processes associated with dormancy release under these conditions are largely unknown. We show here that sunflower (Helianthus annuus) seed alleviation of dormancy during after-ripening is associated with mRNA oxidation and that this oxidation is prevented when seeds are maintained dormant. In vitro approaches demonstrate that mRNA oxidation results in artifacts in cDNA-amplified fragment length polymorphim analysis and alters protein translation. The oxidation of transcripts is not random but selective, and, using microarrays, we identified 24 stored mRNAs that became highly oxidized during after-ripening. Oxidized transcripts mainly correspond to genes involved in responses to stress and in cell signaling. Among them, protein phosphatase 2C PPH1, mitogen-activated protein kinase phosphatase 1, and phenyl ammonia lyase 1 were identified. We propose that targeted mRNA oxidation during dry after-ripening of dormant seeds could be a process that governs cell signaling toward germination in the early steps of seed imbibition.

  14. Oxidative Damage in Parkinson’s Disease

    DTIC Science & Technology

    2001-10-01

    of Parkinson’s Disease and the MPTP model of Parkinsonism. In the past year, we have developed a novel column switching assay for measurement of...oxidative damage to DNA in human body fluids. We have applied to this plasma samples of Parkinson’s Disease patients. We have also developed a novel...methodology. We have found a relatively high mutation rate and control samples and intend to apply this to Parkinson’s Disease . We have continued our

  15. Inflammation, oxidative DNA damage, and carcinogenesis

    SciTech Connect

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

    1987-12-01

    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/sub 2/O/sub 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/sub 2/O/sub 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.

  16. Inflammation, oxidative DNA damage, and carcinogenesis.

    PubMed Central

    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 thought 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. Many studies support the multistep nature of carcinogenesis, and a significant amount of evidence indicates that more than one genetic event is necessary for neoplastic transformation. Selective growth stimulation of initiated cells by TPA does not explain how further genetic events may occur by chronic exposure to this nongenotoxic agent. We 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 H2O2 and oxidized lipid products. Furthermore, macrophage populations that release both H2O2 and metabolites of arachidonic acid (AA) are more efficient at inducing oxidative DNA damage in surrounding cells than populations which only release H2O2 or metabolites of AA. In vivo studies demonstrated that SENCAR mice, which are sensitive to promotion by TPA, have a more intense inflammatory reaction in skin than C57LB/6 mice, which are resistant to promotion by TPA. In addition, macrophages from SENCAR mice release more H2O2 and metabolites of AA, and induce more oxidative DNA damage in cocultured cells than macrophages from C57LB/6 mice.(ABSTRACT TRUNCATED AT 250 WORDS) Images FIGURE 8. A FIGURE 8. B PMID:3129286

  17. Oxidant damage during and after spaceflight

    NASA Technical Reports Server (NTRS)

    Stein, T. P.; Leskiw, M. J.

    2000-01-01

    The objectives of this study were to assess oxidant damage during and after spaceflight and to compare the results against bed rest with 6 degrees head-down tilt. We measured the urinary excretion of the F(2) isoprostane, 8-iso-prostaglandin (PG) F(2alpha), and 8-oxo-7,8-dihydro-2 deoxyguanosine (8-OH DG) before, during, and after long-duration spaceflight (4-9 mo) on the Russian space station MIR, short-duration spaceflight on the shuttle, and 17 days of bed rest. Sample collections on MIR were obtained between 88 and 186 days in orbit. 8-iso-PGF(2alpha) and 8-OH DG are markers for oxidative damage to membrane lipids and DNA, respectively. Data are mean +/- SE. On MIR, isoprostane levels were decreased inflight (96. 9 +/- 11.6 vs. 76.7 +/- 14.9 ng. kg(-1). day(-1), P < 0.05, n = 6) due to decreased dietary intake secondary to impaired thermoregulation. Isoprostane excretion was increased postflight (245.7 +/- 55.8 ng. kg(-1). day(-1), P < 0.01). 8-OH DG excretion was unchanged with spaceflight and increased postflight (269 +/- 84 vs 442 +/- 180 ng. kg(-1). day(-1), P < 0.05). On the shuttle, 8-OH DG excretion was unchanged in- and postflight, but 8-iso-PGF(2alpha) excretion was decreased inflight (15.6 +/- 4.3 vs 8.0 +/- 2.7 ng. kg(-1). day(-1), P < 0.05). No changes were found with bed rest, but 8-iso-PGF(2alpha) was increased during the recovery phase (48.9 +/- 23.0 vs 65.4 +/- 28.3 ng. kg(-1). day(-1), P < 0.05). The changes in isoprostane production were attributed to decreased production of oxygen radicals from the electron transport chain due to the reduced energy intake inflight. The postflight increases in the excretion of the products of oxidative damage were attributed to a combination of an increase in metabolic activity and the loss of some host antioxidant defenses inflight. We conclude that 1) oxidative damage was decreased inflight, and 2) oxidative damage was increased postflight.

  18. Oxidative and non-oxidative DNA damage and cardiovascular disease.

    PubMed

    Malik, Qudsia; Herbert, Karl E

    2012-04-01

    Evidence for the association of DNA damage with cardiovascular disease has been obtained from in vitro cell culture models, experimental cardiovascular disease and analysis of samples obtained from humans with disease. There is general acceptance that several factors associated with the risk of developing cardiovascular disease cause oxidative damage to DNA in cell culture models with both nuclear and mitochondrial DNA as targets. Moreover, evidence obtained over the past 10 years points to a possible mechanistic role for DNA damage in experimental atherosclerosis culminating in recent studies challenging the assumption that DNA damage is merely a biomarker of the disease process. This kind of mechanistic insight provides a renewed impetus for further studies in this area.

  19. Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model.

    PubMed

    Cai, Jing; Cao, Shenglong; Chen, Jingyin; Yan, Feng; Chen, Gao; Dai, Yuying

    2015-07-23

    This study aimed to investigate the therapeutic effect of progesterone on acute brain injury after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced in male Sprague-Dawley rats (n=72) by endovascular perforation. Progesterone (8 mg/kg or 16 mg/kg) was administered to rats at 1, 6, and 12h after SAH. Mortality, neurologic deficits, cell apoptosis, expression of apoptotic markers, the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were assayed at 24h after experimental SAH. Mortality, cell apoptosis and the expression of caspase-3 were decreased, and improved neurological function was observed in the progesterone-treated SAH rats. Further, exploration demonstrated that progesterone significantly reduced the ratio of Bax/Bcl-2 and attenuated the release of cytochrome c from mitochondria. Progesterone also induced anti-oxidative effects by elevating the activity of SOD and decreasing MDA content after SAH. Furthermore, dose-response relationships for progesterone treatment were observed, and high doses of progesterone enhanced the neuroprotective effects. Progesterone treatment could alleviate acute brain injury after SAH by inhibiting cell apoptosis and decreasing damage due to oxidative stress. The mechanism involved in the anti-apoptotic effect was related to the mitochondrial pathway. These results indicate that progesterone possesses the potential to be a novel therapeutic agent for the treatment of acute brain injury after SAH.

  20. Profiling oxidative DNA damage: effects of antioxidants.

    PubMed

    Box, Harold C; Patrzyc, Helen B; Budzinski, Edwin E; Dawidzik, Jean B; Freund, Harold G; Zeitouni, Nathalie C; Mahoney, Martin C

    2012-11-01

    The goal of this research was to determine whether antioxidant usage could be correlated with changes in DNA damage levels. Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) was used to simultaneously measure five different oxidatively-induced base modifications in the DNA of WBC. Measurements of the five modifications were made before and after an 8-week trial during which participants took the SU.VI.MAX supplement. Levels of the five DNA modifications were compared among different groupings: users versus non-users of antioxidant supplements, before versus after the supplement intervention and men versus women. The statistical significance of differences between groups was most significant for pyrimidine base modifications and the observed trends reflect trends reported in epidemiological studies of antioxidant usage. A combination of modifications derived from pyrimidine bases is suggested as a superior indicator of oxidative stress.

  1. Sodium chloride alleviates cadmium toxicity by reducing nitric oxide accumulation in tobacco.

    PubMed

    Zhang, Binglin; Shang, Shenghua; Jabben, Zahra; Zhang, Guoping

    2014-12-01

    Nitric oxide (NO) is involved in regulating the response of plants to Cd toxicity. In this study, we examined possible involvement of NO in the alleviation of Cd toxicity by NaCl in tobacco plants. Two independent experiments were conducted to investigate the changes of NO accumulation and Cd concentration in tobacco plants after the addition of a NO donor, sodium nitroprusside dehydrate (SNP), or a NO inhibitor, nitro-l-arginine methyl ester (l-NAME) in the solution containing NaCl and Cd. NO accumulation in tobacco roots was enhanced when plants were exposed to Cd, but reduced in the treatments of NaCl or l-NAME. NO production was not enhanced even when SNP (NO donor) was added to the solution containing Cd and NaCl. Root number was reduced in plants exposed to Cd, and increased by the addition of NaCl and reduced by the addition of SNP. Addition of NaCl or l-NAME to the Cd-containing solution reduced Cd concentration in plant tissues, with l-NAME having a more dramatic effect. It can be concluded that alleviation of Cd toxicity by NaCl contributed to reduction of NO accumulation in plants.

  2. Alleviating inequality in climate policy costs: an integrated perspective on mitigation, damage and adaptation

    NASA Astrophysics Data System (ADS)

    De Cian, E.; Hof, A. F.; Marangoni, G.; Tavoni, M.; van Vuuren, D. P.

    2016-07-01

    Equity considerations play an important role in international climate negotiations. While policy analysis has often focused on equity as it relates to mitigation costs, there are large regional differences in adaptation costs and the level of residual damage. This paper illustrates the relevance of including adaptation and residual damage in equity considerations by determining how the allocation of emission allowances would change to counteract regional differences in total climate costs, defined as the costs of mitigation, adaptation, and residual damage. We compare emission levels resulting from a global carbon tax with two allocations of emission allowances under a global cap-and-trade system: one equating mitigation costs and one equating total climate costs as share of GDP. To account for uncertainties in both mitigation and adaptation, we use a model-comparison approach employing two alternative modeling frameworks with different damage, adaptation cost, and mitigation cost estimates, and look at two different climate goals. Despite the identified model uncertainties, we derive unambiguous results on the change in emission allowance allocation that could lessen the unequal distribution of adaptation costs and residual damages through the financial transfers associated with emission trading.

  3. Geraniol alleviates diabetic cardiac complications: Effect on cardiac ischemia and oxidative stress.

    PubMed

    El-Bassossy, Hany M; Ghaleb, Hanna; Elberry, Ahmed A; Balamash, Khadijah S; Ghareib, Salah A; Azhar, Ahmad; Banjar, Zainy

    2017-04-01

    The present study was planned to assess the possible protective effect of geraniol on cardiovascular complications in an animal model with diabetes. Diabetes was induced in rats by a single streptozotocin injection. In the treated group, geraniol (150mgkg(-1)day(-1)) was administered orally starting from the 15th day after induction of diabetes, and ending after 7 weeks; diabetic control rats were given vehicle for the same period. At the end of the study, cardiac contractility was assessed by using a Millar microtip catheter in anesthetised rats, and cardiac conductivity determined by a surface ECG. Serum levels of glucose, cholesterol, triglyceride and adiponectin as well as urine 8-isoprostane were determined. In addition, cardiac superoxide dismutase (SOD) and catalase activity were measured. Geraniol administration significantly alleviated the attenuated cardiac systolic function associated with diabetes as indicated by inhibiting the decrease in the rate of rise (dP/dtmax) in ventricular pressure and the increase in systolic duration observed in diabetic rats. In addition, geraniol alleviated impaired diastolic function as shown by inhibiting the decrease in the rate of fall (dP/dtmin) in ventricular pressure and increased isovolumic relaxation constant (Tau) observed in diabetic rats. ECG recordings showed that geraniol prevented any increase in QTc and T-peak-T-end intervals, and markers of LV ischemia and arrhythmogenesis, seen in diabetic animals. Geraniol suppressed the exaggerated oxidative stress as evidenced by preventing the increase in 8-isoprotane. In diabetic heart tissue, geraniol prevented the inhibition in catalase activity but did not affect the heart SOD. Geraniol partially reduced hyperglycemia, prevented the hypercholesterolemia, but did not affect the serum level of adiponectin in diabetic animals. Results obtained in this study suggest that geraniol provides a potent protective effect against cardiac dysfunction induced by diabetes. This

  4. Alleviative effect of myricetin on ochratoxin A-induced oxidative stress in rat renal cortex: histological and biochemical study.

    PubMed

    El-Haleem, Manal R Abdel; Kattaia, Asmaa A A; El-Baset, Samia A Abdel; Mostafa, Heba El Sayed

    2016-04-01

    Ochratoxins (OTA) are secondary metabolites of Aspergillus and Penicillium. The detoxification of OTA has been of major interest due to its widespread threat to human health. We aimed to investigate the possible alleviative effect of myricetin (MYR) against OTA-induced damage in renal cortex of rats. Thirty adult male albino rats were randomized into five equal groups: control (untreated), vehicle control (0.5 ml corn oil/day including dimethylsulfoxide [DMSO]), MYR (100 mg MYR/kg b.w./day in distilled water), OTA (0.5 mg OTA/kg b.w./day; dissolved in 10% DMSO and then corn oil) and OTA + MYR group (received OTA and MYR at similar doses). All treatments were given by oral gavage for 2 weeks. At the end of the experiment, renal cortices were processed for light and electron microscope examinations. Immunohistochemical staining for localization of proliferating cell nuclear antigen (PCNA), p53 and transforming growth factor beta 1 (TGF-β1) was carried out. Biochemical analysis of tissue glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress. OTA administration induced deleterious renal injury evidenced by the structural and ultra-structural changes. Immunohistochemical expression of p53, PCNA and TGF-β1 were significantly up regulated compared with control. Alterations in antioxidant parameters supported that oxidative stress was one of the mechanisms involved in OTA toxicity. On the contrary, co-administration of MRY partially ameliorated OTA-induced renal injury. We suggest the potential effectiveness of MYR to counteract OTA-induced toxic oxidative stress on the renal cortex.

  5. Acrylonitrile-induced oxidative DNA damage in rat astrocytes.

    PubMed

    Pu, Xinzhu; Kamendulis, Lisa M; Klaunig, James E

    2006-10-01

    Chronic administration of acrylonitrile results in a dose-related increase in astrocytomas in rat brain, but the mechanism of acrylonitrile carcinogenicity is not fully understood. The potential of acrylonitrile or its metabolites to induce direct DNA damage as a mechanism for acrylonitrile carcinogenicity has been questioned, and recent studies indicate that the mechanism involves the induction of oxidative stress in rat brain. The present study examined the ability of acrylonitrile to induce DNA damage in the DI TNC1 rat astrocyte cell line using the alkaline Comet assay. Oxidized DNA damage also was evaluated using formamidopyrimidine DNA glycosylase treatment in the modified Comet assay. No increase in direct DNA damage was seen in astrocytes exposed to sublethal concentrations of acrylonitrile (0-1.0 mM) for 24 hr. However, acrylonitrile treatment resulted in a concentration-related increase in oxidative DNA damage after 24 hr. Antioxidant supplementation in the culture media (alpha-tocopherol, (-)-epigallocathechin-3 gallate, or trolox) reduced acrylonitrile-induced oxidative DNA damage. Depletion of glutathione using 0.1 mM DL-buthionine-[S,R]-sulfoximine increased acrylonitrile-induced oxidative DNA damage (22-46%), while cotreatment of acrylonitrile with 2.5 mM L-2-oxothiazolidine-4-carboxylic acid, a precursor for glutathione biosynthesis, significantly reduced acrylonitrile-induced oxidative DNA damage (7-47%). Cotreatment of acrylonitrile with 0.5 mM 1-aminobenzotriazole, a suicidal inhibitor of cytochrome P450, prevented the oxidative DNA damage produced by acrylonitrile. Cyanide (0.1-0.5 mM) increased oxidative DNA damage (44-160%) in astrocytes. These studies demonstrate that while acrylonitrile does not directly damage astrocyte DNA, it does increase oxidative DNA damage. The oxidative DNA damage following acrylonitrile exposure appears to arise mainly through the P450 metabolic pathway; moreover, glutathione depletion may contribute to the

  6. Alleviation of iron induced oxidative stress by the grape fruit flavanone naringin in vitro.

    PubMed

    Jagetia, Ganesh Chandra; Reddy, Tiyagura Koti

    2011-04-25

    Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. The protective effect of naringin, a grape fruit flavanone, was studied in iron overloaded isolated mouse liver mitochondria, where the isolated mitochondrial fraction was incubated with various concentrations of naringin before ferric ion loading. Iron overloading of mitochondrial fraction resulted in an increase in lipid peroxidation, protein oxidation, and DNA damage, whereas iron overload reduced the glutathione (GSH) concentration, glutathione-S-transferase (GST), glutathione peroxidase (GSHPx), catalase and superoxide dismutase (SOD) activities. Pretreatment of mitochondrial fraction with naringin inhibited iron-induced lipid peroxidation, protein oxidation, and DNA damage. Conversely, naringin supplementation arrested iron-induced depletion in the GSH contents, GSHPx, GST, SOD and catalase activities significantly. Ferric iron reduction assay revealed that naringin could not reduce ferric iron into ferrous iron indicating that it did not exhibit prooxidant activity. Iron free coordination site assay indicated that naringin was unable to occupy all the active sites of iron indicating that naringin did not completely chelate iron. Our study demonstrates that naringin was able to share the burden of endogenous oxidants by inhibiting the iron-induced depletion of all important antioxidant enzymes as well as GSH and may act as a good antioxidant.

  7. Polyhydroxyfullerene Binds Cadmium Ions and Alleviates Metal-Induced Oxidative Stress in Saccharomyces cerevisiae

    PubMed Central

    Pradhan, Arunava; Pinheiro, José Paulo; Seena, Sahadevan; Pascoal, Cláudia

    2014-01-01

    The water-soluble polyhydroxyfullerene (PHF) is a functionalized carbon nanomaterial with several industrial and commercial applications. There have been controversial reports on the toxicity and/or antioxidant properties of fullerenes and their derivatives. Conversely, metals have been recognized as toxic mainly due to their ability to induce oxidative stress in living organisms. We investigated the interactive effects of PHF and cadmium ions (Cd) on the model yeast Saccharomyces cerevisiae by exposing cells to Cd (≤5 mg liter−1) in the absence or presence of PHF (≤500 mg liter−1) at different pHs (5.8 to 6.8). In the absence of Cd, PHF stimulated yeast growth up to 10.4%. Cd inhibited growth up to 79.7%, induced intracellular accumulation of reactive oxygen species (ROS), and promoted plasma membrane disruption in a dose- and pH-dependent manner. The negative effects of Cd on growth were attenuated by the presence of PHF, and maximum growth recovery (53.8%) was obtained at the highest PHF concentration and pH. The coexposure to Cd and PHF decreased ROS accumulation up to 36.7% and membrane disruption up to 30.7% in a dose- and pH-dependent manner. Two mechanisms helped to explain the role of PHF in alleviating Cd toxicity to yeasts: PHF decreased Cd-induced oxidative stress and bound significant amounts of Cd in the extracellular medium, reducing its bioavailability to the cells. PMID:25038095

  8. Aminoguanidine alleviated MMA-induced impairment of cognitive ability in rats by downregulating oxidative stress and inflammatory reaction.

    PubMed

    Li, Qiliang; Song, Wenqi; Tian, Ze; Wang, Peichang

    2017-02-13

    Methylmalonic acidemia (MMA) is the most common organic acidemia in childhood. Many "treated" patients continued to display various degrees of mental retardation and psychomotor delay, which could be caused by brain damage from elevated oxidative stress. Aminoguanidine (AG), a synthetic antioxidant, was tested in a MMA rat model for its potential therapeutic effects on memory impairment. The effects of AG on MMA-induced cognitive impairment in Wistar rats were evaluated with Morris Water Maze. The levels of nerve cell apoptosis and microglial activation were investigated to illustrate the mechanisms of the improvement of cognition with AG treatment in MMA rats. To further explore the mechanism of neuroprotection induced by AG, several biomarkers including free radicals and inflammatory cytokines in the hippocampus were quantified. The results showed that the rats treated with AG exhibited better neurological behavior performances than MMA model rats. The AG-treated rats had a decreased level of apoptosis of the hippocampal neurons, which could be the structural basis of the observed neural behavior protection. In addition, AG treatment significantly inhibited the activation of microglia. The AG-treated rats had decreased levels of IL-1β, IL-6, TNF-α, NO, malonaldehyde and iNOS activities in the hippocampus. The level of glutathione and superoxide dismutase activity in the hippocampus of the AG-treated rats increased significantly. In conclusion, AG could alleviate the MMA-induced cognitive impairment via down-regulating of oxidative stress and inflammatory reaction and provide a basis as a therapeutic potential against MMA-induced cognitive impairment.

  9. Melatonin alleviates lung damage induced by the chemical warfare agent nitrogen mustard.

    PubMed

    Ucar, Muharrem; Korkmaz, Ahmet; Reiter, Russel J; Yaren, Hakan; Oter, Sükrü; Kurt, Bülent; Topal, Turgut

    2007-09-10

    The cytotoxic mechanism of mustards has not been fully elucidated; recently, we reported that reactive oxygen species, nitric oxide [produced by inducible nitric oxide synthase (iNOS)] and peroxynitrite are involved in the pathogenesis and responsible for mustard-induced toxicity. Melatonin, a potent antioxidant molecule, acts as an iNOS inhibitor and a peroxynitrite scavenger. Using the prototypic nitrogen mustard (mechlorethamine/HN2) as a model and based on its known cytotoxic mechanisms, the present study was performed to test melatonin for its capability in protecting the lungs of injured male Wistar rats. Lung mustard toxicity was induced via an intratracheally injection of HN2 (0.5mg/kg) dissolved in saline (100microl). Control animals were injected the same amount of saline only. Melatonin was administered intraperitoneally with two different doses (20mg/kg or 40mg/kg) beginning 1h before HN2 application and continued every 12h for six replications. Forty-eight hours after the last melatonin injection, the animals were sacrificed and their lungs were taken for further assay, i.e., malondialdehyde (MDA) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx) and iNOS activity. Additionally their urine was collected for nitrite-nitrate (NO(x)) analysis. HN2 injection caused increased iNOS activity and MDA levels in lung tissue and NO(x) values in urine; lung GPx activity was significantly depressed. Melatonin restored all of these oxidative and nitrosative stress markers in a dose-dependent manner. In conclusion, the results of study provide evidence that melatonin may have the ability to reduce mustard-induced toxicity in the lungs.

  10. DNA damage in Fabry patients: An investigation of oxidative damage and repair.

    PubMed

    Biancini, Giovana Brondani; Moura, Dinara Jaqueline; Manini, Paula Regina; Faverzani, Jéssica Lamberty; Netto, Cristina Brinckmann Oliveira; Deon, Marion; Giugliani, Roberto; Saffi, Jenifer; Vargas, Carmen Regla

    2015-06-01

    Fabry disease (FD) is a lysosomal storage disorder associated with loss of activity of the enzyme α-galactosidase A. In addition to accumulation of α-galactosidase A substrates, other mechanisms may be involved in FD pathophysiology, such as inflammation and oxidative stress. Higher levels of oxidative damage to proteins and lipids in Fabry patients were previously reported. However, DNA damage by oxidative species in FD has not yet been studied. We investigated basal DNA damage, oxidative DNA damage, DNA repair capacity, and reactive species generation in Fabry patients and controls. To measure oxidative damage to purines and pyrimidines, the alkaline version of the comet assay was used with two endonucleases, formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). To evaluate DNA repair, a challenge assay with hydrogen peroxide was performed. Patients presented significantly higher levels of basal DNA damage and oxidative damage to purines. Oxidative DNA damage was induced in both DNA bases by H2O2 in patients. Fabry patients presented efficient DNA repair in both assays (with and without endonucleases) as well as significantly higher levels of oxidative species (measured by dichlorofluorescein content). Even if DNA repair be induced in Fabry patients (as a consequence of continuous exposure to oxidative species), the repair is not sufficient to reduce DNA damage to control levels.

  11. Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.

    PubMed

    Ii, Hiromi; Yokoyama, Naoki; Yoshida, Shintaro; Tsutsumi, Kae; Hatakeyama, Shinji; Sato, Takashi; Ishihara, Keiichi; Akiba, Satoshi

    2009-12-01

    Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA(2)-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA(2)-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA(2)-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA(2)-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA(2)-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E(2), which has a fat storage effect, was lower in IVA-PLA(2)-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA(2) alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA(2) metabolites, such as prostaglandin E(2). IVA-PLA(2) could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.

  12. Cerium oxide nanoparticles alleviate oxidative stress and decreases Nrf-2/HO-1 in D-GALN/LPS induced hepatotoxicity.

    PubMed

    Hashem, Reem M; Rashd, Laila A; Hashem, Khalid S; Soliman, Hatem M

    2015-07-01

    Translocation of the master regulator of antioxidant-response element-driven antioxidant gene, nuclear factor erythroid 2 (Nrf-2) from the cytoplasm into the nucleus and triggering the transcription of hemoxygenase-1 (HO-1) to counteract the oxidative stress is a key feature in D-galactoseamine and lipopolysaccharide (D-GALN/LPS) induced hepatotoxicity. We mainly aimed to study the effect of cerium oxide (CeO2) nanoparticles on Nrf-2/HO-1 pathway whereas; it has previously shown to have an antioxidant effect in liver models. Administration of CeO2 nanoparticles significantly decreased the translocation of the cytoplasmic Nrf-2 with a concomitant decrement in the gene expression of HO-1 as it reveals a powerful antioxidative effect as indicated by the significant increase in the levels of glutathione (GSH), glutathione peroxidase (GPX1), glutathione reductase (GR), superoxide dismutase (SOD) and catalase. In synchronization, a substantial decrement in the levels of inducible nitric oxide synthase (iNOS), TBARS and percentage of DNA fragmentation was established. These results were confirmed by histopathology examination which showed a severe degeneration, haemorrhages, widened sinusoids and focal leukocyte infiltration in D-GALN/LPS treatment and these features were alleviated with CeO2 administration. In conclusion, CeO2 is a potential antioxidant that can effectively decrease the translocation of the cytoplasmic Nrf-2 into the nucleus and decrease HO-1 in D-GALN/LPS induced hepatotoxicity.

  13. Plant Leucine Aminopeptidases Moonlight as Molecular Chaperones to Alleviate Stress-induced Damage*

    PubMed Central

    Scranton, Melissa A.; Yee, Ashley; Park, Sang-Youl; Walling, Linda L.

    2012-01-01

    Leucine aminopeptidases (LAPs) are present in animals, plants, and microbes. In plants, there are two classes of LAPs. The neutral LAPs (LAP-N and its orthologs) are constitutively expressed and detected in all plants, whereas the stress-induced acidic LAPs (LAP-A) are expressed only in a subset of the Solanaceae. LAPs have a role in insect defense and act as a regulator of the late branch of wound signaling in Solanum lycopersicum (tomato). Although the mechanism of LAP-A action is unknown, it has been presumed that LAP peptidase activity is essential for regulating wound signaling. Here we show that plant LAPs are bifunctional. Using three assays to monitor protein protection from heat-induced damage, it was shown that the tomato LAP-A and LAP-N and the Arabidopsis thaliana LAP1 and LAP2 are molecular chaperones. Assays using LAP-A catalytic site mutants demonstrated that LAP-A chaperone activity was independent of its peptidase activity. Furthermore, disruption of the LAP-A hexameric structure increased chaperone activity. Together, these data identify a new class of molecular chaperones and a new function for the plant LAPs as well as suggesting new mechanisms for LAP action in the defense of solanaceous plants against stress. PMID:22493451

  14. Plant leucine aminopeptidases moonlight as molecular chaperones to alleviate stress-induced damage.

    PubMed

    Scranton, Melissa A; Yee, Ashley; Park, Sang-Youl; Walling, Linda L

    2012-05-25

    Leucine aminopeptidases (LAPs) are present in animals, plants, and microbes. In plants, there are two classes of LAPs. The neutral LAPs (LAP-N and its orthologs) are constitutively expressed and detected in all plants, whereas the stress-induced acidic LAPs (LAP-A) are expressed only in a subset of the Solanaceae. LAPs have a role in insect defense and act as a regulator of the late branch of wound signaling in Solanum lycopersicum (tomato). Although the mechanism of LAP-A action is unknown, it has been presumed that LAP peptidase activity is essential for regulating wound signaling. Here we show that plant LAPs are bifunctional. Using three assays to monitor protein protection from heat-induced damage, it was shown that the tomato LAP-A and LAP-N and the Arabidopsis thaliana LAP1 and LAP2 are molecular chaperones. Assays using LAP-A catalytic site mutants demonstrated that LAP-A chaperone activity was independent of its peptidase activity. Furthermore, disruption of the LAP-A hexameric structure increased chaperone activity. Together, these data identify a new class of molecular chaperones and a new function for the plant LAPs as well as suggesting new mechanisms for LAP action in the defense of solanaceous plants against stress.

  15. Type-dependent oxidative damage in frontotemporal lobar degeneration: cortical astrocytes are targets of oxidative damage.

    PubMed

    Martínez, Anna; Carmona, Margarita; Portero-Otin, Manuel; Naudí, Alba; Pamplona, Reinald; Ferrer, Isidre

    2008-12-01

    Oxidative injury and stress responses are common features of many neurodegenerative diseases. To assess oxidative stress responses in frontotemporal lobar degeneration (FTLD), we identified increased 4-hydroxynonenal (HNE) adducts using gel electrophoresis and Western blotting in frontal cortex samples in 6 of 6 cases of FTLD with the P301L mutation in the tau gene (FTLD-tau), in 3 of 10 cases with tau-negative ubiquitin-immunoreactive inclusions, and in 2 of 3 cases associated with motor neuron disease. Selectively increased lipoxidation-derived protein damage associated with altered membrane unsaturation and fatty acid profiles was verified by mass spectrometry in FTLD-tau and FTLD associated with motor neuron disease. All FTLD-tau and most cases with increased HNE-positive bands had marked astrocytosis as determined by glial fibrillary acidic protein (GFAP) immunohistochemistry and increased GFAP expression on Western blotting; 2 FTLD cases with tau-negative ubiquitin-immunoreactive inclusions and with increased GFAP expression did not have increased HNE adducts. Bidimensional gel electrophoresis, Western blotting, in-gel digestion, and mass spectrometry identified GFAP as a major target of lipoxidation in all positive cases; confocal microscopy revealed colocalization of HNE and GFAP in cortical astrocytes, superoxide dismutase 1 in astrocytes, and superoxide dismutase 2 in astrocytes and neurons in all FTLD types. Thus, in FTLD, there is variable disease-dependent oxidative damage that is prominent in FTLD-tau, astrocytes are targets of oxidative damage, and GFAP is a target of lipoxidation. Astrocytes are, therefore, crucial elements of oxidative stress responses in FTLD.

  16. Sperm DNA oxidative damage and DNA adducts

    PubMed Central

    Jeng, Hueiwang Anna; Pan, Chih-Hong; Chao, Mu-Rong; Lin, Wen-Yi

    2015-01-01

    The objective of this study was to investigate DNA damage and adducts in sperm from coke oven workers who have been exposed to polycyclic aromatic hydrocarbons. A longitudinal study was conducted with repeated measurements during spermatogenesis. Coke-oven workers (n=112) from a coke-oven plant served the PAH-exposed group, while administrators and security personnel (n=67) served the control. Routine semen parameters (concentration, motility, vitality, and morphology) were analyzed simultaneously; the assessment of sperm DNA integrity endpoints included DNA fragmentation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGuo). The degree of sperm DNA fragmentation was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and sperm chromatin structure assay (SCSA). The PAH-exposed group had a significant increase in bulky DNA adducts and 8-oxo-dGuo compared to the control subjects (Ps = 0.002 and 0.045, respectively). Coke oven workers' percentages of DNA fragmentation and denaturation from the PAH-exposed group were not significantly different from those of the control subjects (Ps = 0.232 and 0.245, respectively). Routine semen parameters and DNA integrity endpoints were not correlated. Concentrations of 8-oxo-dGuo were positively correlated with percentages of DNA fragmentation measured by both TUNEL and SCSA (Ps = 0.045 and 0.034, respectively). However, the concentrations of 8-oxo-dGuo and percentages of DNA fragmentation did not correlate with concentrations of bulky DNA adducts. In summary, coke oven workers with chronic exposure to PAHs experienced decreased sperm DNA integrity. Oxidative stress could contribute to the degree of DNA fragmentation. Bulky DNA adducts may be independent of the formation of DNA fragmentation and oxidative adducts in sperm. Monitoring sperm DNA integrity is recommended as a part of the process of assessing the impact of occupational and environmental toxins on

  17. Phosphorus improves arsenic phytoremediation by Anadenanthera peregrina by alleviating induced oxidative stress.

    PubMed

    Gomes, M P; Carvalho, M; Carvalho, G S; Marques, T C L L S M; Garcia, Q S; Guilherme, L R G; Soares, A M

    2013-01-01

    Due to similarities in their chemical behaviors, studies examining interactions between arsenic (As)--in special arsenate--and phosphorus (P) are important for better understanding arsenate uptake, toxicity, and accumulation in plants. We evaluated the effects of phosphate addition on plant biomass and on arsenate and phosphate uptake by Anadenanthera peregrina, an important Brazilian savanna legume. Plants were grown for 35 days in substrates that received combinations of 0, 10, 50, and 100 mg kg(-1) arsenate and 0, 200, and 400 mg kg(-1) phosphate. The addition of P increased the arsenic-phytoremediation capacity of A. peregrina by increasing As accumulation, while also alleviating As-induced oxidative stress. Arsenate phytotoxicity in A. peregrina is due to lipid peroxidation, but not hydrogen peroxide accumulation. Added P also increased the activity of important reactive oxygen species-scavenging enzymes (catalase and ascorbate peroxidase) that help prevent lipid peroxidation in leaves. Our findings suggest that applying P represents a feasible strategy for more efficient As phytoremediation using A. peregrina.

  18. Isorhamnetin-3-glucoside alleviates oxidative stress and opacification in selenite cataract in vitro.

    PubMed

    Devi, V Gayathri; Rooban, B N; Sasikala, V; Sahasranamam, V; Abraham, Annie

    2010-09-01

    Oxidative stress has long been recognized as an important mediator in the pathogenesis of cataract and the goal of this study was to determine the efficacy of isorhamnetin-3-glucoside (IR3G) in alleviating the toxicity induced by sodium selenite in in vitro culture condition. IR3G is the bioactive flavonoid isolated and characterized from the leaves of Cochlospermum religiosum. Enucleated rat lenses were maintained in organ culture containing M-199 medium alone (G-I), supplemented with 0.1 mM selenite (G-II) and selenite + 25 microg/ml IR3G (G-III). Treatment to G-III was from the second to fifth day while selenite administration to G-II & III was done on the third day. The antioxidant potential of the compound was assessed by Cu(2+) induced lipoprotein diene formation and superoxide scavenging assays. Morphological examination of the lenses also gave a supporting data. Antioxidant enzymes-superoxide dismutase (SOD), catalase and concentration of reduced glutathione (GSH) were significantly lower, while TBARS showed an increase in G-II than that in G-III and G-I lenses. Activity of Ca(2+)-ATPase was decreased and level of calcium was increased in G-II than G-III and G-I lenses. These data suggest that IR3G is able to significantly retard selenite cataract in vitro by virtue of its antioxidant property.

  19. Modulating the p66shc signaling pathway with protocatechuic acid protects the intestine from ischemia-reperfusion injury and alleviates secondary liver damage.

    PubMed

    Ma, Lingfei; Wang, Guangzhi; Chen, Zhao; Li, Zhenlu; Yao, Jihong; Zhao, Haidong; Wang, Shu; Ma, Zhenhai; Chang, Hong; Tian, Xiaofeng

    2014-01-01

    Intestinal ischemia-reperfusion (I/R) injury is a serious clinical pathophysiological process that may result in acute local intestine and remote liver injury. Protocatechuic acid (PCA), which has been widely studied as a polyphenolic compound, induces expression of antioxidative genes that combat oxidative stress and cell apoptosis. In this study, we investigated the effect of PCA pretreatment for protecting intestinal I/R-induced local intestine and remote liver injury in mice. Intestinal I/R was established by superior mesenteric artery occlusion for 45 min followed by reperfusion for 90 min. After the reperfusion period, PCA pretreatment markedly alleviated intestine and liver injury induced by intestinal I/R as indicated by histological alterations, decreases in serological damage parameters and nuclear factor-kappa B and phospho-foxo3a protein expression levels, and increases in glutathione, glutathione peroxidase, manganese superoxide dismutase protein expression, and Bcl-xL protein expression in the intestine and liver. These parameters were accompanied by PCA-induced adaptor protein p66shc suppression. These results suggest that PCA has a significant protective effect in the intestine and liver following injury induced by intestinal I/R. The protective effect of PCA may be attributed to the suppression of p66shc and the regulation of p66shc-related antioxidative and antiapoptotic factors.

  20. Endogenous nitric oxide mediates alleviation of cadmium toxicity induced by calcium in rice seedlings.

    PubMed

    Zhang, Long; Chen, Zhen; Zhu, Cheng

    2012-01-01

    The effect of calcium chloride (CaCl2) on rice seedling growth under cadmium chloride (CdCl2) stress, as well as the possible role of endogenous nitric oxide (NO) in this process, was studied. The growth of rice seedlings was seriously inhibited by CdCl2, and the inhibition was significantly mitigated by CaCl2. However, hemoglobin (Hb) and 2-(4-carboxyphenyl)-4, 4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) weakened the promotion effect of CaCl2. The results of NO fluorescence localization suggest that growth accelerated by CaCl2 might be associated with elevated NO levels. The content of Cd, protein thiols (PBT), and nonprotein thiols (NPT) in cell walls, cell organelles, and soluble fractions, respectively, of rice seedlings decreased considerably in the presence of CaCl2, whereas the content of pectin, hemicellulose 1 (HC1), and hemicellulose 2 (HC2) increased significantly. Elimination of endogenous NO in Cd+Ca treatment could promote the transportation of Cd2+ to cell organelles and soluble fractions and increase the content of NPT and PBT in leaves. In addition, transportation of Cd2+ to cell organelles and soluble fractions was retarded in roots, the content of NPT increased, and the content of PBT decreased. With elimination of endogenous NO in Cd+Ca treatment, the content of pectin, HC1, and HC2 decreased significantly. Thus, Ca may alleviate Cd toxicity via endogenous NO with variation in the levels of NPT, PBT, and matrix polysaccharides.

  1. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.

    PubMed

    Kalghatgi, Sameer; Spina, Catherine S; Costello, James C; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S; Collins, James J

    2013-07-03

    Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics-quinolones, aminoglycosides, and β-lactams-cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic-induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.

  2. Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

    PubMed Central

    Costello, James C.; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S.; Collins, James J.

    2013-01-01

    Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-L-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people. PMID:23825301

  3. Potential role of Saudi red propolis in alleviating lung damage induced by methicillin resistant Staphylococcus aureus virulence in rats.

    PubMed

    Saddiq, Amna Ali; Mohamed, Azza Mostafa

    2016-07-01

    The aim of this study was to explore the protective impact of aqueous extract of Saudi red propolis against rat lung damage induced by the pathogenic bacteria namely methicillin resistant Staphylococcus aureus (MRSA) ATCC 6538 strain. Infected rats were received a single intraperitoneal (i.p.) injection of bacterial suspension at a dose of 1 X 10(6) CFU / 100g body weight. Results showed that oral administration of an aqueous extract of propolis (50mg/100g body weight) daily for two weeks to infected rats simultaneously with bacterial infection, effectively ameliorated the alteration of oxidative stress biomarker, malondialdehyde (MDA), as well as the antioxidant markers, glutathione peroxidase (GPx) and superoxide dismutase (SOD), in lungs of infected rats compared with infected untreated ones. Also, the used propolis extract successfully modulated the alterations in proinflammatory mediators, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in serum. In addition, the propolis extract successfully modulated the oxidative DNA damage and the apoptosis biomarker, caspase 3, in lungs of S aureus infected rats compared with infected untreated animals. The biochemical results were supported by histo-pathological observation of lung tissues. In conclusion, the beneficial prophylactic role of the aqueous extract of Saudi red propolis against lung damage induced by methicillin resistant S aureus may be related to the antioxidant, anti-inflammatory, immunomodulatory and antiapoptosis of its active constituents.

  4. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

    PubMed Central

    Xu, Dunquan; Li, Yan; Zhang, Bo; Wang, Yanxia; Liu, Yi; Luo, Ying; Niu, Wen; Dong, Mingqing; Liu, Manling; Dong, Haiying; Zhao, Pengtao; Li, Zhichao

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development. Sprague-Dawley rats were challenged by hypoxia exposure for 28 days to mimic hypoxic pulmonary hypertension along with treating resveratrol (40 mg/kg/day). Hemodynamic and pulmonary pathomorphology data were then obtained, and the anti-proliferation effect of resveratrol was determined by in vitro assays. The anti-inflammation and anti-oxidative effects of resveratrol were investigated in vivo and in vitro. The present study showed that resveratrol treatment alleviated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia. In vitro experiments showed that resveratrol notably inhibited proliferation of pulmonary arterial smooth muscle cells in an ER-independent manner. Data showed that resveratrol administration inhibited HIF-1 α expression in vivo and in vitro, suppressed inflammatory cells infiltration around the pulmonary arteries, and decreased ROS production induced by hypoxia in PAMSCs. The inflammatory cytokines' mRNA levels of tumor necrosis factor α, interleukin 6, and interleukin 1β were all suppressed by resveratrol treatment. The in vitro assays showed that resveratrol inhibited the expression of HIF-1 α via suppressing the MAPK/ERK1 and PI3K/AKT pathways. The antioxidant axis of Nuclear factor erythroid-2 related factor 2/ Thioredoxin 1 (Nrf-2/Trx-1) was up-regulated both in lung tissues and in cultured PASMCs. In general, the current study

  5. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats.

    PubMed

    Xu, Dunquan; Li, Yan; Zhang, Bo; Wang, Yanxia; Liu, Yi; Luo, Ying; Niu, Wen; Dong, Mingqing; Liu, Manling; Dong, Haiying; Zhao, Pengtao; Li, Zhichao

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development. Sprague-Dawley rats were challenged by hypoxia exposure for 28 days to mimic hypoxic pulmonary hypertension along with treating resveratrol (40 mg/kg/day). Hemodynamic and pulmonary pathomorphology data were then obtained, and the anti-proliferation effect of resveratrol was determined by in vitro assays. The anti-inflammation and anti-oxidative effects of resveratrol were investigated in vivo and in vitro. The present study showed that resveratrol treatment alleviated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia. In vitro experiments showed that resveratrol notably inhibited proliferation of pulmonary arterial smooth muscle cells in an ER-independent manner. Data showed that resveratrol administration inhibited HIF-1 α expression in vivo and in vitro, suppressed inflammatory cells infiltration around the pulmonary arteries, and decreased ROS production induced by hypoxia in PAMSCs. The inflammatory cytokines' mRNA levels of tumor necrosis factor α, interleukin 6, and interleukin 1β were all suppressed by resveratrol treatment. The in vitro assays showed that resveratrol inhibited the expression of HIF-1 α via suppressing the MAPK/ERK1 and PI3K/AKT pathways. The antioxidant axis of Nuclear factor erythroid-2 related factor 2/ Thioredoxin 1 (Nrf-2/Trx-1) was up-regulated both in lung tissues and in cultured PASMCs. In general, the current study

  6. High-Temperature Oxide Regrowth on Mechanically-Damaged Surfaces

    SciTech Connect

    Blau, Peter Julian; Lowe, Tracie M

    2008-01-01

    Here we report the effects of mechanical damage from a sharp stylus on the regrowth of oxide layers on a Ni-based superalloy known as Pyromet 80A . It was found that the oxide that reformed on the damaged portion of a pre-oxidized surface differed from that which formed on undamaged areas after the equal exposures to elevated temperature in air. These findings have broad implications for modeling the processes of material degradation in applications such as exhaust valves in internal combustion engines because they imply that static oxidation data for candidate materials may not adequately reflect their reaction to operating environments that involve both mechanical contact and oxidation.

  7. Methyl Jasmonate Alleviates Cadmium-Induced Photosynthetic Damages through Increased S-Assimilation and Glutathione Production in Mustard

    PubMed Central

    Per, Tasir S.; Khan, Nafees A.; Masood, Asim; Fatma, Mehar

    2016-01-01

    The effect of methyl jasmonate (MeJA) in mitigation of 50 μM cadmium (Cd) toxicity on structure and function of photosynthetic apparatus in presence or absence of 1.0 mM SO42– was investigated in mustard (Brassica juncea L. cv. Ro Agro 4001) at 30 days after sowing. Plants exhibited increased oxidative stress, impaired photosynthetic function when grown with Cd, but MeJA in presence of sulfur (S) more prominently ameliorated Cd effects through increased S-assimilation and production of reduced glutathione (GSH) and promoted photosynthetic functions. The transmission electron microscopy showed that MeJA protected chloroplast structure against Cd-toxicity. The use of GSH biosynthetic inhibitor, buthionine sulfoximine (BSO) substantiated the findings that ameliorating effect of MeJA was through GSH production. MeJA could not alleviate Cd effects when BSO was used due to unavailability of GSH even with the input of S. The study shows that MeJA regulates S-assimilation and GSH production for protection of structure and function of photosynthetic apparatus in mustard plants under Cd stress. PMID:28066485

  8. Rhizobial symbiosis alleviates polychlorinated biphenyls-induced systematic oxidative stress via brassinosteroids signaling in alfalfa.

    PubMed

    Wang, Xiaomi; Teng, Ying; Zhang, Ning; Christie, Peter; Li, Zhengao; Luo, Yongming; Wang, Jun

    2017-03-14

    The role of symbiotic rhizobia in the alleviation of polychlorinated biphenyl (PCB)-induced phytotoxicity in alfalfa and the brassinosteroid (BR) hormone signaling involved were investigated during phytoremediation. The association between alfalfa and Sinorhizobium meliloti was adopted as a remediation model. Phytotoxicity due to PCB 77 (3,3',4,4'-tetrachlorobiphenyl) exerted adverse impacts on plant performance (biomass accumulation and photosynthesis) and elicited cellular oxidative stress (overproduction of reactive oxygen species, lipid peroxidation, and cell necrosis) which was largely attenuated by pre-inoculation with S. meliloti strain NM. The protective role may have been achieved as a result of strengthening of basic antioxidant defense before stress as evidenced by the augmented activity and gene expression of antioxidative enzymes (peroxidase, glutathione reductase, superoxide dismutase, catalase, and ascorbate peroxidase) of both leaves and roots. In nodulated seedlings peroxidase showed additive increased activity following PCB exposure but the activities of the other four enzymes tended to remain stable after stress. Furthermore, application of strain NM and brassinolide both triggered the accumulation of endogenous BRs and the antioxidant network, while pre-treatment of seedlings with a biosynthetic inhibitor of BRs, brassinazole, abolished the rhizobia-induced activation of detoxification responses towards PCB. These observations indicate that association with S. meliloti NM enhanced the systemic antioxidant defenses of alfalfa to detoxify PCB, at least in part, via BR-dependent signaling pathways. These results contribute to our knowledge of the 'logistic role' played by rhizobia in assisting the phytoremediation of PCB-contaminated soils and suggest an optimum manipulation strategy for bioremediation.

  9. Hydrogen-rich water alleviates aluminum-induced inhibition of root elongation in alfalfa via decreasing nitric oxide production.

    PubMed

    Chen, Meng; Cui, Weiti; Zhu, Kaikai; Xie, Yanjie; Zhang, Chunhua; Shen, Wenbiao

    2014-02-28

    One of the earliest and distinct symptoms of aluminum (Al) toxicity is the inhibition of root elongation. Although hydrogen gas (H2) is recently described as an important bio-regulator in plants, whether and how H2 regulates Al-induced inhibition of root elongation is largely unknown. To address these gaps, hydrogen-rich water (HRW) was used to investigate a physiological role of H2 and its possible molecular mechanism. Individual or simultaneous (in particular) exposure of alfalfa seedlings to Al, or a fresh but not old nitric oxide (NO)-releasing compound sodium nitroprusside (SNP), not only increased NO production, but also led to a significant inhibition of root elongation. Above responses were differentially alleviated by pretreatment with 50% saturation of HRW. The addition of HRW also alleviated the appearance of Al toxicity symptoms, including the improvement of seedling growth and less accumulation of Al. Subsequent results revealed that the removal of NO by the NO scavenger, similar to HRW, could decrease NO production and alleviate Al- or SNP-induced inhibition of root growth. Thus, we proposed that HRW alleviated Al-induced inhibition of alfalfa root elongation by decreasing NO production. Such findings may be applicable to enhance crop yield and improve stress tolerance.

  10. Oxidative base damage in RNA detected by reverse transcriptase.

    PubMed Central

    Rhee, Y; Valentine, M R; Termini, J

    1995-01-01

    Oxidative base damage in DNA and metabolic defects in the recognition and removal of such damage play important roles in mutagenesis and human disease. The extent to which cellular RNA is a substrate for oxidative damage and the possible biological consequences of RNA base oxidation, however, remain largely unexplored. Since oxidatively modified RNA may contribute to the high mutability of retroviral genomic DNA, we have been interested in developing methods for the sequence specific detection of such damage. We show here that a primer extension assay using AMV reverse transcriptase (RT) can be used to reveal oxidatively damaged sites in RNA. This finding extends the currently known range of RNA modifications detectable with AMV reverse transcriptase. Analogous assays using DNA polymerases to detect base damage in DNA substrates appear to be restricted to lesions at thymine. Oxidative base damage in the absence of any detectable chain breaks was produced by dye photosensitization of RNA. Six out of 20 dyes examined were capable of producing RT detectable lesions. RT stops were seen predominantly at purines, although many pyrimidine sites were also detected. Dye specific photofootprints revealed by RT analysis suggests differential dye binding to the RNA substrate. Some of the photoreactive dyes described here may have potential utility in RNA structural analysis, particularly in the identification of stem-loop regions in complex RNAs. Images PMID:7545285

  11. Longterm melatonin administration alleviates paraquat mediated oxidative stress in Drosophila melanogaster.

    PubMed

    Medina-Leendertz, Shirley; Paz, Milagros; Mora, Marylú; Bonilla, Ernesto; Bravo, Yanauri; Arcaya, José Luis; Terán, Raikelin; Villalobos, Virginia

    2014-12-01

    We investigated the effect of melatonin (MEL) in the activities of cytosolic superoxide dismutase (SOD) and catalase as well as in the levels of H2O2 and mitochondrial malondialdehyde (MDA) in paraquat-intoxicated Drosophila melanogaster. Paraquat (40 mM) was administrated for 36 h. Three groups of flies intoxicated with paraquat were used: PQ (exposed during 36h to paraquat), PQ-MEL (exposed during 36h to paraquat and then treated with MEL [0.43 mM] for 12 days) and PQ-Control (maintained in standard corn meal for 12 days). Two additional groups without pre-intoxication with PQ were added: Control (maintained in standard corn meal) and MEL (treated with MEL for 12 days). Immediately after PQ intoxication the concentration of MDA (17.240 +/- 0.554 nmoles MDA/mg protein) and H2O2 (3.313 +/- 0.086 nmol hydrogen peroxide/mg protein) and the activities of SOD and catalase (419.667 + 0.731 and 0.216 +/- 0.009 Units/mg of protein, respectively) in the PQ group were significantly increased with respect to Control. After 12 days of intoxication with PQ, the PQ-Control flies showed in- creases in H2O2 (4.336 +/- 0.108) and MDA levels (8.620 +/- 0.156), and in the activities of SOD and catalase (692.570 +/- 0.433 and 0.327 +/- 0.003, respectively) as compared to PQ-MEL (p<0.001). Treatment with MEL extended the life span of the groups PQ-MEL and MEL when compared to their corresponding controls. Motor activity decreased significantly in PQ-Control and PQ-MEL flies, suggesting that the damage caused by PQ affected the nervous system of flies. Our findings showed that oxidative damage caused by paraquat was observed even after 12 days and that melatonin mitigates this damage.

  12. Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation.

    PubMed

    Zhang, Weixin; Yin, Lianhong; Tao, Xufeng; Xu, Lina; Zheng, Lingli; Han, Xu; Xu, Youwei; Wang, Changyuan; Peng, Jinyong

    2016-07-01

    In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future.

  13. Quercitrin protects skin from UVB-induced oxidative damage

    SciTech Connect

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

    2013-06-01

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

  14. 6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation

    PubMed Central

    Ghareib, Salah A; El-Bassossy, Hany M; Elberry, Ahmed A; Azhar, Ahmad; Watson, Malcolm L; Banjar, Zainy Mohammed

    2015-01-01

    The aim of the present study is to investigate the effect and potential mechanism of action of 6-gingerol on alterations of vascular reactivity in the isolated aorta from diabetic rats. Male Wistar rats were divided into two experimental groups, control and diabetics. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg kg−1), and the rats were left for 10 weeks to develop vascular complications. The effect of in vitro incubation with 6-gingerol (0.3–3 μM) on the vasoconstrictor response of the isolated diabetic aortae to phenylephrine and the vasodilator response to acetylcholine was examined. Effect of 6-gingerol was also examined on aortae incubated with methylglyoxal as an advanced glycation end product (AGE). To investigate the mechanism of action of 6-gingerol, the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride (100 μM), guanylate cyclase inhibitor methylene blue (5 μM), calcium-activated potassium channel blocker tetraethylammonium chloride (10 mM), and cyclooxygenase inhibitor indomethacin (5 μM) were added 30 minutes before assessing the direct vasorelaxant effect of 6-gingerol. Moreover, in vitro effects of 6-gingerol on NO release and the effect of 6-gingerol on AGE production were examined. Results showed that incubation of aortae with 6-gingerol (0.3–10 μM) alleviated the exaggerated vasoconstriction of diabetic aortae to phenylephrine in a concentration-dependent manner with no significant effect on the impaired relaxatory response to acetylcholine. Similar results were seen in the aortae exposed to methylglyoxal. In addition, 6-gingerol induced a direct vasodilation effect that was significantly inhibited by Nω-nitro-l-arginine methyl ester hydrochloride and methylene blue. Furthermore, 6-gingerol stimulated aortic NO generation but had no effect on AGE formation. In conclusion, 6-gingerol ameliorates enhanced vascular contraction in diabetic aortae, which may be partially

  15. Electrochemical study of DNA damaged by oxidation stress.

    PubMed

    Zitka, Ondrej; Krizkova, Sona; Skalickova, Sylvie; Kopel, Pavel; Babula, Petr; Adam, Vojtech; Kizek, Rene

    2013-02-01

    Many compounds can interact with DNA leading to changes of DNA structure as point mutation and bases excision, which could trigger some metabolic failures, which leads to the changes in DNA structure resulting in cancer. Oxidation of nucleic acid bases belongs to the one of the mostly occurred type of DNA damaging leading to the above mentioned phenomena. The investigation of processes of DNA oxidation damage is topical and electrochemical methods include a versatile and sensitive tool for these purposes. 8-hydroxydeoxyguanosine (8-OHdG) is the most widely accepted marker of DNA damage. Oxidative damage to DNA by free radicals and exposure to ionizing radiation generate several other products within the double helix besides mentioned oxidation products of nucleic acid bases. The basic electrochemical behaviour of nucleic acids bases on various types of carbon electrodes is reviewed. Further, we address our attention on description of oxidation mechanisms and on detection of the most important products of nucleic bases oxidation. The miniaturization of detector coupled with some microfluidic devices is suggested and discussed. The main aim of this review is to report the advantages and features of the electrochemical detection of guanine oxidation product as 8-OHdG and other similarly produced molecules as markers for DNA damage.

  16. Pre-anthesis high-temperature acclimation alleviates damage to the flag leaf caused by post-anthesis heat stress in wheat.

    PubMed

    Wang, Xiao; Cai, Jian; Jiang, Dong; Liu, Fulai; Dai, Tingbo; Cao, Weixing

    2011-04-15

    The objective of this study was to investigate the effect of pre-anthesis high-temperature acclimation on leaf physiology of winter wheat in response to post-anthesis heat stress. The results showed that both pre- and post-anthesis heat stresses significantly depressed flag leaf photosynthesis and enhanced cell membrane peroxidation, as exemplified by increased O₂⁻(·) production rate and reduction in activities of antioxiditave enzymes. However, under post-anthesis heat stress, plants with pre-anthesis high-temperature acclimation (HH) showed much higher photosynthetic rates than those without pre-anthesis high-temperature acclimation (CH). Leaves of HH plants exhibited a higher Chl a/b ratio and lower chlorophyll/carotenoid ratio and superoxide anion radical release rate compared with those of the CH plants. In addition, antioxidant enzyme activities in HH plants were significantly higher than in CH. Coincidently, expressions of photosythesis-responsive gene encoding Rubisco activase B (RcaB) and antioxidant enzyme-related genes encoding mitochondrial manganese superoxide dismutase (Mn-SOD), chloroplastic Cu/Zn superoxide dismutase (Cu/Zn-SOD), catalase (CAT) and cytosolic glutathione reductase (GR) were all up-regulated under HH, whereas a gene encoding a major chlorophyll a/b-binding protein (Cab) was up-regulated by post-anthesis heat stress at 10 DAA, but was down-regulated at 13 DAA. The changes in the expression levels of the HH plants were more pronounced than those for the CH. Collectively, the results indicated that pre-anthesis high-temperature acclimation could effectively alleviate the photosynthetic and oxidative damage caused by post-anthesis heat stress in wheat flag leaves, which was partially attributable to modifications in the expression of the photosythesis-responsive and antioxidant enzymes-related genes.

  17. Oxidative damage in multiple sclerosis lesions.

    PubMed

    Haider, Lukas; Fischer, Marie T; Frischer, Josa M; Bauer, Jan; Höftberger, Romana; Botond, Gergö; Esterbauer, Harald; Binder, Christoph J; Witztum, Joseph L; Lassmann, Hans

    2011-07-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are currently poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Since mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, we analysed by immunocytochemistry the presence and cellular location of oxidized lipids and oxidized DNA in lesions and in normal-appearing white matter of 30 patients with multiple sclerosis and 24 control patients without neurological disease or brain lesions. As reported before in biochemical studies, oxidized lipids and DNA were highly enriched in active multiple sclerosis plaques, predominantly in areas that are defined as initial or 'prephagocytic' lesions. Oxidized DNA was mainly seen in oligodendrocyte nuclei, which in part showed signs of apoptosis. In addition, a small number of reactive astrocytes revealed nuclear expression of 8-hydroxy-d-guanosine. Similarly, lipid peroxidation-derived structures (malondialdehyde and oxidized phospholipid epitopes) were seen in the cytoplasm of oligodendrocytes and some astrocytes. In addition, oxidized phospholipids were massively accumulated in a fraction of axonal spheroids with disturbed fast axonal transport as well as in neurons within grey matter lesions. Neurons stained for oxidized phospholipids frequently revealed signs of degeneration with fragmentation of their dendritic processes. The extent of lipid and DNA oxidation correlated significantly with inflammation, determined by the number of CD3 positive T cells and human leucocyte antigen-D expressing macrophages and microglia in the lesions. Our data suggest profound oxidative injury of oligodendrocytes and neurons to be associated with active demyelination and axonal or neuronal injury in multiple sclerosis.

  18. OXIDATIVE DNA DAMAGE IN DIESEL BUS MECHANICS

    EPA Science Inventory

    Rationale:

    Diesel exposure has been associated with adverse health effects, including susceptibility to asthma, allergy and cancer. Previous epidemiological studies demonstrated increased cancer incidence among workers exposed to diesel. This is likely due to oxid...

  19. Strong, damage tolerant oxide-fiber/oxide matrix composites

    NASA Astrophysics Data System (ADS)

    Bao, Yahua

    cationic polyelectrolytes to have a positive surface charge and then dipped into diluted, negatively-charged AlPO4 colloidal suspension (0.05M) at pH 7.5. Amorphous AlPO4 (crystallizes to tridymite- and cristobalite-forms at 1080°C) nano particles were coated on fibers layer-by-layer using an electrostatic attraction protocol. A uniform and smooth coating was formed which allowed fiber pullout from the matrix of a Nextel 720/alumina mini-composite hot-pressed at 1250°C/20MPa. Reaction-bonded mullite (RBM), with low formation temperature and sintering shrinkage was synthesized by incorporation of mixed-rare-earth-oxide (MREO) and mullite seeds. Pure mullite formed with 7.5wt% MREO at 1300°C. Introduction of 5wt% mullite seeds gave RBM with less than 3% shrinkage and 20% porosity. AlPO4-coated Nextel 720/RBM composites were successful fabricated by EPID and pressureless sintering at 1300°C. Significant fiber pullout occurred and the 4-point bend strength was around 170MPa (with 25-30vol% fibers) at room temperature and 1100°C and a Work-of-Fracture 7KJ/m2. At 1200°C, the composite failed in shear due to the MREO-based glassy phase in the matrix. AlPO4-coated Nextel 720 fiber/aluminosilicate (no MREO) showed damage tolerance at 1200°C with a bend strength 170MPa.

  20. Photoexcited riboflavin induces oxidative damage to human serum albumin

    NASA Astrophysics Data System (ADS)

    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.

  1. Superoxide and the production of oxidative DNA damage.

    PubMed Central

    Keyer, K; Gort, A S; Imlay, J A

    1995-01-01

    The conventional model of oxidative DNA damage posits a role for superoxide (O2-) as a reductant for iron, which subsequently generates a hydroxyl radical by transferring the electron to H2O2. The hydroxyl radical then attacks DNA. Indeed, mutants of Escherichia coli that lack superoxide dismutase (SOD) were 10-fold more vulnerable to DNA oxidation by H2O2 than were wild-type cells. Even the pace of DNA damage by endogenous oxidants was great enough that the SOD mutants could not tolerate air if enzymes that repair oxidative DNA lesions were inactive. However, DNA oxidation proceeds in SOD-proficient cells without the involvement of O2-, as evidenced by the failure of SOD overproduction or anaerobiosis to suppress damage by H2O2. Furthermore, the mechanism by which excess O2- causes damage was called into question when the hypersensitivity of SOD mutants to DNA damage persisted for at least 20 min after O2- had been dispelled through the imposition of anaerobiosis. That behavior contradicted the standard model, which requires that O2- be present to rereduce cellular iron during the period of exposure to H2O2. Evidently, DNA oxidation is driven by a reductant other than O2-, which leaves the mechanism of damage promotion by O2- unsettled. One possibility is that, through its well-established ability to leach iron from iron-sulfur clusters, O2- increases the amount of free iron that is available to catalyze hydroxyl radical production. Experiments with iron transport mutants confirmed that increases in free-iron concentration have the effect of accelerating DNA oxidation. Thus, O2- may be genotoxic only in doses that exceed those found in SOD-proficient cells, and in those limited circumstances it may promote DNA damage by increasing the amount of DNA-bound iron. PMID:7592468

  2. Oxidative DNA Damage in Blood of CVD Patients Taking Detralex

    PubMed Central

    Krzyściak, Wirginia; Cierniak, Agnieszka; Kózka, Mariusz; Kozieł, Joanna

    2011-01-01

    The main goal of the work reported here was to determine the degree of oxidative/alkali-labile DNA damages in peripheral blood as well as in the blood stasis from varicose vein of (chronic venous disorder) CVD patients. Moreover, determination of the impact of Detralex usage on the level of (oxidative) DNA damages in CVD patients was evaluated as well. The degree of oxidative DNA damages was studied in a group consisted of thirty patients with diagnosed chronic venous insufficiency (CVI) in the 2nd and 3rd degree, according to clinical state, etiology, anatomy and pathophysiology (CEAP), and qualified to surgical procedure. The control group consisted of normal volunteers (blood donors) qualified during standard examinations at Regional Centers of Blood Donation and Blood Therapy. The comet assay was used for determination of DNA damages. Analyses of the obtained results showed increase in the level of oxidative/alkali-labile DNA damages in lymphocytes originating from antebrachial blood of CVD patients as compared to the control group (Control) (p < 0.002; ANOVA). In addition, it was demonstrated that the usage of Detralex® resulted in decrease of the level of oxidative/alkali-labile DNA damages in CVD patients as compared to patients without Detralex® treatment (p < 0.001; ANOVA). Based on findings from the study, it may be hypothesized about occurrence of significant oxidative DNA damages as the consequence of strong oxidative stress in CVD. In addition, antioxidative effectiveness of Detralexu® was observed at the recommended dose, one tablet twice daily. PMID:21912579

  3. Oxidative DNA damage in osteoarthritic porcine articular cartilage

    PubMed Central

    Chen, Antonia F.; Davies, Catrin M.; De Lin, Ming; Fermor, Beverley

    2008-01-01

    Purpose Osteoarthritis (OA) is associated with increased levels of reactive oxygen species. This study investigated if increased oxidative DNA damage accumulates in OA articular cartilage compared with non-OA articular cartilage from pigs with spontaneous OA. Additionally, the ability of nitric oxide (NO) or peroxynitrite (ONOO-) induced DNA damage in non-OA chondrocytes to undergo endogenous repair was investigated. Methods Porcine femoral condyles were graded for the stage of OA, macroscopically by the Collins Scale, and histologically by the modified Mankin Grade. Levels of DNA damage were determined in non-OA and OA cartilage, using the comet assay. For calibration, DNA damage was measured by exposing non-OA chondrocytes to 0-12 Gray of x-ray irradiation. Non-OA articular chondrocytes were treated with 0-500 μM of NO donors (NOC-18 or SIN-1), and DNA damage assessed after treatment and 5 days recovery. Results A significant increase (p<0.01) in oxidative DNA damage occurred in OA chondrocytes in joints with Mankin Grades 3 or greater, compared to non-OA chondrocytes. The percentage of nuclei containing DNA damage increased significantly (p<0.001) from early to late grades of OA. An increase of approximately 0.65-1.7 breaks/1000kB of DNA occurred in OA, compared to non-OA nuclei. NOC-18 or SIN-1 caused significant DNA damage (p<0.001) in non-OA chondrocytes that did not undergo full endogenous repair after 5 days (p<0.05). Conclusion Our data suggest significant levels of oxidative DNA damage occur in OA chondrocytes that accumulates with OA progression. Additionally, DNA damage induced by NO and ONOO- in non-OA chondrocytes does not undergo full endogenous repair. PMID:18720406

  4. Gibberellic acid alleviates cadmium toxicity by reducing nitric oxide accumulation and expression of IRT1 in Arabidopsis thaliana.

    PubMed

    Zhu, Xiao Fang; Jiang, Tao; Wang, Zhi Wei; Lei, Gui Jie; Shi, Yuan Zhi; Li, Gui Xin; Zheng, Shao Jian

    2012-11-15

    Gibberellic acid (GA) is involved in not only plant growth and development but also plant responses to abiotic stresses. Here it was found that treating the plants with GA concentrations from 0.1 to 5 μM for 24 h had no obvious effect on root elongation in the absence of cadmium (Cd), whereas in the presence of Cd2+, GA at 5 μM improved root growth, reduced Cd content and lipid peroxidation in the roots, indicating that GA can partially alleviate Cd toxicity. Cd2+ increased nitric oxide (NO) accumulation in the roots, but GA remarkably reduced it, and suppressed the up-regulation of the expression of IRT1. In contrary, the beneficial effect of GA on alleviating Cd toxicity was not observed in an IRT1 knock-out mutant irt1, suggesting the involvement of IRT1 in Cd2+ absorption. Furthermore, the GA-induced reduction of NO and Cd content can also be partially reversed by the application of a NO donor (S-nitrosoglutathione [GSNO]). Taken all these together, the results showed that GA-alleviated Cd toxicity is mediated through the reduction of the Cd-dependent NO accumulation and expression of Cd2+ uptake related gene-IRT1 in Arabidopsis.

  5. Oxidative DNA damage and repair in teratogenesis and neurodevelopmental deficits.

    PubMed

    Wells, Peter G; McCallum, Gordon P; Lam, Kyla C H; Henderson, Jeffrey T; Ondovcik, Stephanie L

    2010-06-01

    Several teratogenic agents, including ionizing radiation and xenobiotics such as phenytoin, benzo[a]pyrene, thalidomide, and methamphetamine, can initiate the formation of reactive oxygen species (ROS) that oxidatively damage cellular macromolecules including DNA. Oxidative DNA damage, and particularly the most prevalent 8-oxoguanine lesion, may adversely affect development, likely via alterations in gene transcription rather than via a mutational mechanism. Contributions from oxidative DNA damage do not exclude roles for alternative mechanisms of initiation like receptor-mediated processes or the formation of covalent xenobiotic-macromolecular adducts, damage to other macromolecular targets like proteins and lipids, and other effects of ROS like altered signal transduction. Even in the absence of teratogen exposure, endogenous developmental oxidative stress can have embryopathic consequences in the absence of key pathways for detoxifying ROS or repairing DNA damage. Critical proteins in pathways for DNA damage detection/repair signaling, like p53 and ataxia telangiectasia mutated, and DNA repair itself, like oxoguanine glycosylase 1 and Cockayne syndrome B, can often, but not always, protect the embryo from ROS-initiating teratogens. Protection may be variably dependent upon such factors as the nature of the teratogen and its concentration within the embryo, the stage of development, the species, strain, gender, target tissue and cell type, among other factors.

  6. Acrylonitrile-Induced Oxidative Stress and Oxidative DNA Damage in Male Sprague-Dawley Rats

    PubMed Central

    Kamendulis, Lisa M.; Klaunig, James E.

    2009-01-01

    Studies have demonstrated that the induction of oxidative stress may be involved in brain tumor induction in rats by acrylonitrile. The present study examined whether acrylonitrile induces oxidative stress and DNA damage in rats and whether blood can serve as a valid surrogate for the biomonitoring of oxidative stress induced by acrylonitrile in the exposed population. Male Sprague-Dawley rats were treated with 0, 3, 30, 100, and 200 ppm acrylonitrile in drinking water for 28 days. One group of rats were also coadministered N-acetyl cysteine (NAC) (0.3% in diet) with acrylonitrile (200 ppm in drinking water) to examine whether antioxidant supplementation was protective against acrylonitrile-induced oxidative stress. Direct DNA strand breakage in white blood cells (WBC) and brain was measured using the alkaline comet assay. Oxidative DNA damage in WBC and brain was evaluated using formamidopyrimidine DNA glycosylase (fpg)-modified comet assay and with high-performance liquid chromatography-electrochemical detection. No significant increase in direct DNA strand breaks was observed in brain and WBC from acrylonitrile-treated rats. However, oxidative DNA damage (fpg comet and 8′hydroxyl-2-deoxyguanosine) in brain and WBC was increased in a dose-dependent manner. In addition, plasma levels of reactive oxygen species (ROS) increased in rats administered acrylonitrile. Dietary supplementation with NAC prevented acrylonitrile-induced oxidative DNA damage in brain and WBC. A slight, but significant, decrease in the GSH:GSSG ratio was seen in brain at acrylonitrile doses > 30 ppm. These results provide additional support that the mode of action for acrylonitrile-induced astrocytomas involves the induction of oxidative stress and damage. Significant associations were seen between oxidative DNA damage in WBC and brain, ROS formation in plasma, and the reported tumor incidences. Since oxidative DNA damage in brain correlated with oxidative damage in WBC, these results suggest

  7. Oxidative Damage in Parkinson’s Disease

    DTIC Science & Technology

    2003-01-01

    supranuclear palsy brains. There were no significant alterations in 8-hydroxy-2- deoxyguanosine in the plasma of PD patients. We found that...patients and a number of specific genes linked to oxidative stress were reduced in expression. There was increased lipid peroxidation in progressive

  8. Potential role of punicalagin against oxidative stress induced testicular damage

    PubMed Central

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

  9. Protective effect of Pterostilbene against free radical mediated oxidative damage

    PubMed Central

    2013-01-01

    Background Pterostilbene, a methoxylated analog of Resveratrol, is gradually gaining more importance as a therapeutic drug owing to its higher lipophilicity, bioavailability and biological activity than Resveratrol. This study was undertaken to characterize its ability to scavenge free radicals such as superoxide, hydroxyl and hydrogen peroxide and to protect bio-molecules within a cell against oxidative insult. Methods Anti-oxidant activity of Pterostilbene was evaluated extensively by employing several in vitro radical scavenging/inhibiting assays and pulse radiolysis study. In addition, its ability to protect rat liver mitochondria against tertiary-butyl hydroperoxide (TBHP) and hydroxyl radical generated oxidative damage was determined by measuring the damage markers such as protein carbonyls, protein sulphydryls, lipid hydroperoxides, lipid peroxides and 8-hydroxy-2'-deoxyguanosine. Pterostilbene was also evaluated for its ability to inhibit •OH radical induced single strand breaks in pBR322 DNA. Result Pterostilbene exhibited strong anti-oxidant activity against various free radicals such as DPPH, ABTS, hydroxyl, superoxide and hydrogen peroxide in a concentration dependent manner. Pterostilbene conferred protection to proteins, lipids and DNA in isolated mitochondrial fractions against TBHP and hydroxyl radical induced oxidative damage. It also protected pBR322 DNA against oxidative assault. Conclusions Thus, present study provides an evidence for the strong anti-oxidant property of Pterostilbene, methoxylated analog of Resveratrol, thereby potentiating its role as an anti-oxidant. PMID:24070177

  10. Potential role of punicalagin against oxidative stress induced testicular damage.

    PubMed

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  11. Dexamethasone Pretreatment Alleviates Isoniazid/Lipopolysaccharide Hepatotoxicity: Inhibition of Inflammatory and Oxidative Stress

    PubMed Central

    Hassan, Hozeifa M.; Guo, Hongli; Yousef, Bashir A.; Ping-Ping, Ding; Zhang, Luyong; Jiang, Zhenzhou

    2017-01-01

    Isoniazid (INH) remains a cornerstone key constitute of the current tuberculosis management strategy, but its hepatotoxic potentiality remains a significant clinical problem. Our previous findings succeed to establish a rat model of INH hepatotoxicity employing the inflammatory stress theory in which non-injurious doses of inflammatory-mediating agent bacterial lipopolysaccharides (LPS) augmented the toxicity of INH that assist to uncover the mechanisms behind INH hepatotoxicity. Following LPS exposure, several inflammatory cells are activated and it is likely that the consequences of this activation rather than direct hepatocellular effects of LPS underlie the ability of LPS to augment toxic responses. In this study, we investigated the potential protective role of the anti-inflammatory agent dexamethasone (DEX), a potent synthetic glucocorticoid, in INH/LPS hepatotoxic rat model. DEX pre-treatment successfully eliminates the components of the inflammatory stress as shown through analysis of blood biochemistry and liver histopathology. DEX potentiated hepatic anti-oxidant mechanisms while serum and hepatic lipid profiles were reduced. However, DEX administration was not able to revoke the principal effects of cytochrome P450 2E1 (CYP2E1) in INH/LPS-induced liver damage. In conclusion, this study illustrated the DEX-preventive capabilities on INH/LPS-induced hepatotoxicity model through DEX-induced potent anti-inflammatory activity whereas the partial toxicity seen in the model could be attributed to the expression of hepatic CYP2E1. These findings potentiate the clinical applications of DEX co-administration with INH therapy in order to reduce the potential incidences of hepatotoxicity. PMID:28360859

  12. Inhibition of Glucose-6-Phosphate Dehydrogenase Could Enhance 1,4-Benzoquinone-Induced Oxidative Damage in K562 Cells

    PubMed Central

    Cao, Meng; Yang, Wenwen; Sun, Fengmei; Xu, Cheng

    2016-01-01

    Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4-benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure. PMID:27656260

  13. Oxidative damage, skin aging, antioxidants and a novel antioxidant rating system.

    PubMed

    Palmer, Debbie M; Kitchin, Jennifer Silverman

    2010-01-01

    It is believed that oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to neutralize the reactive intermediates. Oxidative damage occurs because of both intrinsic and extrinsic mechanisms. Together, intrinsic and extrinsic damage are the primary causes of skin aging. The skin uses a series of intrinsic antioxidants to protect itself from free radical damage. Naturally occurring extrinsic antioxidants have also been widely shown to offset and alleviate these changes. Unlike sunscreens, which have an SPF rating system to guide consumers in their purchases, there is no widely accepted method to choose antioxidant anti-aging products. ORAC (Oxygen Radical Absorbance Capacity) and ABEL-RAC (Analysis By Emitted Light-Relative Antioxidant Capacity), are both accepted worldwide as a standard measure of the antioxidant capacity of foods, and are rating systems that could be applied to all antioxidant skincare products. The standardization of antioxidant creams could revolutionize the cosmeceutical market and give physicians and consumers the ability to compare and choose effectively.

  14. Maternal diabetes triggers DNA damage and DNA damage response in neurulation stage embryos through oxidative stress

    PubMed Central

    Dong, Daoyin; Yu, Jingwen; Wu, Yanqing; Fu, Noah; Villela, Natalia Arias; Yang, Peixin

    2015-01-01

    DNA damage and DNA damage response (DDR) in neurulation stage embryos under maternal diabetes conditions are not well understood. The purpose of this study was to investigate whether maternal diabetes and high glucose in vitro induce DNA damage and DDR in the developing embryo through oxidative stress. In vivo experiments were conducted by mating superoxide dismutase 1 (SOD1) transgenic male mice with wild-type (WT) female mice with or without diabetes. Embryonic day 8.75 (E8.75) embryos were tested for the DNA damage markers, phosphorylated histone H2A.X (p-H2A.X) and DDR signaling intermediates, including phosphorylated checkpoint 1 (p-Chk1), phosphorylated checkpoint 2 (p-Chk2), and p53. Levels of the same DNA damage markers and DDR signaling intermediates were also determined in the mouse C17.2 neural stem cell line. Maternal diabetes and high glucose in vitro significantly increased the levels of p-H2A.X. Levels of p-Chk1, p-Chk2, and p53, were elevated under both maternal diabetic and high glucose conditions. SOD1 overexpression blocked maternal diabetes-induced DNA damage and DDR in vivo. Tempol, a SOD1 mimetic, diminished high glucose-induced DNA damage and DDR in vitro. In conclusion, maternal diabetes and high glucose in vitro induce DNA damage and activates DDR through oxidative stress, which may contribute to the pathogenesis of diabetes-associated embryopathy. PMID:26427872

  15. Oxidative DNA damage in mouse sperm chromosomes: Size matters.

    PubMed

    Kocer, Ayhan; Henry-Berger, Joelle; Noblanc, Anais; Champroux, Alexandre; Pogorelcnik, Romain; Guiton, Rachel; Janny, Laurent; Pons-Rejraji, Hanae; Saez, Fabrice; Johnson, Graham D; Krawetz, Stephen A; Alvarez, Juan G; Aitken, R John; Drevet, Joël R

    2015-12-01

    Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models that display high levels of sperm oxidative DNA damage, a common alteration encountered both in in vivo and in vitro reproduction. Immunoprecipitation of oxidized sperm DNA coupled to deep sequencing showed that mouse chromosomes may be largely affected by oxidative alterations. We show that the vulnerability of chromosomes to oxidative attack inversely correlated with their size and was not linked to their GC richness. It was neither correlated with the chromosome content in persisting nucleosomes nor associated with methylated sequences. A strong correlation was found between oxidized sequences and sequences rich in short interspersed repeat elements (SINEs). Chromosome position in the sperm nucleus as revealed by fluorescent in situ hybridization appears to be a confounder. These data map for the first time fragile mouse sperm chromosomal regions when facing oxidative damage that may challenge the repair mechanisms of the oocyte post-fertilization.

  16. Cysteamine alleviates early brain injury via reducing oxidative stress and apoptosis in a rat experimental subarachnoid hemorrhage model.

    PubMed

    Zhang, Zong-Yong; Yang, Ming-Feng; Wang, Tao; Li, Da-Wei; Liu, Yun-Lin; Zhang, Jin-Hui; Sun, Bao-Liang

    2015-05-01

    Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The aim of this study was to assess whether cysteamine prevents post-SAH oxidative stress injury via its antioxidative and anti-apoptotic effects. It was observed that intraperitoneal administration of cysteamine (20 mg/kg/day) could significantly alleviate EBI (including neurobehavioral deficits, brain edema, blood-brain barrier permeability, and cortical neuron apoptosis) after SAH in rats. Meanwhile, cysteamine treatment reduced post-SAH elevated the reactive oxygen species level, the concentration of malondialdehyde, 3-nitrotyrosine, and 8-hydroxydeoxyguanosine and increased the glutathione peroxidase enzymatic activity, the concentration of glutathione and brain-derived neurotrophic factor in brain cortex at 48 h after SAH. These results indicated that administration of cysteamine may ameliorate EBI and provide neuroprotection after SAH in rat models.

  17. Quercitrin protects skin from UVB-induced oxidative damage.

    PubMed

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

    2013-06-01

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

  18. Inducible repair of oxidative DNA damage in Escherichia coli.

    PubMed

    Demple, B; Halbrook, J

    Hydrogen peroxide is lethal to many cell types, including the bacterium Escherichia coli. Peroxides yield transient radical species that can damage DNA and cause mutations. Such partially reduced oxygen species are occasionally released during cellular respiration and are generated by lethal and mutagenic ionizing radiation. Because cells live in an environment where the threat of oxidative DNA damage is continual, cellular mechanisms may have evolved to avoid and repair this damage. Enzymes are known which evidently perform these functions. We report here that resistance to hydrogen peroxide toxicity can be induced in E. coli, that this novel induction is specific and occurs, in part, at the level of DNA repair.

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

    PubMed

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

    2015-09-30

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

  20. Lead and cadmium-induced oxidative stress impacting mycelial growth of Oudemansiella radicata in liquid medium alleviated by microbial siderophores.

    PubMed

    Cao, Yan-Ru; Zhang, Xi-Yu; Deng, Jia-Yu; Zhao, Qi-Qi; Xu, Heng

    2012-04-01

    In this study, the effects of siderophores produced by six bacteria on mycelium growth, Cd and Pb accumulation, lipid peroxidation, protein content and antioxidant enzyme in Oudemansiella radicata were investigated in Cd and Pb-containing liquid medium. The results showed that inoculation with siderophore-containing filtrates (SCF) partly enhanced the growth of O. radicata after 15 days, with 0.8-32.4% biomass increase for Cd and 0.7-20.8% for Pb compared to control(s), which lacked siderophore. The maximum enhancement for accumulation were found to be confined to Bacillus sp. FFQ2(s) (26.5%) for Cd and Pseudomonas sp. CY63(s) (158.9%) for Pb. A significant decrease in MDA content indicated that lipid peroxidation in O. radicata was alleviated by siderophores. Besides, antioxidant enzyme SOD and POD activities also displayed obviously decrease in SCF-treated mycelium compared to control(s) treatment, while CAT activity did not present significant change. Protein level in O. radicata treated by SCF increased from 0.3 to 138.0% for Cd and from 10.9 to 107.1% for Pb compared to control(s). Therefore, the present work suggests that microbial siderophores can reduce the toxicity of metals to mycelium and then alleviate heavy metals-inducing oxidative stress in O. radicata.

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

    PubMed

    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.

  2. Anti- and pro-oxidant effects of (+)-catechin on hemoglobin-induced protein oxidative damage.

    PubMed

    Lu, Naihao; Chen, Puqing; Yang, Qin; Peng, Yi-Yuan

    2011-06-01

    Evidence to support the role of heme proteins as major inducers of oxidative damage is increasingly present. Flavonoids have been widely used to ameliorate oxidative damage in vivo and in vitro, where the mechanism of this therapeutic action was usually dependent on their anti-oxidant effects. In this study, we investigated the influence of (+)-catechin, a polyphenol identified in tea, cocoa, and red wine, on hemoglobin-induced protein oxidative damage. It was found that (+)-catechin had the capacities to act as a free radical scavenger and reducing agent to remove cytotoxic ferryl hemoglobin, demonstrating apparent anti-oxidant activities. However, the presence of (+)-catechin surprisingly promoted hemoglobin-induced protein oxidation, which was probably due to the ability of this anti-oxidant to rapidly trigger the oxidative degradation of normal hemoglobin. In addition, hemoglobin-H2O2-induced protein carbonyl formation was significantly enhanced by (+)-catechin at lower concentrations, while it was efficiently inhibited when higher concentrations were used. These novel results showed that the dietary intake and therapeutic use of catechins might possess pro-oxidant activity through aggravating hemoglobin-related oxidative damage. The dual effects on hemoglobin redox reactions may provide new insights into the physiological implications of tea extract and wine (catechins) with cellular heme proteins.

  3. Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

    PubMed Central

    Rodríguez-Lara, Simón Quetzalcoatl; Ramírez-Lizardo, Ernesto Javier; Totsuka-Sutto, Sylvia Elena; Castillo-Romero, Araceli; García-Cobián, Teresa Arcelia

    2016-01-01

    Ischemia/reperfusion (I/R) lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states. PMID:28116037

  4. Alleviation of salt-induced oxidative damage by 5-aminolevulinic acid in wheat seedlings

    NASA Astrophysics Data System (ADS)

    Genişel, Mucip; Erdal, Serkan

    2016-04-01

    The aim of this study was to elucidate how 5-aminolevulinic acid (ALA), the precursor of chlorophyll compounds, affects the defence mechanisms of wheat seedlings induced by salt stress. To determine the possible stimulative effects of ALA against salinity, 11-day old wheat seedlings were sprayed with ALA at two different concentrations (10 and 20 mg.l-1) and then stressed by exposure to salt (150 mM NaCl). The salt stress led to significant changes in the antioxidant activity. While guaiacol peroxidase activity decreased, the activities of superoxide dismutase, catalase, and ascorbate peroxidase markedly increased under salt stress. Compared to the salt stress alone, the application of ALA beforehand further increased the activity of these enzymes. This study is the first time the effects of ALA have been monitored with regard to protein content and the isoenzyme profiles of the antioxidant enzymes. Although the salt stress reduced both the soluble protein content and protein band intensities, pre-treating with ALA significantly mitigated these stress-induced reductions. The data for the isoenzyme profiles of the antioxidant enzymes paralleled that of the ALA-induced increases in antioxidant activity. As a consequence of the high antioxidant activity in the seedlings pre-treated with ALA, the stress-induced elevations in the reactive oxygen species, superoxide anion, and hydrogen peroxide contents and lipid peroxidation levels were markedly diminished. Taken together, this data demonstrated that pre-treating with ALA confers resistance to salt stress by modulating the protein synthesis and antioxidant activity in wheat seedlings.

  5. Curcumin improves vascular function and alleviates oxidative stress in non-lethal lipopolysaccharide-induced endotoxaemia in mice.

    PubMed

    Sompamit, Kwanjit; Kukongviriyapan, Upa; Nakmareong, Saowanee; Pannangpetch, Patchareewan; Kukongviriyapan, Veerapol

    2009-08-15

    Oxidative stress is implicated in various pathological conditions, including septic shock, and other diseases associated with local or systemic inflammation. Curcumin, a major component from turmeric (Curcuma longa), possesses diverse anti-inflammatory, anti-tumour and antioxidant properties. The aim of this study was to investigate the effect of curcumin on modulation of vascular dysfunction and oxidative stress induced by lipopolysaccharide (LPS) in mice. Male ICR mice were treated with curcumin (50 or 100 mg/kg), administered intragastrically, either before or after intraperitoneal injection of LPS (10 mg/kg). Fifteen hours after LPS administration, arterial blood pressure was measured and vascular response to vasoactive agents were assessed. Aortic tissues and blood samples were taken for assays of antioxidant and oxidative stress markers. LPS caused marked hypotension, tachycardia and vascular hyporeactivity. The mean arterial pressures in responses to phenylephrine, acetylcholine, and sodium nitroprusside of LPS-treated mice were significantly decreased when compared with the untreated controls. Curcumin modulated heart rate and restored arterial blood pressure in a dose-dependent manner in both protectively- and therapeutically-treated regimens. Furthermore, the vascular responsiveness of LPS-treated mice was improved by curcumin. Interestingly, the improvements of haemodynamics and vascular response during endotoxaemia were related to alleviation of oxidative stress by reducing aortic-derived superoxide production, suppression of lipid peroxidation and protein oxidation, and decrease in urinary nitric oxide metabolites with preservation of the ratio of glutathione/glutathione disulfide. This study provides the first evidence for the potential role of curcumin in prevention and treatment of vascular dysfunction in mice with endotoxaemia elicited by LPS.

  6. Strategy to Suppress Oxidative Damage-Induced Neurotoxicity in PC12 Cells by Curcumin: the Role of ROS-Mediated DNA Damage and the MAPK and AKT Pathways.

    PubMed

    Fu, Xiao-yan; Yang, Ming-feng; Cao, Ming-zhi; Li, Da-wei; Yang, Xiao-yi; Sun, Jing-yi; Zhang, Zong-yong; Mao, Lei-lei; Zhang, Shuai; Wang, Feng-ze; Zhang, Feng; Fan, Cun-dong; Sun, Bao-liang

    2016-01-01

    Oxidative damage plays a key role in causation and progression of neurodegenerative diseases. Inhibition of oxidative stress represents one of the most effective ways in treating human neurologic diseases. Herein, we evaluated the protective effect of curcumin on PC12 cells against H2O2-induced neurotoxicity and investigated its underlying mechanism. The results indicated that curcumin pre-treatment significantly suppressed H2O2-induced cytotoxicity, inhibited the loss of mitochondrial membrane potential (Δψm) through regulation of Bcl-2 family expression, and ultimately reversed H2O2-induced apoptotic cell death in PC12 cells. Attenuation of caspase activation, poly(ADP-ribose) polymerase (PARP) cleavage, DNA damage, and accumulation of reactive oxygen species (ROS) all confirmed its protective effects. Moreover, curcumin markedly alleviated the dysregulation of the MAPK and AKT pathways induced by H2O2. Taken together, our findings suggest that the strategy of using curcumin could be a highly effective way in combating oxidative damage-mediated human neurodegenerative diseases.

  7. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    PubMed

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent.

  8. Maternal diabetes triggers DNA damage and DNA damage response in neurulation stage embryos through oxidative stress.

    PubMed

    Dong, Daoyin; Yu, Jingwen; Wu, Yanqing; Fu, Noah; Villela, Natalia Arias; Yang, Peixin

    2015-11-13

    DNA damage and DNA damage response (DDR) in neurulation stage embryos under maternal diabetes conditions are not well understood. The purpose of this study was to investigate whether maternal diabetes and high glucose in vitro induce DNA damage and DDR in the developing embryo through oxidative stress. In vivo experiments were conducted by mating superoxide dismutase 1 (SOD1) transgenic male mice with wild-type (WT) female mice with or without diabetes. Embryonic day 8.75 (E8.75) embryos were tested for the DNA damage markers, phosphorylated histone H2A.X (p-H2A.X) and DDR signaling intermediates, including phosphorylated checkpoint 1 (p-Chk1), phosphorylated checkpoint 2 (p-Chk2), and p53. Levels of the same DNA damage markers and DDR signaling intermediates were also determined in the mouse C17.2 neural stem cell line. Maternal diabetes and high glucose in vitro significantly increased the levels of p-H2A.X. Levels of p-Chk1, p-Chk2, and p53, were elevated under both maternal diabetic and high glucose conditions. SOD1 overexpression blocked maternal diabetes-induced DNA damage and DDR in vivo. Tempol, a SOD1 mimetic, diminished high glucose-induced DNA damage and DDR in vitro. In conclusion, maternal diabetes and high glucose in vitro induce DNA damage and activates DDR through oxidative stress, which may contribute to the pathogenesis of diabetes-associated embryopathy.

  9. Dietary rosemary oil alleviates heat stress-induced structural and functional damage through lipid peroxidation in the testes of growing Japanese quail.

    PubMed

    Türk, Gaffari; Çeribaşı, Ali O; Şimşek, Ülkü G; Çeribaşı, Songül; Güvenç, Mehmet; Özer Kaya, Şeyma; Çiftçi, Mehmet; Sönmez, Mustafa; Yüce, Abdurrauf; Bayrakdar, Ali; Yaman, Mine; Tonbak, Fadime

    2016-01-01

    Supplementation of natural antioxidants to diets of male poultry has been reported to be effective in reducing or completely eliminating heat stress (HS)-induced reproductive failures. In this study, the aim is to investigate whether rosemary oil (RO) has a protective effect on HS-induced damage in spermatozoa production, testicular histologic structures, apoptosis, and androgenic receptor (AR) through lipid peroxidation mechanisms in growing Japanese quail. Male chicks (n=90) at 15-days of age were assigned to two groups. The first group (n=45) was kept in a thermo-neutral (TN) room at 22°C for 24h/d. The second group (n=45) was kept in a room with a greater ambient temperature of 34°C for 8h/d (from 9:00 AM to 5:00 PM) and 22°C for 16h/d. Animals in each of these two groups were randomly assigned to three subgroups (RO groups: 0, 125, 250ppm), consisting of 15 chicks (six treatment groups in 2×3 factorial design). Each of subgroups was replicated three times with each replicate including five chicks. The HS treatment significantly reduced the testicular spermatogenic cell counts, amount of testicular Bcl-2 (anti-apoptotic marker) and amount of AR. In addition, it significantly increased testicular lipid peroxidation, Bax (apoptotic marker) immunopositive staining, and the Bax/Bcl-2 ratio in conjunction with some histopathologic damage. Dietary supplementation of RO to diets of quail where the HS treatment was imposed alleviated HS-induced almost all negative changes such as increased testicular lipid peroxidation, decreased numbers of spermatogenic cells, and decreased amounts of Bcl-2 and AR, increased ratio of Bax/Bcl-2 and some testicular histopathologic lesion. In conclusion, dietary supplementation of RO for growing male Japanese quail reared in HS environmental conditions alleviates the HS-induced structural and functional damage by providing a decrease in lipid peroxidation.

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

    NASA Technical Reports Server (NTRS)

    Roth, Don J.; Rauser, Richard W.; Jacobson, nathan S.; Wincheski, Russell A.; Walker, James L.; Cosgriff, Laura A.

    2009-01-01

    In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter s thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using 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.

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

    PubMed

    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.

  12. Bee Products Prevent Agrichemical-Induced Oxidative Damage in Fish

    PubMed Central

    Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; Santos da Rosa, João Gabriel; 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. PMID:24098336

  13. Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation.

    PubMed

    Liu, Liang; Gao, Chao; Yao, Ping; Gong, Zhiyong

    2015-01-01

    A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved.

  14. Oxidative damage to macromolecules in the thyroid - experimental evidence

    PubMed Central

    2012-01-01

    Whereas oxidative reactions occur in all tissues and organs, the thyroid gland constitutes such an organ, in which oxidative processes are indispensable for thyroid hormone synthesis. It is estimated that huge amount of reactive oxygen species, especially of hydrogen peroxide (H2O2), are produced in the thyroid under physiological conditions, justifying the statement that the thyroid gland is an organ of “oxidative nature”. Apart from H2O2, also other free radicals or reactive species, formed from iodine or tyrosine residues, participate in thyroid hormone synthesis. Under physiological conditions, there is a balance between generation and detoxification of free radicals. Effective protective mechanisms, comprising antioxidative molecules and the process of compartmentalization of potentially toxic molecules, must have been developed in the thyroid to maintain this balance. However, with additional oxidative abuse caused by exogenous or endogenous prooxidants (ionizing radiation being the most spectacular), increased damage to macromolecules occurs, potentially leading to different thyroid diseases, cancer included. PMID:23270549

  15. Genetic engineering of AtAOX1a in Saccharomyces cerevisiae prevents oxidative damage and maintains redox homeostasis.

    PubMed

    Vishwakarma, Abhaypratap; Dalal, Ahan; Tetali, Sarada Devi; Kirti, Pulugurtha Bharadwaja; Padmasree, Kollipara

    2016-02-01

    This study aimed to validate the physiological importance of Arabidopsis thaliana alternative oxidase 1a (AtAOX1a) in alleviating oxidative stress using Saccharomyces cerevisiae as a model organism. The AOX1a transformant (pYES2AtAOX1a) showed cyanide resistant and salicylhydroxamic acid (SHAM)-sensitive respiration, indicating functional expression of AtAOX1a in S. cerevisiae. After exposure to oxidative stress, pYES2AtAOX1a showed better survival and a decrease in reactive oxygen species (ROS) when compared to S. cerevisiae with empty vector (pYES2). Furthermore, pYES2AtAOX1a sustained growth by regulating GPX2 and/or TSA2, and cellular NAD (+)/NADH ratio. Thus, the expression of AtAOX1a in S. cerevisiae enhances its respiratory tolerance which, in turn, maintains cellular redox homeostasis and protects from oxidative damage.

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

    PubMed

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

    2001-01-01

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

  17. Reduction in oxidatively generated DNA damage following smoking cessation

    PubMed Central

    2011-01-01

    Background Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking. Methods Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(TgpA)]; formamide breakdown of pyrimidine bases [d(TgpA)]; 8-oxo-7,8-dihydroguanine [d(Gh)]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition. Results Overall time effects for the d(TgpA) (χ2(3) = 8.068, p < 0.045), d(PfpA) (χ2(3) = 8.477, p < 0.037), and d(Gh) (χ2(3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(TgpA) and d(PfpA) lesions show relatively greater rebound at Week 16 compared to the d(Gh) lesion (88% of baseline for d(TgpA), 64% of baseline for d(PfpA), vs 46% of baseline for d(Gh)). Conclusions Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis. PMID:21569419

  18. Transgenic Mouse Model for Reducing Oxidative Damage in Bone

    NASA Technical Reports Server (NTRS)

    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

  19. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    SciTech Connect

    Arab, Hany H.; El-Sawalhi, Maha M.

    2013-04-15

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of

  20. Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation.

    PubMed

    Huang, Eng-Yen; Wang, Feng-Sheng; Chen, Yu-Min; Chen, Yi-Fan; Wang, Chung-Chi; Lin, I-Hui; Huang, Yu-Jie; Yang, Kuender D

    2014-10-30

    Amifostine (AM) is a radioprotector that scavenges free radicals and is used in patients undergoing radiotherapy. p53 has long been implicated in cell cycle arrest for cellular repair after radiation exposure. We therefore investigated the protective p53-dependent mechanism of AM on small bowel damage after lethal whole-abdominal irradiation (WAI). AM increased both the survival rate of rats and crypt survival following lethal 18 Gy WAI. The p53 inhibitor PFT-α compromised AM-mediated effects when administered prior to AM administration. AM significantly increased clonogenic survival in IEC-6 cells expressing wild type p53 but not in p53 knockdown cells. AM significantly increased p53 nuclear accumulation and p53 tetramer expression before irradiation through the inhibition of p53 degradation. AM inhibited p53 interactions with MDM2 but enhanced p53 interactions with 14-3-3σ. Knockdown of 14-3-3σ also compromised the effect of AM on clonogenic survival and p53 nuclear accumulation in IEC-6 cells. For the first time, our data reveal that AM alleviates lethal small bowel damage through the induction of 14-3-3σ and subsequent accumulation of p53. Enhancement of the p53/14-3-3σ interaction results in p53 tetramerization in the nucleus that rescues lethal small bowel damage.

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

    PubMed

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

    2003-08-01

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

  2. Dietary Saccharomyces cerevisiae Cell Wall Extract Supplementation Alleviates Oxidative Stress and Modulates Serum Amino Acids Profiles in Weaned Piglets

    PubMed Central

    Yu, Lei; Martínez, Yordan

    2017-01-01

    This research aims to evaluate the effects of dietary supplementation with Saccharomyces cerevisiae cell wall extract (SCCWE) on growth performance, oxidative stress, intestinal morphology, and serum amino acid concentration in weaned piglets. Utilizing a completely randomized design, 40 healthy piglets weaned at 21 d were grouped into 4 experimental treatments with 10 pigs per treatment group. Treatments consisted of a basal diet (T0), a basal diet with a 0.05% SCCWE (T1), a basal diet with a 0.10% SCCWE (T2), and a basal diet with a 0.15% SCCWE (T3). SCCWE supplementation increased the average daily gain and final body weight compared with T0 (P < 0.05). SCCWE in T2 and T3 improved the average daily feed intake and decreased the feed/gain ratio compared with T1 and T2 (P < 0.05). SCCWE decreased serum malondialdehyde (MDA) and increased activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) significantly compared to T0 (P < 0.05). SCCWE increased the concentration of Ile compared to T0 (P < 0.05). Moreover, the concentrations of Leu, Phe, and Arg were higher in T2 and T3 (P < 0.05). These findings indicate beneficial effects of SCCWE supplementation on growth performance, the concentration of some essential amino acids, and alleviation of oxidative stress in weaned piglets. PMID:28386308

  3. Nitric Oxide Alleviates Salt Stress Inhibited Photosynthetic Performance by Interacting with Sulfur Assimilation in Mustard

    PubMed Central

    Fatma, Mehar; Masood, Asim; Per, Tasir S.; Khan, Nafees A.

    2016-01-01

    The role of nitric oxide (NO) and sulfur (S) on stomatal responses and photosynthetic performance was studied in mustard (Brassica juncea L.) in presence or absence of salt stress. The combined application of 100 μM NO (as sodium nitroprusside) and 200 mg S kg−1 soil (S) more prominently influenced stomatal behavior, photosynthetic and growth performance both in the absence and presence of salt stress. The chloroplasts from salt-stressed plants had disorganized chloroplast thylakoids, but combined application of NO and S resulted in well-developed chloroplast thylakoids and properly stacked grana. The leaves from plants receiving NO plus S exhibited lower superoxide ion accumulation under salt stress than the plants receiving NO or S. These plants also exhibited increased activity of ATP-sulfurylase (ATPS), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) and optimized NO generation that helped in minimizing oxidative stress. The enhanced S-assimilation of these plants receiving NO plus S resulted in increased production of cysteine (Cys) and reduced glutathione (GSH). These findings indicated that NO influenced photosynthesis under salt stress by regulating oxidative stress and its effects on S-assimilation, an antioxidant system and NO generation. The results suggest that NO improves photosynthetic performance of plants grown under salt stress more effectively when plants received S. PMID:27200007

  4. Olanzapine alleviates oxidative stress in the liver of socially isolated rats.

    PubMed

    Stanisavljevic, Andrijana; Peric, Ivana; Pantelic, Marija; Filipovic, Dragana M

    2016-12-22

    Olanzapine, an antipsychotic drug, is used to treat depressive disorder, but its effects on the liver, the main site of drug metabolism, still remain elusive. We studied the effects of 3 weeks of olanzapine treatment (7.5 mg/kg per day) on the malondialdehyde (MDA) and protein carbonyl (PCO) contents, protein expression of copper/zinc superoxide dismutase (CuZnSOD), and activity of total superoxide dismutase (SOD), as well as catalase (CAT) protein expression and activity levels in the liver cytosol of rats exposed to 6 weeks of chronic social isolation (CSIS), which causes depressive- and anxiety-like behaviors. Increased cytosolic MDA in CSIS rats (vehicle- or olanzapine-treated) indicated hepatic oxidative stress. Increase in PCO and CAT activity associated with unchanged total SOD activity following CSIS also confirm the presence of oxidative stress. Chronic olanzapine treatment in CSIS prevented increase in PCO without an effect on MDA content. Increased SOD activity in olanzapine-treated (controls and CSIS) groups compared with corresponding vehicle-treated groups and decreased CAT activity in olanzapine-treated CSIS rats compared with vehicle-treated CSIS group was found. The data suggest that chronic olanzapine treatment has a protective effect on hepatic protein oxidation and improves antioxidant defense. The beneficial effects of olanzapine may be due to its free radical scavenging properties and antioxidant activity.

  5. Ageing-Associated Oxidative Stress and Inflammation Are Alleviated by Products from Grapes

    PubMed Central

    Petersen, K. S.

    2016-01-01

    Advanced age is associated with increased incidence of a variety of chronic disease states which share oxidative stress and inflammation as causative role players. Furthermore, data point to a role for both cumulative oxidative stress and low grade inflammation in the normal ageing process, independently of disease. Therefore, arguably the best route with which to address premature ageing, as well as age-associated diseases such as diabetes, cardiovascular disease, and dementia, is preventative medicine aimed at modulation of these two responses, which are intricately interlinked. In this review, we provide a detailed account of the literature on the communication of these systems in the context of ageing, but with inclusion of relevant data obtained in other models. In doing so, we attempted to more clearly elucidate or identify the most probable cellular or molecular targets for preventative intervention. In addition, given the absence of a clear pharmaceutical solution in this context, together with the ever-increasing consumer bias for natural medicine, we provide an overview of the literature on grape (Vitis vinifera) derived products, for which beneficial effects are consistently reported in the context of both oxidative stress and inflammation. PMID:27034739

  6. Choreography of oxidative damage repair in mammalian genomes.

    PubMed

    Mitra, Sankar; Izumi, Tadahide; Boldogh, Istvan; Bhakat, Kishor K; Hill, Jeff W; Hazra, Tapas K

    2002-07-01

    The lesions induced by reactive oxygen species in both nuclear and mitochondrial genomes include altered bases, abasic (AP) sites, and single-strand breaks, all repaired primarily via the base excision repair (BER) pathway. Although the basic BER process (consisting of five sequential steps) could be reconstituted in vitro with only four enzymes, it is now evident that repair of oxidative damage, at least in mammalian cell nuclei, is more complex, and involves a number of additional proteins, including transcription- and replication-associated factors. These proteins may be required in sequential repair steps in concert with other cellular changes, starting with nuclear targeting of the early repair enzymes in response to oxidative stress, facilitation of lesion recognition, and access by chromatin unfolding via histone acetylation, and formation of metastable complexes of repair enzymes and other accessory proteins. Distinct, specific subclasses of protein complexes may be formed for repair of oxidative lesions in the nucleus in transcribed vs. nontranscribed sequences in chromatin, in quiescent vs. cycling cells, and in nascent vs. parental DNA strands in replicating cells. Characterizing the proteins for each repair subpathway, their signaling-dependent modifications and interactions in the nuclear as well as mitochondrial repair complexes, will be a major focus of future research in oxidative damage repair.

  7. Measurement of oxidatively generated base damage in cellular DNA.

    PubMed

    Cadet, Jean; Douki, Thierry; Ravanat, Jean-Luc

    2011-06-03

    This survey focuses on the critical evaluation of the main methods that are currently available for monitoring single and complex oxidatively generated damage to cellular DNA. Among chromatographic methods, HPLC-ESI-MS/MS and to a lesser extent HPLC-ECD which is restricted to a few electroactive nucleobases and nucleosides are appropriate for measuring the formation of single and clustered DNA lesions. Such methods that require optimized protocols for DNA extraction and digestion are sensitive enough for measuring base lesions formed under conditions of severe oxidative stress including exposure to ionizing radiation, UVA light and high intensity UVC laser pulses. In contrast application of GC-MS and HPLC-MS methods that are subject to major drawbacks have been shown to lead to overestimated values of DNA damage. Enzymatic methods that are based on the use of DNA repair glycosylases in order to convert oxidized bases into strand breaks are suitable, even if they are far less specific than HPLC methods, to deal with low levels of single modifications. Several other methods including immunoassays and (32)P-postlabeling methods that are still used suffer from drawbacks and therefore are not recommended. Another difficult topic is the measurement of oxidatively generated clustered DNA lesions that is currently achieved using enzymatic approaches and that would necessitate further investigations.

  8. Exposure to benzene metabolites causes oxidative damage in Saccharomyces cerevisiae.

    PubMed

    Raj, Abhishek; Nachiappan, Vasanthi

    2016-06-01

    Hydroquinone (HQ) and benzoquinone (BQ) are known benzene metabolites that form reactive intermediates such as reactive oxygen species (ROS). This study attempts to understand the effect of benzene metabolites (HQ and BQ) on the antioxidant status, cell morphology, ROS levels and lipid alterations in the yeast Saccharomyces cerevisiae. There was a reduction in the growth pattern of wild-type cells exposed to HQ/BQ. Exposure of yeast cells to benzene metabolites increased the activity of the anti-oxidant enzymes catalase, superoxide dismutase and glutathione peroxidase but lead to a decrease in ascorbic acid and reduced glutathione. Increased triglyceride level and decreased phospholipid levels were observed with exposure to HQ and BQ. These results suggest that the enzymatic antioxidants were increased and are involved in the protection against macromolecular damage during oxidative stress; presumptively, these enzymes are essential for scavenging the pro-oxidant effects of benzene metabolites.

  9. Tamoxifen inhibits mitochondrial oxidative stress damage induced by copper orthophenanthroline.

    PubMed

    Buelna-Chontal, Mabel; Hernández-Esquivel, Luz; Correa, Francisco; Díaz-Ruiz, Jorge Luis; Chávez, Edmundo

    2016-12-01

    In this work, we studied the effect of tamoxifen and cyclosporin A on mitochondrial permeability transition caused by addition of the thiol-oxidizing pair Cu(2+) -orthophenanthroline. The findings indicate that tamoxifen and cyclosporin A circumvent the oxidative membrane damage manifested by matrix Ca(2+) release, mitochondrial swelling, and transmembrane electrical gradient collapse. Furthermore, it was found that tamoxifen and cyclosporin A prevent the generation of TBARs promoted by Cu(2+) -orthophenanthroline, as well as the inactivation of the mitochondrial enzyme aconitase and disruption of mDNA. Electrophoretic analysis was unable to demonstrate a cross-linking reaction between membrane proteins. Yet, it was found that Cu(2+) -orthophenanthroline induced the generation of reactive oxygen species. It is thus plausible that membrane leakiness is due to an oxidative stress injury.

  10. Prevention of oxidative DNA damage in rats by brussels sprouts.

    PubMed

    Deng, X S; Tuo, J; Poulsen, H E; Loft, S

    1998-03-01

    The alleged cancer preventive effects of cruciferous vegetables could be related to protection from mutagenic oxidative DNA damage. We have studied the effects of Brussels sprouts, some non-cruciferous vegetables and isolated glucosinolates on spontaneous and induced oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in groups of 6-8 male Wistar rats. Excess oxidative DNA damage was induced by 2-nitropropane (2-NP 100 mg/kg). Four days oral administration of 3 g of cooked Brussels sprouts homogenate reduced the spontaneous urinary 8-oxodG excretion by 31% (p<0.05) whereas raw sprouts, beans and endive (1:1), isolated indolyl glucosinolates and breakdown products had no significant effect. An aqueous extract of cooked Brussels sprouts (corresponding to 6.7 g vegetable per day for 4 days) decreased the spontaneous 8-oxodG excretion from 92 +/- 12 to 52 +/- 15 pmol/24 h (p<0.05). After 2-NP administration the 8-oxodG excretion was increased to 132 +/- 26 pmol/24 h (p<0.05) whereas pretreatment with the sprouts extract reduced this to 102 +/- 30 pmol/24 h (p<0.05). The spontaneous level of 8-oxodG in nuclear DNA from liver and bone marrow was not significantly affected by the sprouts extract whereas the level decreased by 27% in the kidney (p<0.05). In the liver 2-NP increased the 8-oxodG levels in nuclear DNA 8.7 and 3.8 times (p<0.05) 6 and 24 h after dose, respectively. The sprouts extract reduced this increase by 57% (p<0.05) at 6 h whereas there was no significant effect at 24 h. In the kidneys 2-NP increased the 8-oxodG levels 2.2 and 1.2 times (p<0.05) 6 and 24 h after dose, respectively. Pretreatment with the sprouts extract abolished these increases (p<0.05). Similarly, in the bone marrow the extract protected completely (p<0.05) against a 4.9-fold 2-NP induced increase (p<0.05) in the 8-oxodG level. These findings demonstrate that cooked Brussels sprouts contain bioactive substance(s) with a potential for reducing the physiological

  11. Chronic Oral Pelargonidin Alleviates Streptozotocin-Induced Diabetic Neuropathic Hyperalgesia in Rat: Involvement of Oxidative Stress

    PubMed Central

    Mirshekar, Mohammadali; Roghani, Mehrdad; Khalili, Mohsen; Baluchnejadmojarad, Tourandokht; Arab Moazzen, Saiedeh

    2010-01-01

    Background: Diabetes mellitus in some clinical cases is accompanied with hyperalgesia. In this study, we evaluated the possible beneficial effect of chronic pelargonidin (PG) treatment on hyperalgesia in streptozotocin (STZ)-diabetic neuropathic rat. Methods: Male Wistar rats (n = 56) were divided into seven groups, i.e. control, diabetic, PG-treated control, PG (single- and multiple-dose)-treated diabetic, and sodium salicylate-treated control and diabetics. For induction of diabetes, STZ was injected i.p. at a single dose of 60 mg/kg. PG was orally administered at a dose of 10 mg/kg once and/or on alternate days for 8 weeks; 1 week after diabetes induction. After two months, hyperalgesia was assessed using standard formalin and hot tail immersion tests. Meanwhile, markers of oxidative stress in brain were measured. One-way analysis of variance was used for statistical analysis of the data. Results: Diabetic rats showed a marked chemical and thermal hyperalgesia, indicating that development of diabetic neuropathy and PG treatment (especially multiple-doses) significantly ameliorated the alteration in hyperalgesia (P<0.05-0.01) in diabetic rats as compared to untreated diabetics. PG (multiple doses) also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation and non-significantly reversed elevation of nitrite level and reduction of antioxidant defensive enzyme superoxide dismutase. Conclusion: These results clearly suggest that PG prevents diabetic neuropathic hyperalgesia through attenuation of oxidative stress. PMID:20683496

  12. Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function.

    PubMed

    Bi, Wei; Bi, Yue; Gao, Xiang; Li, Pengfei; Hou, Shanshan; Zhang, Yanrong; Bammert, Cathy; Jockusch, Steffen; Legalley, Thomas D; Michael Gibson, K; Bi, Lanrong

    2017-05-01

    Mitochondrial oxidative damage contributes to a wide range of pathologies including ischemia/reperfusion injury. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel indole-TEMPO conjugates that manifested good anti-inflammatory properties in a murine model of xylene-induced ear edema. We have demonstrated that these compounds can protect cells from simulated ischemia/reperfusion (s-I/R)-induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, we have demonstrated that indole-TEMPO conjugates can attenuate organ damage induced in rodents via intestinal I/R injury. We therefore propose that the pharmacological profile and mechanism of action of these indole-TEMPO conjugates involve convergent roles, including the ability to decrease free radical production via lipid peroxidation which couples to an associated decrease in ROS-mediated activation of the inflammatory process. We further hypothesize that the protective effects of indole-TEMPO conjugates partially reside in maintaining optimal mitochondrial function.

  13. Graphene oxide alleviates the ecotoxicity of copper on the freshwater microalga Scenedesmus obliquus.

    PubMed

    Hu, Changwei; Hu, Naitao; Li, Xiuling; Zhao, Yongjun

    2016-10-01

    The extensive industrial application of graphene oxide (GO), has increased its exposure risk to various aquatic organisms and its potential to affect the toxicity of other environmental pollutants. In this study, we investigated the combined toxicity of GO and copper on the freshwater microalga Scenedesmus obliquus, using the MIXTOX model. The effects of low concentration (1mg/L) exposure to GO were investigated with environmentally relevant concentrations of copper by using a 12-d subacute toxicity test, with pre- and post-GO treatment. Results showed that there were significant antagonistic effects between GO and copper on S. obliquus, and GO was found to reduce ecotoxicity of copper even at low and environmentally relevant concentrations (1mg/L).

  14. In vitro toxicity of iron oxide nanoparticle: oxidative damages on Hep G2 cells.

    PubMed

    Sadeghi, Leila; Tanwir, Farzeen; Yousefi Babadi, Vahid

    2015-02-01

    During the past years many studies have been done highlighting the great need for a more thorough understanding of cell-iron oxide nanoparticle interactions. To improve our knowledge in this field, there is a great need for standardized protocols that would allow to comparing the cytotoxic potential of any Fe2O3-NP type with previously studied particles. Several approaches are reported that several parameters which are of great importance for Fe2O3 nanoparticle induced toxicity. Nanoparticles because of their very small size can pass through the cell membrane and can make oxidative damage in all parts of the cells such as mitochondria, membrane, DNA due to high surface area. This study focuses on acute cytotoxicity of reactive oxygen species and DNA damaging effects of mentioned nanoparticles. Results showed increase of the oxidative damage leads cells to the apoptosis, therefore reduced cell viability. It is interesting that all of the results are concentration and time dependent.

  15. Transcription-coupled homologous recombination after oxidative damage.

    PubMed

    Wei, Leizhen; Levine, Arthur Samuel; Lan, Li

    2016-08-01

    Oxidative DNA damage induces genomic instability and may lead to mutagenesis and carcinogenesis. As severe blockades to RNA polymerase II (RNA POLII) during transcription, oxidative DNA damage and the associated DNA strand breaks have a profoundly deleterious impact on cell survival. To protect the integrity of coding regions, high fidelity DNA repair at a transcriptionally active site in non-dividing somatic cells, (i.e., terminally differentiated and quiescent/G0 cells) is necessary to maintain the sequence integrity of transcribed regions. Recent studies indicate that an RNA-templated, transcription-associated recombination mechanism is important to protect coding regions from DNA damage-induced genomic instability. Here, we describe the discovery that G1/G0 cells exhibit Cockayne syndrome (CS) B (CSB)-dependent assembly of homologous recombination (HR) factors at double strand break (DSB) sites within actively transcribed regions. This discovery is a challenge to the current dogma that HR occurs only in S/G2 cells where undamaged sister chromatids are available as donor templates.

  16. Aluminium phosphide-induced genetic and oxidative damages in vitro: Attenuation by Laurus nobilis L. leaf extract

    PubMed Central

    Türkez, Hasan; Toğar, Başak

    2013-01-01

    Objective: The present investigation was undertaken to assess the protective effect of Laurus nobilis leaf extract (LNE) against aluminum phosphide (AIP)-induced genotoxic and oxidative damages stress in cultured human blood cells in the presence of a metabolic activator (S9 mix). Materials and Methods: Sister chromatid exchange (SCE) and chromosome aberration (CA) assays were used to assess AlP-induced genotoxicity and to establish the protective effects of LNE. In addition, we determined total antioxidant capacity (TAC) and total oxidative status (TOS) levels in AlP and LNE treated cultures for biomonitoring the oxidative alterations. Results: There was significant increases (P < 0.05) in both SCE and CA frequencies of cultures treated with AlP as compared to controls. Our results also showed that AlP (58 mg/l) caused oxidative stress by altering TAC and TOS levels. However, co-application of LNE (25, 50, 100 and 200 mg/l) and AlP resulted in decreases of SCE, CA rates and TOS level and increases of TAC level as compared to the group treated with AlP alone. Conclusion: The preventive role of LNE in alleviating AlP-induced DNA and oxidative damages was indicated for the first time in the present study. PMID:23543905

  17. Selenomethionine alleviates AFB1-induced damage in primary chicken hepatocytes by inhibiting CYP450 1A5 expression via upregulated SelW expression.

    PubMed

    Chen, Xingxiang; Che, Chaoping; Korolchuk, Viktor I; Gan, Fang; Pan, Cuiling; Huang, Kehe

    2017-03-13

    This study aims to evaluate the protective effects of selenomethionine (SeMet) on Aflatoxin B1 (AFB1)-induced hepatotoxicity in primary chicken hepatocytes. Cell viability and lactic dehydrogenase activity assays revealed the dose-dependency of AFB1 toxicity to chicken hepatocytes. AFB1 concentrations above 0.05 μg/mL significantly reduced glutathione and total superoxide dismutase levels, as well as increased malondialdehyde concentration and cytochrome P450 enzyme 1A5 (CYP450 1A5) mRNA levels (P < 0.05). AFB1, however, did not affect CYP450 3A37 mRNA levels. Supplementation with 2 μM SeMet protected against AFB1-induced changes and significantly increased selenoprotein W (SelW) mRNA levels (P < 0.05). Additionally, SelW knockdown attenuated the protective effect of SeMet on AFB1-induced damage and significantly increased CYP450 1A5 expression (P < 0.05). Therefore, SeMet alleviates AFB1-induced damage in primary chicken hepatocytes by improving SelW expression, thus inhibiting CYP450 1A5 expression.

  18. Oxidant-induced DNA damage of target cells.

    PubMed Central

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

    1988-01-01

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

  19. Oxidative Damage in the Aging Heart: an Experimental Rat Model

    PubMed Central

    Marques, Gustavo Lenci; Neto, Francisco Filipak; Ribeiro, Ciro Alberto de Oliveira; Liebel, Samuel; de Fraga, Rogério; Bueno, Ronaldo da Rocha Loures

    2015-01-01

    Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID:27006709

  20. Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

    PubMed Central

    Zhang, Bin; Shen, Qiang; Chen, Yaping; Pan, Ruile; Kuang, Shihuan; Liu, Guiyan; Sun, Guibo; Sun, Xiaobo

    2017-01-01

    Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM. PMID:28287141

  1. Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy.

    PubMed

    Zhang, Bin; Shen, Qiang; Chen, Yaping; Pan, Ruile; Kuang, Shihuan; Liu, Guiyan; Sun, Guibo; Sun, Xiaobo

    2017-03-13

    Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM.

  2. Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway

    PubMed Central

    Li, Qing-rong; Wang, Zhuo; Zhou, Wei; Fan, Shou-rui; Ma, Run; Xue, Li; Yang, Lu; Li, Ya-shan; Tan, Hong-li; Shao, Qing-hua; Yang, Hong-ying

    2016-01-01

    Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway. PMID:27073391

  3. SOS processing of unique oxidative DNA damages in Escherichia coli.

    PubMed

    Laspia, M F; Wallace, S S

    1989-05-05

    phi X174 replicative form (RF) I transfecting DNA containing thymine glycols (5,6-dihydroxy-5,6-dihydrothymine), urea glycosides or apurinic (AP) sites was used to study SOS processing of unique DNA damages in Escherichia coli. All three lesions can be found in DNA damaged by chemical oxidants or radiation and are representative of several common structural modifications of DNA bases. When phi X DNA containing thymine glycols was transfected into host cells that were ultraviolet-irradiated to induce the SOS response, a substantial increase in survival was observed compared to transfection into uninduced hosts. Studies with mutants demonstrated that both the activated form of RecA and UmuDC proteins were required for this reactivation. In contrast, no increase in survival was observed when DNA containing urea glycosides or AP sites was transfected into ultraviolet-induced hosts. These data suggest that SOS-induced reactivation does not reflect a generalized repair system for all replication-blocking, lethal lesions but rather that the efficiency of reactivation is damage dependent. Further, we found that a significant fraction of potentially lethal thymine glycols could be ultraviolet-reactivated in an umuC lexA recA-independent manner, suggesting the existence of an as yet uncharacterized damage-inducible SOS-independent mode of thymine glycol repair.

  4. Hydrogen sulfide alleviates toxic effects of arsenate in pea seedlings through up-regulation of the ascorbate-glutathione cycle: Possible involvement of nitric oxide.

    PubMed

    Singh, Vijay Pratap; Singh, Samiksha; Kumar, Jitendra; Prasad, Sheo Mohan

    2015-06-01

    In plants, hydrogen sulfide (H2S) is an emerging novel signaling molecule that is involved in growth regulation and abiotic stress responses. However, little is known about its role in the regulation of arsenate (As(V)) toxicity. Therefore, hydroponic experiments were conducted to investigate whether sodium hydrosulfide (NaHS; a source of H2S) is involved in the regulation of As(V) toxicity in pea seedlings. Results showed that As(V) caused decreases in growth, photosynthesis (measured as chlorophyll fluorescence) and nitrogen content, which was accompanied by the accumulation of As. As(V) treatment also reduced the activities of cysteine desulfhydrase and nitrate reductase, and contents of H2S and nitric oxide (NO). However, addition of NaHS ameliorated As(V) toxicity in pea seedlings, which coincided with the increased contents of H2S and NO. The cysteine level was higher under As(V) treatment in comparison to all other treatments (As-free; NaHS; As(V)+NaHS). The content of reactive oxygen species (ROS) and damage to lipids, proteins and membranes increased by As(V) while NaHS alleviated these effects. Enzymes of the ascorbate-glutathione cycle (AsA-GSH cycle) showed inhibition of their activities following As(V) treatment while their activities were increased by application of NaHS. The redox status of ascorbate and glutathione was disturbed by As(V) as indicated by a steep decline in their reduced/oxidized ratios. However, simultaneous NaHS application restored the redox status of the ascorbate and glutathione pools. The results of this study demonstrated that H2S and NO might both be involved in reducing the accumulation of As and triggering up-regulation of the AsA-GSH cycle to counterbalance ROS-mediated damage to macromolecules. Furthermore, the results suggest a crucial role of H2S in plant priming, and in particular for pea seedlings in mitigating As(V) stress.

  5. Red photon treatment inhibits apoptosis via regulation of bcl-2 proteins and ROS levels, alleviating hypoxic-ischemic brain damage.

    PubMed

    Jiang, W; Chen, L; Zhang, X J; Chen, J; Li, X C; Hou, W S; Xiao, N

    2014-05-30

    Therapeutic options for hypoxic-ischemic brain damage (HIBD) are scarce and inefficient. Recently, many studies have demonstrated that red photon plays an important role in anti-inflammatory processes as well as apoptosis, the main trait of HIBD. In this study, we investigated whether red photon can protect from HIBD in SD rats and oxygen-glucose deprivation (OGD) in PC12 cells. Apoptosis, mitochondrial transmembrane potential (MMP), and reactive oxygen species (ROS) rates were assessed in PC12 cells. We found that 6-h irradiation resulted in decreased MMP, ROS and apoptosis rates, although these changes were reversible with prolonged irradiation. Importantly, these effects were sustained for 2-8h upon quenching of the red photon. Similar trends were observed for protein and mRNA expression of bax and bcl-2, with short-term irradiation (6h) inhibiting apoptosis in PC12 Cells. However, long-term (>6h) irradiation caused cell damage. In vivo experiments, bax mRNA and protein levels were reduced after 7days in HIBD model rats treated with red photon, in contrast to bcl-2. Furthermore, we found that bax and bcl-2 were mainly expressed in pyramidal cells of the hippocampus CA1 and CA3. Importantly, Morris Water Maze test results revealed an improvement in learning ability and spatial memory in rats after irradiation. Overall, our data showed that short-term irradiation with red photon in the acute phase inhibits the mitochondrial apoptotic pathway via regulation of bcl-2-related proteins and reduction of ROS levels, thereby decreasing apoptosis in nerve cells and improving the neurological prognosis of HIBD.

  6. Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect

    PubMed Central

    Ben Boujema, Meric; Laboureyras, Emilie; Pype, Jan; Bessière, Baptiste; Simonnet, Guy

    2015-01-01

    BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury. OBJECTIVE: Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N2O concentration and the shortest time of N2O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2O with gabapentin, a reference drug used in human neuropathic pain relief. METHODS: Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats. RESULTS: Among the various N2O concentrations tested, which ranged from 25% to 50%, only 50% N2O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg/kg to 300 mg/kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N2O. CONCLUSIONS: These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies. PMID:26371891

  7. Green tea catechins, alleviate hepatic lipidemic-oxidative injury in Wistar rats fed an atherogenic diet.

    PubMed

    Ramesh, E; Jayakumar, T; Elanchezhian, R; Sakthivel, M; Geraldine, P; Thomas, P A

    2009-06-15

    In the present study, the efficacy of green tea catechins (GTC from the plant Camellia sinensis), with epigallocatechin gallate (EGCG), as the major component, was studied in relation to hepatic oxidative abnormalities in atherosclerotic rats. When male albino Wistar rats were fed an atherogenic diet for 30 days and then treated with saline for 7 or 15 days, there was a significant decline in hepatic mean activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase), and non-enzymatic antioxidants (reduced glutathione, vitamins C and E) while there was a significant elevation in the mean level of hepatic malondialdehyde (MDA), in comparison to the values noted in control rats fed a normal diet. In addition, a concomitant increase in the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) was noted, when compared to the values in control rats. Following intraperitoneal administration of GTC (100mg/kg) for 7 or 15 days to rats fed the atherogenic diet, significantly higher mean activities of enzymatic and non-enzymatic antioxidants and lower mean levels of MDA in hepatic tissue and lower mean activities of AST, ALT, ALP and LDH in serum were observed, compared to the values in the rats fed the atherogenic diet and treated with saline. Histopathological studies were performed to provide direct evidence of the atherogenic diet-induced hepatic changes and of the hepatoprotective effect of GTC. These results suggest that EGCG as a major component of green tea catechins may protect against the hepatic abnormalities occurring in Wistar rats fed an atherogenic diet.

  8. Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced Hepatotoxicity in Rats.

    PubMed

    El-Hosseiny, L S; Alqurashy, N N; Sheweita, S A

    2016-06-01

    Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liver injury. The combination of amoxicillin with clavulanic acid is commonly cited in such cases. Accordingly, the present study investigated the potential hepatoprotective and in vivo antioxidant efficacy of sage essential oil in Co-amoxiclav induced hepatotoxicity in rats. Sage essential oil was hydrodistilled from the aerial parts of Salvia officinalis L. and its compositional analysis was characterized by Gas chromatography-Mass spectroscopy. Rats were treated singly or concomitantly with Co-amoxiclav and sage essential oil for a period of seven days. The major components of sage oil as identified by GC-MS were 1,8-cineole, β-pinene, camphor, β-caryophyllene, α-pinene and α-caryophyllene comprising 26.3%, 14.4%, 10.9%, 7.8%, 6% and 2.5% respectively. The in vivo exposure of rats to Co-amoxiclav resulted in hepatotoxicity biochemically evidenced by the significant elevation of serum AST, ALT, ALP, γ-GT, total bilirubin and histologically conveyed by hydropic, inflammatory and cholestatic changes in rats' liver. Oxidative stress mediated the hepatic injury as indicated by the significant escalation in lipid peroxidation, as well as, the significant depletion of both glutathione level and glutathione dependent enzymes' activities. The concomitant administration of sage essential oil with Co-amoxiclav exerted a hepatoprotective effect via inducing an in vivo antioxidant defense response eventually regressing, to some extent, the hepatoarchitectural changes induced by Co-amoxiclav. Results suggest that sage essential oil is a potential candidate for counteracting hepatic injury associating Co-amoxiclav and this effect is in part related to the complexity of its chemical composition.

  9. Nitric oxide-releasing chitosan nanoparticles alleviate the effects of salt stress in maize plants.

    PubMed

    Oliveira, Halley C; Gomes, Bruna C R; Pelegrino, Milena T; Seabra, Amedea B

    2016-12-30

    Nitric oxide (NO) is a signaling molecule involved in plant response to various abiotic stresses. However, the application of NO donors in agriculture is hampered by the instability of these compounds. Despite the successful uses of NO-releasing nanoparticles for biomedical purposes and the variety of nanomaterials developed as carrier systems of agrochemicals, the potential applications of nanocarriers for NO delivery in plants have not yet been tested. Herein, we report the synthesis and characterization of chitosan nanoparticles (CS NPs) containing the NO donor S-nitroso-mercaptosuccinic acid (S-nitroso-MSA). The efficiency of these NO-releasing NPs in mitigating the deleterious effects of salinity on maize plants was compared to that of the non-encapsulated NO donor. The NPs were synthesized through ionotropic gelation process, and mercaptosuccinic acid (MSA), the NO donor precursor, was encapsulated into CS NPs (91.07% encapsulation efficiency). Free thiol groups of MSA-CS NPs were nitrosated, leading to S-nitroso-MSA-CS NPs (NO-releasing NPs). The incorporation of S-nitroso-MSA into CS NPs allowed a sustained NO release. Treatments of salt-stressed maize plants with S-nitroso-MSA-CS NPs resulted in a higher leaf S-nitrosothiols content compared to that of free S-nitroso-MSA. Moreover, S-nitroso-MSA-CS NPs were more efficient than was the free NO donor in the amelioration of the deleterious effects of salinity in photosystem II activity, chlorophyll content and growth of maize plants because the protective action of the nanoencapsulated S-nitroso-MSA was achieved at lower dosages. Overall, these results demonstrate the positive impact of S-nitroso-MSA nanoencapsulation in increasing NO bioactivity in maize plants under salt stress.

  10. Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced Hepatotoxicity in Rats

    PubMed Central

    El-Hosseiny, L. S.; Alqurashy, N. N.; Sheweita, S. A.

    2016-01-01

    Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liver injury. The combination of amoxicillin with clavulanic acid is commonly cited in such cases. Accordingly, the present study investigated the potential hepatoprotective and in vivo antioxidant efficacy of sage essential oil in Co-amoxiclav induced hepatotoxicity in rats. Sage essential oil was hydrodistilled from the aerial parts of Salvia officinalis L. and its compositional analysis was characterized by Gas chromatography-Mass spectroscopy. Rats were treated singly or concomitantly with Co-amoxiclav and sage essential oil for a period of seven days. The major components of sage oil as identified by GC-MS were 1,8-cineole, β-pinene, camphor, β-caryophyllene, α-pinene and α-caryophyllene comprising 26.3%, 14.4%, 10.9%, 7.8%, 6% and 2.5% respectively. The in vivo exposure of rats to Co-amoxiclav resulted in hepatotoxicity biochemically evidenced by the significant elevation of serum AST, ALT, ALP, γ-GT, total bilirubin and histologically conveyed by hydropic, inflammatory and cholestatic changes in rats’ liver. Oxidative stress mediated the hepatic injury as indicated by the significant escalation in lipid peroxidation, as well as, the significant depletion of both glutathione level and glutathione dependent enzymes’ activities. The concomitant administration of sage essential oil with Co-amoxiclav exerted a hepatoprotective effect via inducing an in vivo antioxidant defense response eventually regressing, to some extent, the hepatoarchitectural changes induced by Co-amoxiclav. Results suggest that sage essential oil is a potential candidate for counteracting hepatic injury associating Co-amoxiclav and this effect is in part related to the complexity of its chemical composition. PMID:27493593

  11. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    SciTech Connect

    Milatovic, Dejan; Yu, Yingchun

    2009-10-15

    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{sub 2}-isoprostanes (F{sub 2}-IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 {mu}M Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E{sub 2} (PGE{sub 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{sub 2}-IsoPs and PGE{sub 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. Treatment with a nitric oxide-donating NSAID alleviates functional muscle ischemia in the mouse model of Duchenne muscular dystrophy.

    PubMed

    Thomas, Gail D; Ye, Jianfeng; De Nardi, Claudio; Monopoli, Angela; Ongini, Ennio; Victor, Ronald G

    2012-01-01

    In patients with Duchenne muscular dystrophy (DMD) and the standard mdx mouse model of DMD, dystrophin deficiency causes loss of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma, producing functional ischemia when the muscles are exercised. We asked if functional muscle ischemia would be eliminated and normal blood flow regulation restored by treatment with an exogenous nitric oxide (NO)-donating drug. Beginning at 8 weeks of age, mdx mice were fed a standard diet supplemented with 1% soybean oil alone or in combination with a low (15 mg/kg) or high (45 mg/kg) dose of HCT 1026, a NO-donating nonsteroidal anti-inflammatory agent which has previously been shown to slow disease progression in the mdx model. After 1 month of treatment, vasoconstrictor responses to intra-arterial norepinephrine (NE) were compared in resting and contracting hindlimbs. In untreated mdx mice, the usual effect of muscle contraction to attenuate NE-mediated vasoconstriction was impaired, resulting in functional ischemia: NE evoked similar decreases in femoral blood flow velocity and femoral vascular conductance (FVC) in the contracting compared to resting hindlimbs (ΔFVC contraction/ΔFVC rest=0.88 ± 0.03). NE-induced functional ischemia was unaffected by low dose HCT 1026 (ΔFVC ratio=0.92 ± 0.04; P>0.05 vs untreated), but was alleviated by the high dose of the drug (ΔFVC ratio=0.22 ± 0.03; P<0.05 vs untreated or low dose). The beneficial effect of high dose HCT 1026 was maintained with treatment up to 3 months. The effect of the NO-donating drug HCT 1026 to normalize blood flow regulation in contracting mdx mouse hindlimb muscles suggests a putative novel treatment for DMD. Further translational research is warranted.

  13. Resveratrol protects mouse oocytes from methylglyoxal-induced oxidative damage.

    PubMed

    Liu, Yu; He, Xiao-Qin; Huang, Xin; Ding, Lu; Xu, Lin; Shen, Yu-Ting; Zhang, Fei; Zhu, Mao-Bi; Xu, Bai-Hui; Qi, Zhong-Quan; Wang, Hai-Long

    2013-01-01

    Methylglyoxal, a reactive dicarbonyl compound, is mainly formed from glycolysis. Methylglyoxal can lead to the dysfunction of mitochondria, the depletion of cellular anti-oxidation enzymes and the formation of advanced glycation ends. Previous studies showed that the accumulation of methylglyoxal and advanced glycation ends can impair the oocyte maturation and reduce the oocyte quality in aged and diabetic females. In this study, we showed that resveratrol, a kind of phytoalexin found in the skin of grapes, red wine and other botanical extracts, can alleviate the adverse effects caused by methylglyoxal, such as inhibition of oocyte maturation and disruption of spindle assembly. Besides, methylglyoxal-treated oocytes displayed more DNA double strands breaks and this can also be decreased by treatment of resveratrol. Further investigation of these processes revealed that methylglyoxal may affect the oocyte quality by resulting in excessive reactive oxygen species production, aberrant mitochondrial distribution and high level lipid peroxidation, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can protect the oocytes from methylglyoxal-induced cytotoxicity and this was mainly through the correction of the abnormity of cellular reactive oxygen species metabolism.

  14. Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis

    PubMed Central

    Martínez-Espinosa, Rodrigo; Argüello-García, Raúl; Saavedra, Emma; Ortega-Pierres, Guadalupe

    2015-01-01

    The control of Giardia duodenalis infections is carried out mainly by drugs, among these albendazole (ABZ) is commonly used. Although the cytotoxic effect of ABZ usually involves binding to β-tubulin, it has been suggested that oxidative stress may also play a role in its parasiticidal mechanism. In this work the effect of ABZ in Giardia clones that are susceptible or resistant to different concentrations (1.35, 8, and 250 μM) of this drug was analyzed. Reactive oxygen species (ROS) were induced by ABZ in susceptible clones and this was associated with a decrease in growth that was alleviated by cysteine supplementation. Remarkably, ABZ-resistant clones exhibited partial cross-resistance to H2O2, whereas a Giardia H2O2-resistant strain can grow in the presence of ABZ. Lipid oxidation and protein carbonylation in ABZ-treated parasites did not show significant differences as compared to untreated parasites; however, ABZ induced the formation of 8OHdG adducts and DNA degradation, indicating nucleic acid oxidative damage. This was supported by observations of histone H2AX phosphorylation in ABZ-susceptible trophozoites treated with 250 μM ABZ. Flow cytometry analysis showed that ABZ partially arrested cell cycle in drug-susceptible clones at G2/M phase at the expense of cells in G1 phase. Also, ABZ treatment resulted in phosphatidylserine exposure on the parasite surface, an event related to apoptosis. All together these data suggest that ROS induced by ABZ affect Giardia genetic material through oxidative stress mechanisms and subsequent induction of apoptotic-like events. PMID:26300866

  15. Role of Oxidative Damage in Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

  16. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    PubMed

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate.

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

    PubMed Central

    Warleta, Fernando; Quesada, Cristina Sánchez; Campos, María; Allouche, Yosra; Beltrán, Gabriel; Gaforio, José J.

    2011-01-01

    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. PMID:22254082

  18. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    PubMed Central

    Suntres, Zacharias E.

    2011-01-01

    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. PMID:21876690

  19. Hydroxytyrosol protects against oxidative DNA damage in human breast cells.

    PubMed

    Warleta, Fernando; Quesada, Cristina Sánchez; Campos, María; Allouche, Yosra; Beltrán, Gabriel; Gaforio, José J

    2011-10-01

    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.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

    Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. Methods: The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2- scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays. Results: Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2- scavenging, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form. PMID:27478791

  2. Oxidative damage involves in the inhibitory effect of nitric oxide on spore germination of Penicillium expansum.

    PubMed

    Lai, Tongfei; Li, Boqiang; Qin, Guozheng; Tian, Shiping

    2011-01-01

    The effects of nitric oxide (NO) on spore germination of Penicillium expansum were investigated and a possible mechanism was evaluated. The results indicated that NO released by sodium nitroprusside (SNP) significantly suppressed fungal growth. With the use of an oxidant sensitive probe and Western blot analysis, an increased level of intracellular reactive oxygen species (ROS) and enhanced carbonylation damage were detected in spores of P. expansum under NO stress. Exogenous superoxide dismutase (SOD) and ascorbic acid (Vc) could increase the resistance of the spore to the inhibitory effect of NO. The activities of SOD and catalase (CAT), as well as ATP content in spores under NO stress were also lower than those in the control. We suggest that NO in high concentration induces the generation of ROS which subsequently causes severe oxidative damage to proteins crucial to the process of spore germination of P. expansum.

  3. Pathophysiology of Bronchoconstriction: Role of Oxidatively Damaged DNA Repair

    PubMed Central

    Bacsi, Attila; Pan, Lang; Ba, Xueqing; Boldogh, Istvan

    2016-01-01

    Purpose of review To provide an overview on the present understanding of roles of oxidative DNA damage repair in cell signaling underlying bronchoconstriction common to, but not restricted to various forms of asthma and chronic obstructive pulmonary disease Recent findings Bronchoconstriction is a tightening of smooth muscle surrounding the bronchi and bronchioles with consequent wheezing and shortness of breath. Key stimuli include air pollutants, viral infections, allergens, thermal and osmotic changes, and shear stress of mucosal epithelium, triggering a wide range of cellular, vascular and neural events. Although activation of nerve fibers, the role of G-proteins, protein kinases and Ca++, and molecular interaction within contracting filaments of muscle are well defined, the overarching mechanisms by which a wide range of stimuli initiate these events are not fully understood. Many, if not all, stimuli increase levels of reactive oxygen species (ROS), which are signaling and oxidatively modifying macromolecules, including DNA. The primary ROS target in DNA is guanine, and 8-oxoguanine is one of the most abundant base lesions. It is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair processes. The product, free 8-oxoG base, is bound by OGG1 with high affinity, and the complex then functions as an activator of small GTPases, triggering pathways for inducing gene expression and contraction of intracellular filaments in mast and smooth muscle cells. Summary Oxidative DNA damage repair-mediated cell activation signaling result in gene expression that “primes” the mucosal epithelium and submucosal tissues to generate mediators of airway smooth muscle contractions. PMID:26694039

  4. Silicon improves seed germination and alleviates oxidative stress of bud seedlings in tomato under water deficit stress.

    PubMed

    Shi, Yu; Zhang, Yi; Yao, Hejin; Wu, Jiawen; Sun, Hao; Gong, Haijun

    2014-05-01

    The beneficial effects of silicon on plant growth and development under drought have been widely reported. However, little information is available on the effects of silicon on seed germination under drought. In this work, the effects of exogenous silicon (0.5 mM) on the seed germination and tolerance performance of tomato (Solanum lycopersicum L.) bud seedlings under water deficit stress simulated by 10% (w/v) polyethylene glycol (PEG-6000) were investigated in four cultivars ('Jinpengchaoguan', 'Zhongza No.9', 'Houpi L402' and 'Oubao318'). The results showed that the seed germination percentage was notably decreased in the four cultivars under water stress, and it was significantly improved by added silicon. Compared with the non-silicon treatment, silicon addition increased the activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the production of superoxide anion (O2·) and hydrogen peroxide (H2O2) in the radicles of bud seedlings under water stress. Addition of silicon decreased the total phenol concentrations in radicles under water stress, which might contribute to the decrease of peroxidase (POD) activity, as observed in the in vivo and in vitro experiments. The decrease of POD activity might contribute to a less accumulation of hydroxyl radical (·OH) under water stress. Silicon addition also decreased the concentrations of malondialdehyde (MDA) in the radicles under stress, indicating decreased lipid peroxidation. These results suggest that exogenous silicon could improve seed germination and alleviate oxidative stress to bud seedling of tomato by enhancing antioxidant defense. The positive effects of silicon observed in a silicon-excluder also suggest the active involvement of silicon in biochemical processes in plants.

  5. Inhaled nitric oxide alleviates hyperoxia suppressed phosphatidylcholine synthesis in endotoxin-induced injury in mature rat lungs

    PubMed Central

    Gong, Xiaohui; Guo, Chunbao; Huang, Shibing; Sun, Bo

    2006-01-01

    Background We investigated efficacy of inhaled nitric oxide (NO) in modulation of metabolism of phosphatidylcholine (PC) of pulmonary surfactant and in anti-inflammatory mechanism of mature lungs with inflammatory injury. Methods Healthy adult rats were divided into a group of lung inflammation induced by i.v. lipopolysaccharides (LPS) or a normal control (C) for 24 h, and then exposed to: room air (Air), 95% oxygen (O), NO (20 parts per million, NO), both O and NO (ONO) as subgroups, whereas [3H]-choline was injected i.v. for incorporation into PC of the lungs which were processed subsequently at 10 min, 4, 8, 12 and 24 h, respectively, for measurement of PC synthesis and proinflammatory cytokine production. Results LPS-NO subgroup had the lowest level of labeled PC in total phospholipids and disaturated PC in bronchoalveolar lavage fluid and lung tissue (decreased by 46–59%), along with the lowest activity of cytidine triphosphate: phosphocholine cytidylyltransferase (-14–18%) in the lungs, compared to all other subgroups at 4 h (p < 0.01), but not at 8 and 12 h. After 24-h, all LPS-subgroups had lower labeled PC than the corresponding C-subgroups (p < 0.05). LPS-ONO had higher labeled PC in total phospholipids and disaturated PC, activity of cytidylyltransferase, and lower activity of nuclear transcription factor-κB and expression of proinflammatory cytokine mRNA, than that in the LPS-O subgroup (p < 0.05). Conclusion In LPS-induced lung inflammation in association with hyperoxia, depressed PC synthesis and enhanced proinflammatory cytokine production may be alleviated by iNO. NO alone only transiently suppressed the PC synthesis as a result of lower activity of cytidylyltransferase. PMID:16403237

  6. TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

    PubMed Central

    Gu, Yu-Han; Liu, Ming; Bai, Yang; Liang, Li-Ye; Wang, Huai-Liang

    2017-01-01

    Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity. PMID:28303170

  7. TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity.

    PubMed

    Wang, Yun; Gu, Yu-Han; Liu, Ming; Bai, Yang; Liang, Li-Ye; Wang, Huai-Liang

    2017-01-01

    Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.

  8. Protective Effect of Folic Acid on Oxidative DNA Damage

    PubMed Central

    Guo, Xiaojuan; Cui, Huan; Zhang, Haiyang; Guan, Xiaoju; Zhang, Zheng; Jia, Chaonan; Wu, Jia; Yang, Hui; Qiu, Wenting; Zhang, Chuanwu; Yang, Zuopeng; Chen, Zhu; Mao, Guangyun

    2015-01-01

    Abstract Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal. In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948. Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [β (95% confidence interval) = −0.88 (−1.62, −0.14) and P = 0.020 for low-FA; and β (95% confidence interval) = −2.68 (−3.42, −1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend

  9. Oxidative damage and redox in Lysosomal Storage Disorders: Biochemical markers.

    PubMed

    Donida, Bruna; Jacques, Carlos Eduardo Diaz; Mescka, Caroline Paula; Rodrigues, Daiane Grigolo Bardemaker; Marchetti, Desirèe Padilha; Ribas, Graziela; Giugliani, Roberto; Vargas, Carmen Regla

    2017-03-01

    Lysosomal Storage Disorders (LSD) comprise a heterogeneous group of >50 genetic disorders caused by mutations in genes that encode lysosomal enzymes, transport proteins or other gene products essential for a functional lysosomal system. As a result, abnormal accumulation of substrates within the lysosome leads to a progressive cellular impairment and dysfunction of numerous organs and systems. The exact mechanisms underlying the pathophysiology of LSD remain obscure. Previous studies proposed a relationship between oxidative stress and the pathogenesis of several inborn errors of metabolism, including LSD. Considering these points, in this paper it was reviewed oxidative stress and emerging antioxidant therapy in LSD, emphasizing studies with biological samples from patients affected by this group of conditions. These studies allow presuming that metabolites accumulated in LSD cause an increase of lysosomes' number and size, which may induce excessive production of reactive species and/or deplete the tissue antioxidant capacity, leading to damage in biomolecules. In vitro and in vivo evidence showed that cell oxidative process occurs in LSD and probably contributes to the pathophysiology of these disorders. In this context, it is possible to suggest that, in the future, antioxidants could come to be used as adjuvant therapy for LSD patients.

  10. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice.

    PubMed

    Palacino, James J; Sagi, Dijana; Goldberg, Matthew S; Krauss, Stefan; Motz, Claudia; Wacker, Maik; Klose, Joachim; Shen, Jie

    2004-04-30

    Loss-of-function mutations in parkin are the predominant cause of familial Parkinson's disease. We previously reported that parkin-/- mice exhibit nigrostriatal deficits in the absence of nigral degeneration. Parkin has been shown to function as an E3 ubiquitin ligase. Loss of parkin function, therefore, has been hypothesized to cause nigral degeneration via an aberrant accumulation of its substrates. Here we employed a proteomic approach to determine whether loss of parkin function results in alterations in abundance and/or modification of proteins in the ventral midbrain of parkin-/- mice. Two-dimensional gel electrophoresis followed by mass spectrometry revealed decreased abundance of a number of proteins involved in mitochondrial function or oxidative stress. Consistent with reductions in several subunits of complexes I and IV, functional assays showed reductions in respiratory capacity of striatal mitochondria isolated from parkin-/- mice. Electron microscopic analysis revealed no gross morphological abnormalities in striatal mitochondria of parkin-/- mice. In addition, parkin-/- mice showed a delayed rate of weight gain, suggesting broader metabolic abnormalities. Accompanying these deficits in mitochondrial function, parkin-/- mice also exhibited decreased levels of proteins involved in protection from oxidative stress. Consistent with these findings, parkin-/- mice showed decreased serum antioxidant capacity and increased protein and lipid peroxidation. The combination of proteomic, genetic, and physiological analyses reveal an essential role for parkin in the regulation of mitochondrial function and provide the first direct evidence of mitochondrial dysfunction and oxidative damage in the absence of nigral degeneration in a genetic mouse model of Parkinson's disease.

  11. Evaluation of Oxidation Damage in Thermal Barrier Coating Systems

    NASA Technical Reports Server (NTRS)

    Zhu, Dongming; Miller, Robert A.

    1996-01-01

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

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

    PubMed

    Cobley, James N; Margaritelis, Nikos V; Morton, James P; Close, Graeme L; Nikolaidis, Michalis G; Malone, John K

    2015-01-01

    Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1) redox signaling and (2) macromolecule damage. Mechanistic knowledge of how exercise-induced redox signaling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signaling 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 signaling and damage. Indeed, H2O2 can participate in two electron signaling 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 signaling 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 signaling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

  13. Oxidative damage induced in Vicia faba by coke plant wastewater.

    PubMed

    Liu, Yuxiang; Lv, Yongkang

    2011-10-01

    The present study investigated toxic impacts of coke plant wastewater over a concentration gradient of COD( Cr) 40-640 mg/l on malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in roots and leaves of Vicia faba. MDA levels and SOD activities were significantly increased at all concentrations both in roots and leaves of Vicia faba; CAT and POD activities were significantly enhanced in roots at low concentrations and were significantly decreased at high concentrations (COD(Cr) 320 and 640 mg/l for CAT; COD( Cr) 640 mg/l for POD). In leaves, CAT and POD activities remained enhanced at all concentration and did not show significant difference at COD( Cr) 640 mg/l for CAT and COD(Cr) 40, 640 mg/l for POD. These results suggest that coke plant wastewater can cause oxidative damage in roots and leaves of Vicia faba and root enzymes seemed more sensitive to the wastewater.

  14. Oxidative damage of the male reproductive system induced by paraquat.

    PubMed

    Chen, Qing; Zhang, Xin; Zhao, Jin-Yan; Lu, Xiao-Ning; Zheng, Peng-Sheng; Xue, Xiang

    2016-10-20

    The effects of paraquat (PQ) on the male reproductive system are unclear. In this study, male rats were divided into four groups (0, 0.5, 2, and 8 mg/kg) and treated with PQ by oral gavage for 8 weeks. At the end of the experiment, a significant decline in sperm count, motility, and viability and an increase in teratospermia were observed in the PQ-treated group (P < 0.05). Further investigation found that PQ resulted in enhanced lipid peroxidation and more apoptosis in the testis tissues, and apoptosis was likely to be associated with activation of the mitochondrial pathway. In summary, our study demonstrated oxidative damage due to PQ on the male reproductive system.

  15. Oxidatively induced DNA damage and its repair in cancer.

    PubMed

    Dizdaroglu, Miral

    2015-01-01

    Oxidatively induced DNA damage is caused in living organisms by endogenous and exogenous reactive species. DNA lesions resulting from this type of damage are mutagenic and cytotoxic and, if not repaired, can cause genetic instability that may lead to disease processes including carcinogenesis. Living organisms possess DNA repair mechanisms that include a variety of pathways to repair multiple DNA lesions. Mutations and polymorphisms also occur in DNA repair genes adversely affecting DNA repair systems. Cancer tissues overexpress DNA repair proteins and thus develop greater DNA repair capacity than normal tissues. Increased DNA repair in tumors that removes DNA lesions before they become toxic is a major mechanism for development of resistance to therapy, affecting patient survival. Accumulated evidence suggests that DNA repair capacity may be a predictive biomarker for patient response to therapy. Thus, knowledge of DNA protein expressions in normal and cancerous tissues may help predict and guide development of treatments and yield the best therapeutic response. DNA repair proteins constitute targets for inhibitors to overcome the resistance of tumors to therapy. Inhibitors of DNA repair for combination therapy or as single agents for monotherapy may help selectively kill tumors, potentially leading to personalized therapy. Numerous inhibitors have been developed and are being tested in clinical trials. The efficacy of some inhibitors in therapy has been demonstrated in patients. Further development of inhibitors of DNA repair proteins is globally underway to help eradicate cancer.

  16. Oxidative damage to rat brain in iron and copper overloads.

    PubMed

    Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Semprine, Jimena; Fuda, Julián; Torti, Horacio; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

  17. Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative DNA damage

    PubMed Central

    Zhang, Chao; Luo, Tao; Cui, Shijun; Gu, Yongquan; Bian, Chunjing; Chen, Yibin; Yu, Xiaochun; Wang, Zhonggao

    2015-01-01

    Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a widespread cardiovascular disease. Recent studies suggest that oxidative damage occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage. Further analysis showed that oxidative damage repair in VSMCs is suppressed by a low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational modification in oxidative damage repair. The low level of PARylation is not caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase, PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs than that in the control cells. Using PARG inhibitor to suppress PARG activity facilitates oxidative damage-induced PARylation as well as DNA damage repair. Thus, our study demonstrates a novel molecular mechanism for oxidative damage-induced VSMCs death. This study also identifies the use of PARG inhibitors as a potential treatment for atherosclerosis. [BMB Reports 2015; 48(6): 354-359] PMID:25748172

  18. Selenium and sulfur influence ethylene formation and alleviate cadmium-induced oxidative stress by improving proline and glutathione production in wheat.

    PubMed

    Khan, M Iqbal R; Nazir, Faroza; Asgher, Mohd; Per, Tasir S; Khan, Nafees A

    2015-01-15

    We have studied the influence of selenium (Se) and sulfur (S) in the protection of photosynthetic capacity of wheat (Triticum aestivum) against cadmium (Cd) stress. The involvement of ethylene and its interaction with proline and antioxidant metabolism in the tolerance of plants to Cd stress was evaluated. Application of Se or S alleviated Cd-induced oxidative stress by increasing proline accumulation as a result of increased activity of glutamyl kinase (GK) and decreased activity of proline oxidase (PROX). These nutrients also induced the activity of ATP-sulfurylase and serine acetyl transferase and the content of cysteine (Cys), a precursor for the synthesis of both reduced glutathione (GSH) and ethylene. Further, application of Se and S to plants under Cd stress reduced ethylene level and increased the activity of glutathione reductase (GR) and glutathione peroxidase (GPX), reduced oxidative stress and improved photosynthesis and growth. The involvement of ethylene in Se and S-mediated alleviation of Cd stress was substantiated with the use of ethylene biosynthesis inhibitor aminoethoxyvinylglycine (AVG). The use of AVG reversed the effects of Se and S on ethylene, content of proline and GSH and photosynthesis. The results suggested that Se and S both reversed Cd-induced oxidative stress by regulating ethylene formation, proline and GSH metabolism. Thus, Se or S-induced regulatory interaction between ethylene and proline and GSH metabolism may be used for the reversal of Cd-induced oxidative stress.

  19. Exercise pre‑conditioning alleviates brain damage via excitatory amino acid transporter 2 and extracellular signal‑regulated kinase 1/2 following ischemic stroke in rats.

    PubMed

    Wang, Xiao; Zhang, Min; Feng, Rui; Li, Wen-Bin; Ren, Shi-Qing; Zhang, Feng

    2015-02-01

    Previous studies have reported that physical exercise may exert a neuroprotective effect in humans as well as animals. However, the detailed mechanisms underlying the neuroprotective effect of exercise has remained to be elucidated. The aim of the present study was to explore the possible signaling pathways involved in the protective effect of pre‑ischemic treadmill training for ischemic stroke in rats. A total of 36 male Sprague‑Dawley rats were divided at random into three groups as follows (n=12 for each): Sham surgery group; middle cerebral artery occlusion (MCAO) group; and exercise with MCAO group. Following treadmill training for three weeks, the middle cerebral artery was occluded for 90 min in order to induce ischemic stroke, followed by reperfusion. Following 24 h post‑reperfusion, six rats from each group were assessed for neurological deficits and then sacrificed to calculate the infarct volume. The remaining rats (n=6 for each group) were sacrificed and the expression levels of excitatory amino acid transporter 2 (EAAT‑2) and extracellular signal‑regulated kinase 1/2 (ERK1/2) were detected using western blot analysis. The results of the present study demonstrated that rats that underwent pre‑ischemic exercise intervention had a significantly decreased brain infarct volume and neurological deficits; in addition, the pre‑ischemic exercise group showed decreased overexpression of phosphorylated ERK1/2 and increased expression of EAAT‑2 following ischemic stroke. In conclusion, treadmill training exercise prior to ischemic stroke alleviated brain damage in rats via regulation of EAAT‑2 and ERK1/2.

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

    PubMed Central

    Li, Y.; Ma, Q. G.; Zhao, L. H.; Guo, Y. Q.; Duan, G. X.; Zhang, J. Y.; Ji, C.

    2014-01-01

    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. PMID:25050030

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

    PubMed Central

    Luna, Carlos; Alique, Matilde; Navalmoral, Estefanía; Noci, Maria-Victoria; Bohorquez-Magro, Lourdes; Carracedo, Julia; Ramírez, Rafael

    2016-01-01

    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. PMID:27042026

  2. Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets

    PubMed Central

    Zheng, Pengfei; Xie, Zhonglin; Yuan, Yuan; Sui, Wen; Wang, Chao; Gao, Xing; Zhao, Yuanlin; Zhang, Feng; Gu, Yu; Hu, Peizhen; Ye, Jing; Feng, Xuyang; Zhang, Lijun

    2017-01-01

    Myocardial ischaemia-reperfusion (I/R) injury is a complex pathophysiological process. Current research has suggested that energy metabolism disorders, of which the abnormal consumption of fatty acids is closely related, compose the main pathological basis for myocardial I/R injury. Lipid droplets (LD) are critical regulators of lipid metabolism by LD-associated proteins. Among the lipid droplet proteins, the perilipin family members regulate lipolysis and lipogenesis through different mechanisms. Plin5, an important perilipin protein, promotes LD generation and lowers fatty acid oxidation, thus protecting the myocardium from lipotoxicity. This study investigated the protective effects of Plin5 in I/R myocardium. Our results indicated that Plin5 deficiency exacerbated the myocardial infarct area, aggravated left ventricular systolic dysfunction, reduced lipid storage, and elevated free fatty acids. Plin5-deficient myocardium exhibited severely damaged mitochondria, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. Furthermore, the decreased phosphorylation of PI3K/Akt in Plin5-null cardiomyocytes might contribute to I/R injury aggravation. In conclusion, Plin5, a new regulator of myocardial lipid metabolism, decreases free fatty acid peroxidation by inhibiting the lipolysis of intracellular lipid droplets, thus providing cardioprotection against I/R injury and shedding new light on therapeutic solutions for I/R diseases. PMID:28218306

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

    PubMed

    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.

  4. Haem oxygenase-1 is involved in salicylic acid-induced alleviation of oxidative stress due to cadmium stress in Medicago sativa.

    PubMed

    Cui, Weiti; Li, Le; Gao, Zhaozhou; Wu, Honghong; Xie, Yanjie; Shen, Wenbiao

    2012-09-01

    This work examines the involvement of haem oxygenase-1 (HO-1) in salicylic acid (SA)-induced alleviation of oxidative stress as a result of cadmium (Cd) stress in alfalfa (Medicago sativa L.) seedling roots. CdCl(2) exposure caused severe growth inhibition and Cd accumulation, which were potentiated by pre-treatment with zinc protoporphyrin (ZnPPIX), a potent HO-1 inhibitor. Pre-treatment of plants with the HO-1 inducer haemin or SA, both of which could induce MsHO1 gene expression, significantly reduced the inhibition of growth and Cd accumulation. The alleviation effects were also evidenced by a decreased content of thiobarbituric acid-reactive substances (TBARS). The antioxidant behaviour was confirmed by histochemical staining for the detection of lipid peroxidation and the loss of plasma membrane integrity. Furthermore, haemin and SA pre-treatment modulated the activities of ascorbate peroxidase (APX), superoxide dismutase (SOD), and guaiacol peroxidase (POD), or their corresponding transcripts. Significant enhancement of the ratios of reduced/oxidized homoglutathione (hGSH), ascorbic acid (ASA)/dehydroascorbate (DHA), and NAD(P)H/NAD(P)(+), and expression of their metabolism genes was observed, consistent with a decreased reactive oxygen species (ROS) distribution in the root tips. These effects are specific for HO-1, since ZnPPIX blocked the above actions, and the aggravated effects triggered by SA plus ZnPPIX were differentially reversed when carbon monoxide (CO) or bilirubin (BR), two catalytic by-products of HO-1, was added. Together, the results suggest that HO-1 is involved in the SA-induced alleviation of Cd-triggered oxidative stress by re-establishing redox homeostasis.

  5. Iron-Mediated Lysosomal Membrane Permeabilization in Ethanol-Induced Hepatic Oxidative Damage and Apoptosis: Protective Effects of Quercetin.

    PubMed

    Li, Yanyan; Chen, Man; Xu, Yanyan; Yu, Xiao; Xiong, Ting; Du, Min; Sun, Jian; Liu, Liegang; Tang, Yuhan; Yao, Ping

    2016-01-01

    Iron, in its free ferrous states, can catalyze Fenton reaction to produce OH∙, which is recognized as a crucial role in the pathogenesis of alcoholic liver diseases (ALD). As a result of continuous decomposition of iron-containing compounds, lysosomes contain a pool of redox-active iron. To investigate the important role of intralysosomal iron in alcoholic liver injury and the potential protection of quercetin, male C57BL/6J mice fed by Lieber De Carli diets containing ethanol (30% of total calories) were cotreated by quercetin or deferoxamine (DFO) for 15 weeks and ethanol-incubated mice primary hepatocytes were pretreated with FeCl3, DFO, and bafilomycin A1 at their optimal concentrations and exposure times. Chronic ethanol consumption caused an evident increase in lysosomal redox-active iron accompanying sustained oxidative damage. Iron-mediated ROS could trigger lysosomal membrane permeabilization (LMP) and subsequent mitochondria apoptosis. The hepatotoxicity was attenuated by reducing lysosomal iron while being exacerbated by escalating lysosomal iron. Quercetin substantially alleviated the alcoholic liver oxidative damage and apoptosis by decreasing lysosome iron and ameliorating iron-mediated LMP, which provided a new prospective of the use of quercetin against ALD.

  6. An Update on Oxidative Damage to Spermatozoa and Oocytes

    PubMed Central

    Opuwari, Chinyerum S.; Henkel, Ralf R.

    2016-01-01

    On the one hand, reactive oxygen species (ROS) are mandatory mediators for essential cellular functions including the function of germ cells (oocytes and spermatozoa) and thereby the fertilization process. However, the exposure of these cells to excessive levels of oxidative stress by too high levels of ROS or too low levels of antioxidative protection will render these cells dysfunctional thereby failing the fertilization process and causing couples to be infertile. Numerous causes are responsible for the delicate bodily redox system being out of balance and causing disease and infertility. Many of these causes are modifiable such as lifestyle factors like obesity, poor nutrition, heat stress, smoking, or alcohol abuse. Possible correctable measures include foremost lifestyle changes, but also supplementation with antioxidants to scavenge excessive ROS. However, this should only be done after careful examination of the patient and establishment of the individual bodily antioxidant needs. In addition, other corrective measures include sperm separation for assisted reproductive techniques. However, these techniques have to be carried out very carefully as they, if applied wrongly, bear risks of generating ROS damaging the germ cells and preventing fertilization. PMID:26942204

  7. Biological oxidative damage by carbon nanotubes: fingerprint or footprint?

    PubMed

    Hsieh, Shu-Feng; Bello, Dhimiter; Schmidt, Daniel F; Pal, Anoop K; Rogers, Eugene J

    2012-02-01

    Carbon nanotubes (CNTs) have received much attention for performance and toxicity, but vary substantially in terms of impurity type and content, morphology, and surface activity. This study determined the decrease of antioxidant capacity, defined as biological oxidative damage (BOD), of CNTs-exposed serum. The variability in several physicochemical properties of CNTs and their links to BOD elicited in human serum were explored. Tremendous variation in transition metal type and content (104-fold), specific surface area (SSA, nine-fold), and BOD were observed. Mass specific BOD (mBOD) varied from 0.006-0.187 μmol TEU mg(-1), whereas surface area specific BOD (sBOD) varied from 0.068-0.42 μmol TEU m(-2). The sBOD increased in a stepwise fashion from ∼0.1-0.32 μmol TEU m(-2) for tubes with outer diameter less than 10 nm. The mBOD and sBOD may be useful denominators of surface activity and impurity content and assist in designing safer CNTs.

  8. Transgenic Mouse Model for Reducing Oxidative Damage in Bone

    NASA Technical Reports Server (NTRS)

    Schreurs, A.-S.; Torres, S.; Truong, T.; Kumar, A.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

    2014-01-01

    Exposure to musculoskeletal disuse and radiation result in bone loss; we hypothesized that these catabolic treatments cause excess reactive oxygen species (ROS), and thereby alter the tight balance between bone resorption by osteoclasts and bone formation by osteoblasts, culminating in bone loss. To test this, we used transgenic mice which over-express the human gene for catalase, targeted to mitochondria (MCAT). Catalase is an anti-oxidant that converts the ROS hydrogen peroxide into water and oxygen. MCAT mice were shown previously to display reduced mitochondrial oxidative stress and radiosensitivity of the CNS compared to wild type controls (WT). As expected, MCAT mice expressed the transgene in skeletal tissue, and in marrow-derived osteoblasts and osteoclast precursors cultured ex vivo, and also showed greater catalase activity compared to wildtype (WT) mice (3-6 fold). Colony expansion in marrow cells cultured under osteoblastogenic conditions was 2-fold greater in the MCAT mice compared to WT mice, while the extent of mineralization was unaffected. MCAT mice had slightly longer tibiae than WT mice (2%, P less than 0.01), although cortical bone area was slightly lower in MCAT mice than WT mice (10%, p=0.09). To challenge the skeletal system, mice were treated by exposure to combined disuse (2 wk Hindlimb Unloading) and total body irradiation Cs(137) (2 Gy, 0.8 Gy/min), then bone parameters were analyzed by 2-factor ANOVA to detect possible interaction effects. Treatment caused a 2-fold increase (p=0.015) in malondialdehyde levels of bone tissue (ELISA) in WT mice, but had no effect in MCAT mice. These findings indicate that the transgene conferred protection from oxidative damage caused by treatment. Unexpected differences between WT and MCAT mice emerged in skeletal responses to treatment.. In WT mice, treatment did not alter osteoblastogenesis, cortical bone area, moment of inertia, or bone perimeter, whereas in MCAT mice, treatment increased these

  9. Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile.

    PubMed

    Kamendulis, L M; Jiang, J; Xu, Y; Klaunig, J E

    1999-08-01

    Chronic treatment of rats with acrylonitrile (ACN) resulted in a dose-related increase in glial cell tumors (astrocytomas). While the exact mechanism(s) for ACN-induced carcinogenicity remains unresolved, non-genotoxic and possibly tumor promotion modes of action appear to be involved in the induction of glial tumors. Recent studies have shown that ACN induced oxidative stress selectively in rat brain in a dose-responsive manner. The present study examined the ability of ACN to induce oxidative stress in a rat glial cell line, a target tissue, and in cultured rat hepatocytes, a non-target tissue of ACN carcinogenicity. Glial cells and hepatocytes were treated for 1, 4 and 24 h with sublethal concentrations of ACN. ACN induced an increase in oxidative DNA damage, as evidenced by increased production of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in glial cells but not in rat hepatocytes. Hydroxyl radical formation following ACN treatment was also selectively increased in glial cells. Following 1 and 4 h of ACN exposure, the levels of the non-enzymatic antioxidant glutathione, as well as the activities of the enzymatic antioxidants catalase and superoxide dismutase were significantly decreased in the rat glial cells. Lipid peroxidation and the activity of glutathione peroxidase were not affected by ACN treatment in rat glial cells. No changes in any of these biomarkers of oxidative stress were observed in hepatocytes treated with ACN. These data indicate that ACN selectively induced oxidative stress in rat glial cells.

  10. Priming of seeds with nitric oxide donor sodium nitroprusside (SNP) alleviates the inhibition on wheat seed germination by salt stress.

    PubMed

    Duan, Pei; Ding, Feng; Wang, Fang; Wang, Bao-Shan

    2007-06-01

    The effect of SNP, an NO donor, on seed germination of wheat (Triticum aestivum L. cv. 'DK961') under salt stress was studied. The results showed that priming of seeds with 0.06 mmol/L SNP for 24 h markedly alleviated the decrease of the germination percentage, germination index, vigor index and imbibition rate of wheat seeds under salt stress. SNP significantly alleviated the decrease of the beta-amylase activity but almost did not affect the alpha-amylase activity of wheat seeds under salt stress. SNP slightly increased the alpha-amylase isoenzymes (especially isoenzyme 3) and significantly increased the beta-amylase isoenzymes (especially isoenzyme d, e, f and g). SNP pretreatment decreased Na(+) content, but increased the K(+) content, resulting in a mark increase of K(+)/Na(+) ratio of wheat seedlings under salt stress. These results suggested that NO is involved in promoting wheat seed germination under salt stress by increasing the beta-amylase activity.

  11. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    PubMed

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-02-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus.

  12. Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH

    PubMed Central

    Mizrahi, Meir; Shabat, Yehudit; Ben Ya’acov, Ami; Lalazar, Gadi; Adar, Tomer; Wong, Victor; Muller, Brian; Rawlin, Grant; Ilan, Yaron

    2012-01-01

    Background Nonalcoholic steatohepatitis (NASH) is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia), containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH. Methods In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days. Results Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c) values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT) and homeostatic model assessment insulin resistance (HOMA) scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1), adiponectin and T regulatory cells. Conclusion Hyperimmune colostrum alleviates NASH. PMID:23293533

  13. Exogenous IAA differentially affects growth, oxidative stress and antioxidants system in Cd stressed Trigonella foenum-graecum L. seedlings: Toxicity alleviation by up-regulation of ascorbate-glutathione cycle.

    PubMed

    Bashri, Gausiya; Prasad, Sheo Mohan

    2016-10-01

    In the present study, effect of exogenous indole-3-acetic acid at their different levels (i.e. low; IAAL, 10µM and high; IAAH, 100µM) were studied on growth, oxidative stress biomarkers and antioxidant enzymes (SOD, POD, CAT and GST), and metabolites (AsA and GSH) as well as enzymes (APX, GR and DHAR) of ascorbate-glutathione cycle in Trigonella foenum-graecum L. seedlings grown under cadmium (Cd1, 3mgCd kg(-1) soil and Cd2, 9mgCd kg(-1) soil) stress. Cadmium (Cd) at both doses caused reduction in growth which was correlated with enhanced lipid peroxidation and damage to membrane as a result of excess accumulation of O2(•-) and H2O2. Cd also enhanced the oxidation of AsA and GSH to DHA and GSSG, respectively which give a clear sign of oxidative stress, despite of accelerated activity of enzymatic antioxidants: SOD, CAT, POD, GST as well as APX, DHAR (except in Cd2 stress) and GR. Exogenous application of IAAL resulted further rise in the activities of these enzymes, and maintained the redox status (> ratios: AsA/DHA and GSH/GSSG) of cells. The maintained redox status of cells under IAAL treatment declined the level of ROS in Cd1 and Cd2 treated seedlings thereby alleviated the Cd toxicity and this effect was more pronounced under Cd1 stress. Contrary to this, exogenous IAAH suppressed the activity of DHAR and GR and disturbed the redox status (< ratios: AsA/DHA and GSH/GSSG) of cells, hence excess accumulation of ROS further aggravated the Cd induced damage. Thus, overall results suggest that IAA at low (IAAL) and high (IAAH) doses affected the Cd toxicity differently by regulating the ascorbate-glutathione cycle as well as activity of other antioxidants in Trigonella seedlings.

  14. Polymorphic trial in oxidative damage of arsenic exposed Vietnamese

    SciTech Connect

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

    2011-10-15

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

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

    PubMed

    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.

  16. Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: The prevention of curcumin

    SciTech Connect

    Xu, Demei; Hu, Lihua; Su, Chuanyang; Xia, Xiaomin; Zhang, Pu; Fu, Juanli; Wang, Wenchao; Xu, Duo; Du, Hong; Hu, Qiuling; Song, Erqun; Song, Yang

    2014-10-15

    This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling. - Highlights: • TCBQ-intoxication significantly increased AST and ALT activities. • TCBQ-intoxication induced oxidative stress in mice liver. • TCBQ-intoxication induced inflammatory response in mice liver. • TCBQ-intoxication induced hepatotoxicity is independent of apoptosis. • Curcumin relieved TCBQ-induced liver damage remarkably.

  17. Alleviating effects of melatonin on oxidative changes in the testes and pituitary glands evoked by subacute chlorpyrifos administration in Wistar rats

    PubMed Central

    Umosen, Angela J; Ambali, Suleiman F; Ayo, Joseph O; Mohammed, Bisala; Uchendu, Chidiebere

    2012-01-01

    Objective To evaluate the alleviating effects of melatonin on oxidative changes in the testes and pituitary gland induced by subacute chlopyrifos (CPF) exposure in rats. Methods Forty adult male Wistar rats divided into 4 groups of 10 animals were used for the study. Group I received soya oil (2 mL/kg) while group II was administered with melatonin (0.5 mg/kg). Group III was administered CPF only (8.5 mg/kg ∼ 1/10th of the LD50) while group IV was pretreated with melatonin (0.5 mg/kg) and then exposed to CPF (8.5 mg/kg), 10 min later. The regimens were administered by gavage once daily for a period of 28 d. At the end of the exposure period, the rats were sacrificed and the testicular tissues and pituitary glands were evaluated for the malonaldehyde (MDA) concentration and activities of superoxide dismutase (SOD) and catalase (CAT). Results CPF increased MDA concentrations and reduced the activities of SOD and CAT in the testes and pituitary gland. Melatonin pretreatment reduced the testicular and pituitary MDA concentrations and improves the SOD and CAT activities. Conclusions the study showed that subacute CPF-induced oxidative stress in the testes and pituitary glands were alleviated by melatonin due to its antioxidant property. PMID:23569987

  18. Alleviating polarity-conflict at the heterointerfaces of KTaO{sub 3}/GdScO{sub 3} polar complex-oxides

    SciTech Connect

    Thompson, J.; Nichols, J.; Connell, J. G.; Seo, S. S. A.; Hwang, J.; Stemmer, S.

    2014-09-08

    We have synthesized and investigated the heterointerfaces of KTaO{sub 3} (KTO) and GdScO{sub 3} (GSO), which are both polar complex-oxides along the pseudo-cubic [001] direction. Since their layers have the same, conflicting net charges at interfaces, i.e., KO(−1)/ScO{sub 2}(−1) or TaO{sub 2}(+1)/GdO(+1), forming the heterointerface of KTO/GSO should be forbidden due to strong Coulomb repulsion, the so-called polarity conflict. However, we have discovered that atomic reconstruction occurs at the heterointerfaces between KTO thin-films and GSO substrates, which effectively alleviates the polarity conflict without destroying the hetero-epitaxy. Our result demonstrates one of the important ways to create artificial heterostructures from polar complex-oxides.

  19. Arbuscular mycorrhizae alleviate negative effects of zinc oxide nanoparticle and zinc accumulation in maize plants--A soil microcosm experiment.

    PubMed

    Wang, Fayuan; Liu, Xueqin; Shi, Zhaoyong; Tong, Ruijian; Adams, Catharine A; Shi, Xiaojun

    2016-03-01

    ZnO nanoparticles (NPs) are considered an emerging contaminant when in high concentration, and their effects on crops and soil microorganisms pose new concerns and challenges. Arbuscular mycorrhizal (AM) fungi (AMF) form mutualistic symbioses with most vascular plants, and putatively contribute to reducing nanotoxicity in plants. Here, we studied the interactions between ZnO NPs and maize plants inoculated with or without AMF in ZnO NPs-spiked soil. ZnO NPs had no significant adverse effects at 400 mg/kg, but inhibited both maize growth and AM colonization at concentrations at and above 800 mg/kg. Sufficient addition of ZnO NPs decreased plant mineral nutrient acquisition, photosynthetic pigment concentrations, and root activity. Furthermore, ZnO NPs caused Zn concentrations in plants to increase in a dose-dependent pattern. As the ZnO NPs dose increased, we also found a positive correlation with soil diethylenetriaminepentaacetic acid (DTPA)-extractable Zn. However, AM inoculation significantly alleviated the negative effects induced by ZnO NPs: inoculated-plants experienced increased growth, nutrient uptake, photosynthetic pigment content, and SOD activity in leaves. Mycorrhizal plants also exhibited decreased ROS accumulation, Zn concentrations and bioconcentration factor (BCF), and lower soil DTPA-extractable Zn concentrations at high ZnO NPs doses. Our results demonstrate that, at high contamination levels, ZnO NPs cause toxicity to AM symbiosis, but AMF help alleviate ZnO NPs-induced phytotoxicity by decreasing Zn bioavailability and accumulation, Zn partitioning to shoots, and ROS production, and by increasing mineral nutrients and antioxidant capacity. AMF may play beneficial roles in alleviating the negative effects and environmental risks posed by ZnO NPs in agroecosystems.

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

    NASA Astrophysics Data System (ADS)

    Pandey, B. N.; Lathika, K. M.; Mishra, K. P.

    2006-03-01

    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 γ-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.

  1. Oral supplements of aqueous extract of tomato seeds alleviate motor abnormality, oxidative impairments and neurotoxicity induced by rotenone in mice: relevance to Parkinson's disease.

    PubMed

    Gokul, Krishna; Muralidhara

    2014-07-01

    Although tomato seeds (an industrial by-product) are known to contain several bioactive compounds, studies describing their health effects are limited. Previously, we evidenced that aqueous extract of tomato seeds (TSE) markedly attenuated rotenone (ROT)-induced oxidative stress and neurotoxicity in Drosophila system. This study investigated the neuroprotective effect of TSE in a chronic ROT model of neurotoxicity in mice. Initially, we assessed the potential of oral supplements of TSE to modulate the levels of endogenous markers of oxidative stress in brain regions of mice. Subsequently, employing a co-exposure paradigm, the propensity of TSE (100 mg/kg bw, 3 weeks) to attenuate ROT-induced behavioral phenotype (gait abnormalities, anxiety-like state), oxidative dysfunctions and neurotoxicity was examined. We found that mice provided with TSE supplements exhibited progressive improvement in gait pattern and exploratory behavior. TSE markedly offset ROT-induced oxidative impairments, restored reduced glutathione levels, antioxidant defenses (superoxide dismutase, glutathione peroxidase) and protein carbonyls content in brain regions. Specifically, TSE effectively diminished ROT induced elevation in the activity levels of acetylcholinesterase and restored the dopamine levels in striatum. Interestingly, in mitochondria, TSE was able to restore the activity of mitochondrial complexes and redox state. Collectively, our findings in the chronic ROT model demonstrate the ability of TSE to alleviate behavioral phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity. Further studies in dopaminergic cell models are necessary to understand the precise molecular mechanism/s by which tomato seed bioactives offer significant neuroprotection.

  2. Does the oxidative stress theory of aging explain longevity differences in birds? II. Antioxidant systems and oxidative damage.

    PubMed

    Montgomery, Magdalene K; Buttemer, William A; Hulbert, A J

    2012-03-01

    The oxidative damage hypothesis of aging posits that the accumulation of oxidative damage is a determinant of an animal species' maximum lifespan potential (MLSP). Recent findings in extremely long-living mammal species such as naked mole-rats challenge this proposition. Among birds, parrots are exceptionally long-living with an average MLSP of 25 years, and with some species living more than 70 years. By contrast, quail are among the shortest living bird species, averaging about 5-fold lower MLSP than parrots. To test if parrots have correspondingly (i) superior antioxidant protection and (ii) lower levels of oxidative damage compared to similar-sized quail, we measured (i) total antioxidant capacity, uric acid and reduced glutathione (GSH) levels, as well as the activities of enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and catalase), and (ii) markers of mitochondrial DNA damage (8-OHdG), protein damage (protein carbonyls) and lipid peroxidation (lipid hydroperoxides and TBARS) in three species of long-living parrots and compared these results to corresponding measures in two species of short-living quails (average MLSP=5.5 years). All birds were fed the same diet to exclude differences in dietary antioxidant levels. Tissue antioxidants and oxidative damage were determined both 'per mg protein' and 'per g tissue'. Only glutathione peroxidase was consistently higher in tissues of the long-living parrots and suggests higher protection against the harmful effects of hydroperoxides, which might be important for parrot longevity. The levels of oxidative damage were mostly statistically indistinguishable between parrots and quails (67%), occasionally higher (25%), but rarely lower (8%) in the parrots. Despite indications of higher protection against some aspects of oxidative stress in the parrots, the pronounced longevity of parrots appears to be independent of their antioxidant mechanisms and their accumulation of oxidative damage.

  3. Involvement of oxidatively damaged DNA and repair in cancer development and aging

    PubMed Central

    Tudek, Barbara; Winczura, Alicja; Janik, Justyna; Siomek, Agnieszka; Foksinski, Marek; Oliński, Ryszard

    2010-01-01

    DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities. PMID:20589166

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

    SciTech Connect

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

    2008-02-15

    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.

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

    SciTech Connect

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

    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. Effects of montmorillonite on Pb accumulation, oxidative stress, and DNA damage in tilapia (Oreochromis niloticus) exposed to dietary Pb.

    PubMed

    Dai, Wei; Fu, Linglin; Du, Huahua; Liu, Huitao; Xu, Zirong

    2010-07-01

    In order to investigate the effects of montmorillonite (MMT) on reducing dietary lead (Pb) toxicity to tilapia (Oreochromis niloticus), 240 fish were randomly divided into four treatments denominated as follows: control treatment (fed with a basal diet), MMT treatment (fed with a basal diet added with 0.5% MMT), Pb treatment (fed with a basal diet added with 100 mg Pb per kilogram dry weight (dw)), and Pb + MMT treatment (fed with a basal diet added with 100 mg Pb per kilogram dw and 0.5% MMT). Changes in Pb accumulation, oxidative stress, and DNA damage in tilapia were measured after 60 days. DNA damage was assessed using comet assay. The results showed that MMT supplemented in diet significantly reduced Pb accumulation in kidney and blood of tilapia exposed to dietary Pb (P < 0.05). Malondialdehyde level decreased insignificantly while levels of total antioxidant capacity and glutathione (GSH), activities of glutathione peroxidase, and superoxide dismutase increased insignificantly in kidney of tilapia in Pb + MMT treatment as compared to Pb treatment (P > 0.05). Significant decreases in tail length, tail DNA, tail moment, and Olive tail moment of peripheral blood cells in Pb + MMT treatment were observed when compared with Pb treatment (P < 0.05). The results indicated that dietary MMT supplementation could alleviate dietary Pb toxicity to tilapia effectively.

  7. A Double-Blind Randomized Placebo Controlled Trial of Magnesium Oxide for Alleviation of Chronic Low Back Pain

    DTIC Science & Technology

    1999-01-01

    owner, and will save and hold harmless the Uniformed Services University of the Health Sciences from any damage which may arise from such copyright...is caused by stimulation of nerve endings usually due to tissue damage (Miller & Keane, 1983). Operational definition: A numeric rating scale will...excretion of magnesium by increasing secretion antidiuretic hormone, thyroid hormones, and corticoids . In addition to these effects, low serum magnesium

  8. AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE.

    EPA Science Inventory

    Ambient particulate matter (PM) damages biological targets through oxidative stress (OS) pathways. Several reports indicate that the brain is one of those targets. Since microglia (brain macrophage) are critical to OS-mediated neurodegeneration, their response to concentrated amb...

  9. 3,4-Dihydroxyphenylethanol alleviates early brain injury by modulating oxidative stress and Akt and nuclear factor-κB pathways in a rat model of subarachnoid hemorrhage

    PubMed Central

    FU, PENG; HU, QUAN

    2016-01-01

    3,4-Dihydroxyphenylethanol (DOPET) is a naturally occurring polyphenolic compound, present in olive oil and in the wastewater generated during olive oil processing. DOPET has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammatory effects. This study was designed to determine whether DOPET alleviates early brain injury (EBI) associated with subarachnoid hemorrhage (SAH) through suppression of oxidative stress and Akt and nuclear factor (NF)-κB pathways. Rats were randomly divided into the following groups: Sham group, SAH group, SAH + vehicle group and SAH + DOPET group. Mortality, blood-brain barrier (BBB) permeability and brain water content were assessed. Oxidative stress, Akt, NF-κB p65 and caspase-3 assays were also performed. DOPET induced a reduction in brain water content, and decreased the BBB permeability of SAH model rats. Furthermore, DOPET effectively controlled oxidative stress, NF-κB p65 and caspase-3 levels, in addition to significantly increasing Akt levels in the cortex following SAH. These results provide evidence that DOPET attenuates apoptosis in a rat SAH model through modulating oxidative stress and Akt and NF-κB signaling pathways. PMID:27168841

  10. Oxidatively generated base damage to cellular DNA by hydroxyl radical and one-electron oxidants: similarities and differences.

    PubMed

    Cadet, Jean; Wagner, J Richard

    2014-09-01

    Hydroxyl radical (OH) and one-electron oxidants that may be endogenously formed through oxidative metabolism, phagocytosis, inflammation and pathological conditions constitute the main sources of oxidatively generated damage to cellular DNA. It is worth mentioning that exposure of cells to exogenous physical agents (UV light, high intensity UV laser, ionizing radiation) and chemicals may also induce oxidatively generated damage to DNA. Emphasis is placed in this short review article on the mechanistic aspects of OH and one-electron oxidant-mediated formation of single and more complex damage (tandem lesions, intra- and interstrand cross-links, DNA-protein cross-links) in cellular DNA arising from one radical hit. This concerns DNA modifications that have been accurately measured using suitable analytical methods such as high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Evidence is provided that OH and one-electron oxidants after generating neutral radicals and base radical cations respectively may partly induce common degradation pathways. In addition, selective oxidative reactions giving rise to specific degradation products of OH and one-electron oxidation reactions that can be used as representative biomarkers of these oxidants have been identified.

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

    PubMed

    Gokay, Nevzat Selim; Yilmaz, Ibrahim; Komur, Baran; Demiroz, Ahu Senem; Gokce, Alper; Dervisoglu, Sergülen; Gokay, Banu Vural

    2016-01-01

    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.

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

    PubMed Central

    Gokay, Nevzat Selim; Yilmaz, Ibrahim; Demiroz, Ahu Senem; Gokce, Alper; Dervisoglu, Sergülen; Gokay, Banu Vural

    2016-01-01

    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. PMID:27382570

  13. Protective effects of curcumin on amyloid-β-induced neuronal oxidative damage.

    PubMed

    Huang, Han-Chang; Chang, Ping; Dai, Xue-Ling; Jiang, Zhao-Feng

    2012-07-01

    To investigate the protective effects of curcumin against amyloid-β (Aβ)-induced neuronal damage. Primary rat cortical neurons were cultured with different treatments of Aβ and curcumin. Neuronal morphologies, viability and damage were assessed. Neuronal oxidative stress was assessed, including extracellular hydrogen peroxide and intracellular reactive oxygen species. The abilities of curcumin to scavenge free radicals and to inhibit Aβ aggregation and β-sheeted formation are further assessed and discussed. Curcumin preserves cell viability, which is decreased by Aβ. The results of changed morphology, released Lactate dehydrogenases and cell viability assays indicate that curcumin protects Aβ-induced neuronal damage. Curcumin depresses Aβ-induced up-regulation of neuronal oxidative stress. The treatment sequence impacts the protective effect of curcumin on Aβ-induced neuronal damage. Curcumin shows a more protective effect on neuronal oxidative damage when curcumin was added into cultured neurons not later than Aβ, especially prior to Aβ. The abilities of curcumin to scavenge free radicals and to inhibit the formation of β-sheeted aggregation are both beneficial to depress Aβ-induced oxidative damage. Curcumin prevents neurons from Aβ-induced oxidative damage, implying the therapeutic usage for the treatment of Alzheimer's disease patients.

  14. A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY STYRENE OXIDE

    EPA Science Inventory

    A rapid and simple assay to detect DNA damage to calf thymus DNA caused by styrene oxide (SO) is reported. This assay is based on changes observed in the melting and annealing behavior of the damaged DNA. The melting annealing process was monitored using a fluorescence indicat...

  15. Metal Oxide Silicon /MOS/ transistors protected from destructive damage by wire

    NASA Technical Reports Server (NTRS)

    Deboo, G. J.; Devine, E. J.

    1966-01-01

    Loop of flexible, small diameter, nickel wire protects metal oxide silicon /MOS/ transistors from a damaging electrostatic potential. The wire is attached to a music-wire spring, slipped over the MOS transistor case, and released so the spring tensions the wire loop around all the transistor leads, shorting them together. This allows handling without danger of damage.

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

    SciTech Connect

    Frei, B. )

    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.

  17. Protective effects of oestradiol against cadmium-induced changes in blood parameters and oxidative damage in rats.

    PubMed

    Mladenović, Jelena; Ognjanović, Branka; Dorđević, Nataša; Matić, Miloš; Knežević, Veroljub; Stajn, Andraš; Saičić, Zorica

    2014-03-01

    The aim of this study was to investigate the protective effects of oestradiol (E2, 4 mg kg-1 b.w. i.p.) against cadmium-induced (Cd, 2 mg kg-1 b.w. i.p.) blood changes in rats. Cadmium induced a significant decline in haemoglobin, haematocrit, and total erythrocyte, lymphocyte, and thrombocyte count, whereas total leukocytes and granulocytes increased. A significant increase was also observed in serum cholesterol, triglycerides, glucose, AST, and ALT activities, whereas total protein and albumin levels dropped significantly. Administration of E2 in combination with Cd alleviated most of these adverse effects. In terms of oxidative stress, Cd significantly increased oxygen-free radicals (O₂ •- and H₂O₂) in neutrophils and lipid peroxidation in erythrocytes, whereas E2 treatment reversed these changes to control values. Acute Cd poisoning significantly lowered antioxidant enzyme (SOD and CAT) activity and the level of non-enzymatic antioxidants (GSH and vitamin E), while increasing in GSSG. Treatments with E2 reversed Cd-induced effects on the antioxidant defences and significantly lowered Cd-induced oxidative damage in erythrocytes. This study suggests that exogenous E2 effectively restores redox balance in rat erythrocytes and counters adverse haematological and biochemical effects of Cd poisoning. It also improves the antioxidant capacity of erythrocytes, acting in synergy with endogenous antioxidants.

  18. Hydrogen sulfide induces oxidative damage to RNA and DNA in a sulfide-tolerant marine invertebrate.

    PubMed

    Joyner-Matos, Joanna; Predmore, Benjamin L; Stein, Jenny R; Leeuwenburgh, Christiaan; Julian, David

    2010-01-01

    Hydrogen sulfide acts as an environmental toxin across a range of concentrations and as a cellular signaling molecule at very low concentrations. Despite its toxicity, many animals, including the mudflat polychaete Glycera dibranchiata, are periodically or continuously exposed to sulfide in their environment. We tested the hypothesis that a broad range of ecologically relevant sulfide concentrations induces oxidative stress and oxidative damage to RNA and DNA in G. dibranchiata. Coelomocytes exposed in vitro to sulfide (0-3 mmol L(-1) for 1 h) showed dose-dependent increases in oxidative stress (as 2',7'-dichlorofluorescein fluorescence) and superoxide production (as dihydroethidine fluorescence). Coelomocytes exposed in vitro to sulfide (up to 0.73 mmol L(-1) for 2 h) also acquired increased oxidative damage to RNA (detected as 8-oxo-7,8-dihydroguanosine) and DNA (detected as 8-oxo-7,8-dihydro-2'-deoxyguanosine). Worms exposed in vivo to sulfide (0-10 mmol L(-1) for 24 h) acquired elevated oxidative damage to RNA and DNA in both coelomocytes and body wall tissue. While the consequences of RNA and DNA oxidative damage are poorly understood, oxidatively damaged deoxyguanosine bases preferentially bind thymine, causing G-T transversions and potentially causing heritable point mutations. This suggests that sulfide can be an environmental mutagen in sulfide-tolerant invertebrates.

  19. Oxidative damage to poultry: from farm to fork.

    PubMed

    Estévez, M

    2015-06-01

    Poultry and poultry meat are particularly susceptible to oxidative reactions. Oxidation processes have been for decades the focus of animal and meat scientists owing to the negative impact of these reactions on animal growth, performance, and food quality. Lipid oxidation has been recognized a major threat to the quality of processed poultry products. The recent discoveries on the occurrence of protein oxidation in muscle foods have increased the scientific and technological interest in a topic that broadens the horizons of food biochemistry into innovative fields. Furthermore, in recent years we have witnessed a growing interest in consumers on the impact of diet and oxidation on health and aging. Hence, the general description of oxidative reactions as harmful phenomena goes beyond the actual impact on animal production and food quality and reaches the potential influence of oxidized foods on consumer health. Likewise, the current antioxidant strategies aim for the protection of the living tissues, the food systems, and a potential health benefit in the consumer upon ingestion. Along these lines, the application of phytochemicals and other microelements (Se, Cu) with antioxidant potential in the feeds or directly in the meat product are strategies of substantial significance. The present paper reviews in a concise manner the most relevant and novel aspects of the mechanisms and consequences of oxidative reactions in poultry and poultry meat, and describes current antioxidant strategies against these undesirable reactions.

  20. Oxidative Stress Induces Persistent Telomeric DNA Damage Responsible for Nuclear Morphology Change in Mammalian Cells

    PubMed Central

    Coluzzi, Elisa; Colamartino, Monica; Cozzi, Renata; Leone, Stefano; Meneghini, Carlo; O’Callaghan, Nathan; Sgura, Antonella

    2014-01-01

    One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG) and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to evaluate whether chromosome instability induced by oxidative stress is related specifically to telomeric damage. We treated human primary fibroblasts (MRC-5) in vitro with hydrogen peroxide (100 and 200 µM) for 1 hr and collected data at several time points. To evaluate the persistence of oxidative stress-induced DNA damage up to 24 hrs after treatment, we analysed telomeric and genomic oxidative damage by qPCR and a modified comet assay, respectively. The results demonstrate that the genomic damage is completely repaired, while the telomeric oxidative damage persists. The analysis of telomere length reveals a significant telomere shortening 48 hrs after treatment, leading us to hypothesise that residual telomere damage could be responsible for the telomere shortening observed. Considering the influence of telomere length modulation on genomic stability, we quantified abnormal nuclear morphologies (Nucleoplasmic Bridges, Nuclear Buds and Micronuclei) and observed an increase of chromosome instability in the same time frame as telomere shortening. At subsequent times (72 and 96 hrs), we observed a restoration of telomere length and a reduction of chromosome instability, leaving us to conjecture a correlation between telomere shortening/dysfunction and chromosome instability. We can conclude that oxidative base damage leads to abnormal nuclear morphologies and that telomere dysfunction is an important contributor to this effect. PMID:25354277

  1. [Effects of urease and nitrification inhibitors on alleviating the oxidation and leaching of soil urea's hydrolyzed product ammonium].

    PubMed

    Chen, Zhenhua; Chen, Lijun; Wu, Zhijie

    2005-02-01

    With simulation test of in-situ soil column, this paper studied the effects of urease inhibitor hydroquinone (HQ), nitrification inhibitors coated calcium carbide (ECC) and dicyandiamide (DCD),and their different combinations on the persistence, oxidation, and leaching of soil urea's hydrolyzed product ammonium. The results showed that compared with other treatments, the combination of HQ and DCD could effectively inhibit the oxidation of the ammonium, and make it as exchangeable form reserve in soil in a larger amount and a longer period. The inhibition of this oxidation not only decreased the accumulation of oxidized product NO3- in soil, but also decreased the potential of NO3- leaching, making the NO3- only leach to 5-10 cm in depth, and the leached amount significantly decreased.

  2. LOX-1, oxidant stress, mtDNA damage, autophagy, and immune response in atherosclerosis.

    PubMed

    Ding, Zufeng; Liu, Shijie; Wang, Xianwei; Dai, Yao; Khaidakov, Magomed; Romeo, Francesco; Mehta, Jawahar L

    2014-07-01

    As a major receptor for oxidized low density lipoprotein (ox-LDL), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is upregulated in many pathophysiological events, including endothelial cell dysfunction and smooth muscle cell growth, as well as monocyte migration and transformation into foam cells, which are present in atherosclerosis and myocardial ischemia. Excessive production of reactive oxygen species (ROS) increases LOX-1 expression, induces mitochondrial DNA damage, and activates autophagy. Damaged mitochondrial DNA that escapes from autophagy induces an inflammatory response. This paper reviews the potential link between LOX-1, mitochondrial DNA damage, autophagy, and immune response in atherosclerosis.

  3. Dimethoate-induced oxidative damage in erythrocytes of female adult rats: possible protective effect of vitamin E and selenium supplemented to diet.

    PubMed

    Ben Amara, Ibtissem; Soudani, Nejla; Hakim, Ahmed; Bouaziz, Hanen; Troudi, Afef; Zeghal, Khaled Mounir; Zeghal, Najiba

    2012-04-01

    Pesticide hazards have been accentuated by the sharp rise in their agricultural, industrial and domestic use. Acute exposure to pesticides can cause oxidative damage. Our study investigated the potential ability of selenium (Se) and/or vitamin E, used as nutritional supplements, to alleviate erythrocyte oxidative damage induced by dimethoate (DM), an organophosphate pesticide. Female Wistar rats were exposed to DM (0.2g/L(-1) of drinking water), DM + Se (0.5 mg/kg of diet), DM + vitamin E (100 mg/kg of diet), or DM + Se + vitamin E. Rats exposed to DM for 30 days showed an increase in malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities in their erythocytes, while Na(+),K(+)-ATPase and catalase activities, glutathione, non-protein thiol, vitamin E and vitamin C levels decreased. We also noted an increase in lactate dehydrogenase activity, marker of haemolysis and a decrease in acetylcholinesterase, the principal mode of organophosphorus action. Co-administration of Se or vitamin E to the diet of DM-treated rats ameliorated the biochemical parameters cited above. But the combined effect of Se and vitamin E was more powerful in antagonizing DM-induced oxidative stress. Therefore, our investigation revealed that both Se and vitamin E were useful elements in preventing DM-induced erythrocytes damage.

  4. Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

    DTIC Science & Technology

    2010-01-01

    and myogenic differentiation of hematopoietic progenitor cells in inflammatory myopathies . J Neuropathol Exp Neurol 2008; 67(7): 711-19. [26] Porto...following sublethal TBI. Oxidative stress, inflammatory response and calcium neurotoxicity-associated mechanisms are involved in radiation-induced...neuronal damage. Keyword: Calcium, cerebellum, inflammatory response, oxidative stress, Purkinje cell, sublethal radiation. INTRODUCTION Acute radiation

  5. The acute toxicity of iron and copper: biomolecule oxidation and oxidative damage in rat liver.

    PubMed

    Boveris, Alberto; Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Torti, Horacio; Massot, Francisco; Repetto, Marisa G

    2012-11-01

    The transition metals iron (Fe) and copper (Cu) are needed at low levels for normal health and at higher levels they become toxic for humans and animals. The acute liver toxicity of Fe and Cu was studied in Sprague Dawley male rats (200 g) that received ip 0-60 mg/kg FeCl(2) or 0-30 mg/kg CuSO(4). Dose and time-responses were determined for spontaneous in situ liver chemiluminescence, phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants. The doses linearly defined the tissue content of both metals. Liver chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with half maximal responses at contents (C(50%)) of 110 μgFe/g and 42 μgCu/g liver, and with half maximal time responses (t(1/2)) of 4h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C(50%) of 118 μg Fe/g and 45 μg Cu/g and with t(1/2) of 7h and 8h. Protein oxidation increased 1.6 times for Fe with C(50%) at 113 μg Fe/g and 1.2 times for Cu with 50 μg Cu/g and t(1/2) of 4h and 5h respectively. The accumulation of Fe and Cu in liver enhanced the rate of free radical reactions and produced oxidative damage. A similar free radical-mediated process, through the formation HO(•) and RO(•) by a Fenton-like homolytic scission of H(2)O(2) and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.

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

    PubMed

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

    2016-10-01

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

  7. Protective effects of gelam honey against oxidative damage in young and aged rats.

    PubMed

    Sahhugi, Zulaikha; Hasenan, Siti Maisarah; Jubri, Zakiah

    2014-01-01

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

  8. Oxidative damage induced by copper in mouse primary hepatocytes by single-cell analysis.

    PubMed

    Jing, Mingyang; Liu, Yang; Song, Wei; Yan, Yunxing; Yan, Wenbao; Liu, Rutao

    2016-01-01

    Copper can disturb the intracellular redox balance, induce oxidative stress, and subsequently cause irreversible damage, leading to a variety of diseases. In the present study, mouse primary hepatocytes were chosen to elucidate the in vitro oxidative damage of short-term copper exposure (10-200 μM) by single-cell analysis. We evaluated the toxicity of copper by reactive oxygen species (ROS), glutathione (GSH), and oxidative DNA damage at the single-cell level. Oxidative damage induced by copper was verified by the morphological changes, persistent elevations of excessive ROS and malondialdehyde (MDA), a decrease in GSH level, and the oxidative DNA damage. Furthermore, the average ROS generation, GSH consumption, and the indicators in DNA damage did not significantly change at relatively low concentrations (10 or 50 μM), but we can find the alterations of parameters in some single cells clearly. Emphasis on the analysis of single cells is conducive to gain a better understanding on the toxicity of copper. This study will also complement studies on the environmental risk assessment of copper pollution.

  9. Oxidative damage to the promoter region of SQSTM1/p62 is common to neurodegenerative disease

    PubMed Central

    Du, Yifeng; Wooten, Michael C; Wooten, Marie W.

    2009-01-01

    Recently we reported that declined SQSTM1/p62 expression in Alzheimer disease brain was age-correlated with oxidative damage to the p62 promoter. The objective of this study was to examine whether oxidative damage to the p62 promoter is common to DNA recovered from brain of individuals with neurodegenerative disease. Increased 8-OHdG staining was observed in brain sections from Alzheimer’s disease (AD), Parkinson disease (PD), Huntington disease (HD), Frontotemporal dementia (FTD), and Pick’s disease compared to control subjects. In parallel, the p62 promoter exhibited elevated oxidative damage in samples from various diseases compared to normal brain, and damage was negatively correlated with p62 expression in FTD samples. Oxidative damage to the p62 promoter induced by H2O2 treatment decreased its transcriptional activity. In keeping with this observation, the transcriptional activity of a Sp-1 element deletion mutant displayed reduced stimulus-induced activity. These findings reveal that oxidative damage to the p62 promoter decreased its transcriptional activity and might therefore account for decreased expression of p62. Altogether these results suggest that pharmacological means to increase p62 expression may be beneficial in delaying the onset of neurodegeneration. PMID:19481605

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

    PubMed

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

    2017-03-01

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

  11. Pre-fledgling oxidative damage predicts recruitment in a long-lived bird

    PubMed Central

    Noguera, José Carlos; Kim, Sin-Yeon; Velando, Alberto

    2012-01-01

    Empirical evidence has shown that stressful conditions experienced during development may exert long-term negative effects on life-history traits. Although it has been suggested that oxidative stress has long-term effects, little is known about delayed consequences of oxidative stress experienced early in life in fitness-related traits. Here, we tested whether oxidative stress during development has long-term effects on a life-history trait directly related to fitness in three colonies of European shags Phalacrocorax aristotelis. Our results revealed that recruitment probability decreased with oxidative damage during the nestling period; oxidative damage, in turn, was related to the level of antioxidant capacity. Our results suggest a link between oxidative stress during development and survival to adulthood, a key element of population dynamics. PMID:21865247

  12. Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats.

    PubMed

    Cahova, Monika; Chrastina, Petr; Hansikova, Hana; Drahota, Zdenek; Trnovska, Jaroslava; Skop, Vojtech; Spacilova, Jana; Malinska, Hana; Oliyarnyk, Olena; Papackova, Zuzana; Palenickova, Eliska; Kazdova, Ludmila

    2015-03-01

    The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg(-1) body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.

  13. Sulfur Dioxide Enhances Endogenous Hydrogen Sulfide Accumulation and Alleviates Oxidative Stress Induced by Aluminum Stress in Germinating Wheat Seeds

    PubMed Central

    Zhu, Dong-Bo; Hu, Kang-Di; Guo, Xi-Kai; Liu, Yong; Hu, Lan-Ying; Li, Yan-Hong; Wang, Song-Hua; Zhang, Hua

    2015-01-01

    Aluminum ions are especially toxic to plants in acidic soils. Here we present evidences that SO2 protects germinating wheat grains against aluminum stress. SO2 donor (NaHSO3/Na2SO3) pretreatment at 1.2 mM reduced the accumulation of superoxide anion, hydrogen peroxide, and malondialdehyde, enhanced the activities of guaiacol peroxidase, catalase, and ascorbate peroxidase, and decreased the activity of lipoxygenase in germinating wheat grains exposed to Al stress. We also observed higher accumulation of hydrogen sulfide (H2S) in SO2-pretreated grain, suggesting the tight relation between sulfite and sulfide. Wheat grains geminated in water for 36 h were pretreated with or without 1 mM SO2 donor for 12 h prior to exposure to Al stress for 48 h and the ameliorating effects of SO2 on wheat radicles were studied. SO2 donor pretreatment reduced the content of reactive oxygen species, protected membrane integrity, and reduced Al accumulation in wheat radicles. Gene expression analysis showed that SO2 donor pretreatment decreased the expression of Al-responsive genes TaWali1, TaWali2, TaWali3, TaWali5, TaWali6, and TaALMT1 in radicles exposed to Al stress. These results suggested that SO2 could increase endogenous H2S accumulation and the antioxidant capability and decrease endogenous Al content in wheat grains to alleviate Al stress. PMID:26078810

  14. Potential of casein as a nutrient intervention to alleviate lead (Pb) acetate-mediated oxidative stress and neurotoxicity: First evidence in Drosophila melanogaster.

    PubMed

    Venkareddy, Lalith Kumar; Muralidhara

    2015-05-01

    Understanding the interaction between dietary protein deficits and neurotoxicants such as lead (Pb) is critical since oxidative stress is a common denominator under such conditions. The Drosophila system is an extensively used model to investigate the interaction between nutrients and environmental toxicants. Accordingly, we have examined the hypothesis that casein (CSN) enrichment has the propensity to attenuate Pb-associated phenotype, oxidative stress and neurotoxicity in Drosophila melanogaster. Exposure of young (2-3 d) and adult flies (10-12 d old) to Pb acetate (0-20 mM, 7 d) in the medium resulted in a concentration dependent mortality and the survivors exhibited a hyperactive phenotype. While males showed higher susceptibility to Pb among both age groups, young flies were relatively more susceptible than adults. Pb exposure (5-10 mM, 5 d) among young flies caused robust oxidative stress as evidenced by markedly elevated levels of reactive oxygen species with concomitant perturbations in the activities of antioxidant enzymes (diminished SOD and elevated thioredoxin reductase) and altered redox state. Further, Pb caused significant elevation in the activity of acetylcholinesterase and dopamine levels. In a satellite study, we assessed the modulatory effect of CSN-enriched diet (1-2%) on Pb intoxication in terms of lethality, hyperactivity, oxidative stress and neurotoxicity. CSN markedly offset Pb-induced lethality and diminished the hyperactivity response. While CSN enrichment among Pb (5 mM) treated flies caused further elevation in ROS levels and thioredoxin reductase activity, the SOD levels were restored to normalcy. Further, CSN improved the activity levels of complex I-III and restored the dopamine levels. Our data suggest that Pb-induced toxicity in the Drosophila system may be predominantly mediated through oxidative stress mechanisms and the propensity of casein-enriched diet to abrogate such responses. Hence, we propose that enrichment of diet

  15. K6PC-5, a novel sphingosine kinase 1 (SphK1) activator, alleviates dexamethasone-induced damages to osteoblasts through activating SphK1-Akt signaling.

    PubMed

    Ji, Feng; Mao, Li; Liu, Yuanyuan; Cao, Xiaojian; Xie, Yue; Wang, Shouguo; Fei, Haodong

    2015-03-13

    Long-term glucocorticoid usage is a common cause of non-traumatic femoral head osteonecrosis. Glucocorticoids (i.e. dexamethasone (Dex)) could directly induce damages to osteoblasts. In the current study, we investigated the potential activity of K6PC-5 [N-(1,3-dihydroxyisopropyl)-2-hexyl-3-oxo-decanamide], a novel sphingosine kinase 1 (SphK1) activator, against this process. Our data revealed that both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts were responsible to K6PC-5. K6PC-5 activated SphK1, increased sphingosine-1-phosphate (S1P) production and induced Akt phosphorylation in cultured osteoblasts. Functionally, K6PC-5 protected osteoblasts from Dex-induced apoptosis and necrosis. Such signaling and functional effects by K6PC-5 were prevented by the SphK1 inhibitor N,N-dimethylsphingosine (DMS), and by SphK1-siRNAs. On the other hand, exogenously-added S1P activated Akt and reduced Dex-induced osteoblast damages. LY294002 and MK-2206, two established Akt inhibitors, alleviated K6PC-5- or S1P-mediated osteoblast protection against Dex. Together, our results suggest that K6PC-5 alleviates Dex-induced osteoblast injuries through activating SphK1-Akt signaling. K6PC-5 might be further investigated in animal or clinical studies for its anti-glucocorticoids-associated osteonecrosis potential.

  16. Inclusion of Konjac Flour in the Gestation Diet Changes the Gut Microbiota, Alleviates Oxidative Stress, and Improves Insulin Sensitivity in Sows

    PubMed Central

    Tan, Chengquan; Wei, Hongkui; Ao, Jiangtao; Long, Guang

    2016-01-01

    ABSTRACT Although dietary fibers contribute to health and physiology primarily via the fermentative actions of the gut microbiota of the hosts, few studies have focused on how these interactions influence the metabolic status of sows. Here, the effects of inclusion of konjac flour (KF) in a gestation diet on oxidative stress status, insulin sensitivity, and gut microbiota were investigated to elucidate the correlation between the microbiota and metabolic changes in sows. Sows were assigned to either control or 2.2% KF dietary treatment during gestation. The gut microbiota population in sows during gestation and lactation was assessed by 16S rRNA gene sequencing. The oxidative stress parameters, homeostasis model assessment (HOMA) values, and fatty acids in the blood of sows were also assessed. Compared to the control diet group, KF significantly reduced the serum levels of reactive oxygen species (ROS) and 8-hydroxy-deoxyguanosine (8-OHdG) but increased the serum concentrations of glutathione peroxidase (GSH-Px) in sows on day 1 in lactation. Additionally, sows in the KF group had a lower HOMA insulin resistance value but a higher HOMA insulin sensitivity (HOMA-IS) value. KF induced changes in the gut microbial composition at the phylum and genus levels. The increased relative abundances of Akkermansia and Roseburia in the KF group were positively correlated with the HOMA-IS. Overall, dietary KF alleviated oxidative stress and improved insulin sensitivity of sows, and the changes in the gut microbiota in response to KF may have been correlated with the host metabolism response. IMPORTANCE To date, the effect of dietary fiber on metabolism responses and gut microbiota in sows has not been investigated. Here, KF supplementation of a gestation diet in sows was found to alleviate oxidative stress and to improve insulin sensitivity. Pyrosequencing analysis revealed that KF treatment induces changes in the gut microbiota composition at the phylum and genus levels

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

    PubMed

    Hernández, José A; López-Sánchez, Rosa C; Rendón-Ramírez, Adela

    2016-01-01

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

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

    PubMed Central

    2016-01-01

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

  19. A modified alkaline Comet assay for in vivo detection of oxidative DNA damage in Drosophila melanogaster.

    PubMed

    Shukla, A K; Pragya, P; Chowdhuri, D Kar

    2011-12-24

    Modifications to the alkaline Comet assay by using lesion-specific endonucleases, such as formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (ENDOIII, also known as Nth), can detect DNA bases with oxidative damage. This modified assay can be used to assess the genotoxic/carcinogenic potential of environmental chemicals. The goal of this study was to validate the ability of this modified assay to detect oxidative stress-induced genotoxicity in Drosophila melanogaster (Oregon R(+)). In this study, we used three well known chemical oxidative stress inducers: hydrogen peroxide (H(2)O(2)), cadmium chloride (CdCl(2)) and copper sulfate (CuSO(4)). Third instar larvae of D. melanogaster were fed various concentrations of the test chemicals (50-200μM) mixed with a standard Drosophila food for 24h. Alkaline Comet assays with and without the FPG and ENDOIII enzymes were performed with midgut cells that were isolated from the control and treated larvae. Our results show a concentration-dependent increase (p<0.05-0.001) in the migration of DNA from the treated larvae. ENDOIII treatment detected more oxidative DNA damage (specifically pyrimidine damage) in the H(2)O(2) exposed larvae compared to FPG or no enzyme treatment (buffer only). In contrast, FPG treatment detected more oxidative DNA damage (specifically purine damage) in CuSO(4) exposed larvae compared to ENDOIII. Although previously reported to be a potent genotoxic agent, CdCl(2) did not induce more oxidative DNA damage than the other test chemicals. Our results show that the modified alkaline Comet assay can be used to detect oxidative stress-induced DNA damage in D. melanogaster and thus may be applicable for in vivo genotoxic assessments of environmental chemicals.

  20. Copper(I)/ABNO-catalyzed aerobic alcohol oxidation: alleviating steric and electronic constraints of Cu/TEMPO catalyst systems.

    PubMed

    Steves, Janelle E; Stahl, Shannon S

    2013-10-23

    Cu/TEMPO catalyst systems promote efficient aerobic oxidation of sterically unhindered primary alcohols and electronically activated substrates, but they show reduced reactivity with aliphatic and secondary alcohols. Here, we report a catalyst system, consisting of ((MeO)bpy)Cu(I)(OTf) and ABNO ((MeO)bpy = 4,4'-dimethoxy-2,2'-bipyridine; ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl), that mediates aerobic oxidation of all classes of alcohols, including primary and secondary allylic, benzylic, and aliphatic alcohols with nearly equal efficiency. The catalyst exhibits broad functional group compatibility, and most reactions are complete within 1 h at room temperature using ambient air as the source of oxidant.

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. Tempol protects blood proteins and lipids against peroxynitrite-mediated oxidative damage

    PubMed Central

    Mustafa, Ayman G; Bani-Ahmad, Mohammad A; Jaradat, Ahmad Q

    2015-01-01

    Oxidative stress is characterized by excessive production of various free radicals and reactive species among which, peroxynitrite is most frequently produced in several pathological conditions. Peroxynitrite is the product of the superoxide anion reaction with nitric oxide, which is reported to take place in the intravascular compartment. Several studies have reported that peroxynitrite targets red blood cells, platelets and plasma proteins, and induces various forms of oxidative damage. This in vitro study was designed to further characterize the types of oxidative damage induced in platelets and plasma proteins by peroxynitrite. This study also determined the ability of tempol to protect blood plasma and platelets against peroxynitrite-induced oxidative damage. The ability of various concentrations of tempol (25, 50, 75, and 100 µM) to antagonize peroxynitrite-induced oxidation was evaluated by measuring the levels of protein carbonyl groups and thiobarbituric-acid-reactive substances in experimental groups. Exposure of platelets and plasma to 100 µM peroxynitrite resulted in an increased levels of carbonyl groups and lipid peroxidation (P < 0.05). Tempol significantly inhibited carbonyl group formation in plasma and platelet proteins (P < 0.05). In addition, tempol significantly reduced the levels of lipid peroxidation in both plasma and platelet samples (P < 0.05). Thus, tempol has antioxidative properties against peroxynitrite-induced oxidative damage in blood plasma and platelets. PMID:25107897

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

    SciTech Connect

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

    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.

  5. Zinc oxide nanoparticles (ZnONPs) alleviate heavy metal-induced toxicity in Leucaena leucocephala seedlings: A physiochemical analysis.

    PubMed

    Venkatachalam, P; Jayaraj, M; Manikandan, R; Geetha, N; Rene, Eldon R; Sharma, N C; Sahi, S V

    2017-01-01

    The present study describes the role of zinc oxide nanoparticles (ZnONPs) in reversing oxidative stress symptoms induced by heavy metal (Cd and Pb) exposure in Leucaena leucocephala (Lam.) de Wit. Seedling growth was significantly enhanced with the augmentation of ZnONPs following Cd and Pb exposure. Heavy metal accumulations were recorded as 1253.1 mg Cd per kg DW and 1026.8 mg Pb per kg DW for the respective treatments. Results demonstrated that ZnONPs augmentation caused an increase in photosynthetic pigment and total soluble protein contents while a significant decrease in malondialdehyde (MDA-lipid peroxidation) content in leaves. Antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX) were, in turn, elevated in heavy metal-exposed leaves amended with ZnONPs. The ameliorating effect of ZnO nanoparticles on oxidative stress induced toxicity was also confirmed by the reduced MDA content and the elevated level of antioxidative enzyme activities in leaf tissues of L. leucocephala seedlings. Further, addition of ZnONPs in combination with Cd and Pb metals induced distinct genomic alterations such as presence of new DNA bands and/or absence of normal bands in the RAPD pattern of the exposed plants. This study uniquely suggests a potential role of zinc oxide nanoparticles in the remediation of heavy metal contaminated media.

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

    PubMed Central

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

    2014-01-01

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

  7. Oxidative DNA damage is a preliminary step during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

    PubMed

    Miranda, Sandra Regina; Noguti, Juliana; Carvalho, Juliana Gonçalves; Oshima, Celina Tijuko Fujiyama; Ribeiro, Daniel Araki

    2011-04-01

    The aim of this study was to investigate oxidative DNA damage during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. For this purpose, male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. The alkaline Comet assay modified with lesion-specific enzymes was used to detect single and double strand breaks, labile sites (SBs), and oxidised purines and pyrimidines. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, oxidative DNA damage was detected in the 'normal' oral epithelium. In pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks following carcinogen exposure, respectively, oxidative DNA damage was also increased (P < 0.05) when compared to negative control. In conclusion, our results suggest that oxidative DNA damage is an early event during multistep carcinogenesis assay induced by 4NQO. This kind of approach should be considered to persons with high risk of oral cancer, such as in smokers or alcohol consumers.

  8. Effects of arginine on hair damage via oxidative coloring process.

    PubMed

    Oshimura, Eiko; Ino, Masahiro

    2004-01-01

    The purpose of this study was to measure the protective effects of arginine in oxidative coloring or bleaching process. Contact angle measurement, tensile measurement and amino acid analysis were employed. As the first step, it was shown that oxidative coloring or bleaching process decreases hair surface hydrophobicity and tensile strength in wet condition. Next the study has been conducted with coloring agents in which part of the ammonia was replaced with arginine, to find that arginine reduced the oxidative change in contact angle and tensile strength. These results suggest that arginine prevents the undesirable attack by hydrogen peroxide on hair proteins and hair surface lipids. Furthermore, it is also suggested from amino acid analysis that a considerable amount of arginine is deposited on, or in hair fibers from coloring agents.

  9. The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome

    PubMed Central

    Reeg, Sandra; Jung, Tobias; Castro, José P.; Davies, Kelvin J.A.; Henze, Andrea; Grune, Tilman

    2016-01-01

    One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. PMID:27498116

  10. Smoking-promoted oxidative DNA damage response is highly correlated to lung carcinogenesis.

    PubMed

    Cao, Chao; Lai, Tianwen; Li, Miao; Zhou, Hongbin; Lv, Dan; Deng, Zaichun; Ying, Songmin; Chen, Zhihua; Li, Wen; Shen, Huahao

    2016-04-05

    Oxidative stress induced by tobacco smoking is one of the main causes of DNA damage and is known to be involved in various cancers. Smoking is the leading cause of lung cancer, while the role of cigarette smoke-induced oxidative DNA damage response during lung carcinogenesis is largely unknown. In this study, we investigated oxidative DNA damage response levels in smoking and nonsmoking patients with lung cancer, and evaluated the potential diagnostic value of 8-OHdG for lung cancer. We observed a higher level of 8-OHdG expression and secretion in airways of lung cancer patients than that of noncancer controls. 8-OHdG expression was associated with the TNM stages. Additionally, cigarette smoke-induced oxidative DNA damage response was observed in bronchial epithelial cells in vitro and in vivo. A statistical significance correlation was found between the levels of 8-OHdG and smoking index. With a cut-off value of 2.86 ng/ml, 8-OHdG showed a sensitivity and specificity of 70.0% and 73.7%, respectively, to identify a patient with lung cancer. These findings not only underscore the importance of smoking in oxidative DNA damage response of lung cancer patients, but also suggest 8-OHdG as a potential diagnostic biomarker for lung cancer.

  11. Induction of oxidative DNA damage by flavonoids of propolis: its mechanism and implication about antioxidant capacity.

    PubMed

    Tsai, Yi-Chih; Wang, Yi-Hsiang; Liou, Chih-Chiang; Lin, Yu-Cun; Huang, Haimei; Liu, Yin-Chang

    2012-01-13

    Propolis from beehives is commonly used as a home remedy for various purposes including as a topical antiseptic. Despite its antioxidant capacity, propolis induces oxidative DNA damage. In exploring the underlying mechanism, we found that the induction of oxidative DNA damage is attributed to the hydrogen peroxide (H(2)O(2)) produced by propolis. The formation of H(2)O(2) can take place without the participation of cells but requires the presence of transition metal ions such as iron. Flavonoids such as galangin, chrysin, and pinocembrin that are commonly detected in propolis have the capacity to induce oxidative DNA damage, and that capacity correlates with the production of H(2)O(2), suggesting the involvement of flavonoids in propolis in this process. On the basis of these results, we propose that the flavonoids of propolis serve as temporary carriers of electrons received from transition metal ions that are relayed to oxygen molecules to subsequently generate superoxide and H(2)O(2). In addition, propolis induces oxidative DNA damage that is subject to repair, and propolis-treated cells show a lower level of DNA damage level when challenged with another oxidative agent such as amoxicillin. This is reminiscent of an adaptive response that might contribute to the beneficial effects of propolis.

  12. Vitamin E-coated dialysis membranes reduce the levels of oxidative genetic damage in hemodialysis patients.

    PubMed

    Rodríguez-Ribera, Lara; Corredor, Zuray; Silva, Irene; Díaz, Juan Manuel; Ballarín, José; Marcos, Ricard; Pastor, Susana; Coll, Elisabet

    2017-03-01

    End-stage renal disease patients present oxidative stress status that increases when they are submitted to hemodialysis (HD). This increase in oxidative stress can affect their genetic material, among other targets. The objective of this study was to evaluate the effect of using polysulfone membranes coated with vitamin E, during the HD sessions, on the levels of genetic damage of HD patients. Forty-six patients were followed for 6 months, of whom 29 changed from conventional HD to the use of membranes coated with vitamin E. The level of genetic damage was measured using the micronucleus and the comet assays, both before and after the follow-up period. Serum vitamin E concentration was also checked. The obtained results showed that 24% of our patients presented vitamin E deficiency, and this was normalized in those patients treated with vitamin E-coated membranes. Patients with vitamin E deficiency showed higher levels of oxidative DNA damage. After the use of vitamin E-coated membranes we detected a significant decrease in the levels of oxidative damage. Additionally, hemoglobin values increased significantly with the use of vitamin E-coated membranes. In conclusion, the use of vitamin E-coated membranes supposes a decrease on the levels of oxidative DNA damage, and improves the uremic anemia status. Furthermore, the use of this type of membrane was also effective in correcting vitamin E deficiency.

  13. Oral treatment with the herbal formula B307 alleviates cardiac toxicity in doxorubicin-treated mice via suppressing oxidative stress, inflammation, and apoptosis

    PubMed Central

    Lien, Chia-Ying; Chuang, Tai-Yuan; Hsu, Chih-Hsiang; Lin, Ching-Lung; Wang, Sheue-Er; Sheu, Shuenn-Jyi; Chien, Chiang-Ting; Wu, Chung-Hsin

    2015-01-01

    Objective This study aimed to investigate whether the herbal formula B307 could alleviate doxorubicin (DOX)-induced acute cardiotoxicity. If so, we further unraveled possible molecular mechanisms of cardiac protection under treatment with the herbal formula B307. Methods Before the animal experiment, we examined relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307. To test whether oral treatment with the herbal formula B307 could alleviate cardiotoxicity, equal volumes of B307 (50 mg/kg) or saline (sham treatment) were administered to 20-week-old male mice once daily for 14 consecutive days. Then, DOX (10 mg/kg; ip) was administered to male mice under B307 and sham treatments at 22–23 weeks of age. Cardiac functions in these mice were assessed via echocardiography at 23–24 weeks of age. Then, expressions of oxidative stress, inflammation, and apoptosis-related proteins were examined in the heart tissue by immunohistochemistry and Western blotting at 24–25 weeks of age. Apart from this, mortality rate and body weight were measured during the experiment. Results In vitro, the relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307 had shown no obvious change at doses of 10–160 ng/mL. Furthermore, the relative viabilities of Huh7 cancer cells were significantly reduced under DOX treatment but showed no significant change under DOX only and DOX plus B307 treatment. In vivo, the mortality rate, body weight, and cardiac function of DOX-treated mice were obviously improved under oral treatment with the herbal formula B307. Furthermore, cardiac expressions of endothelial nitric oxide synthase, superoxide dismutase 2, and B-cell lymphoma 2 were significantly enhanced, but tumor necrosis factor alpha, NFKB1 (p50 and its precursor, p105), neurotrophin-3, Bcl-2-associated X protein, calpain, caspase 12, caspase 9, and caspase 3 were significantly suppressed in DOX-treated mice under oral treatment with

  14. Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis.

    PubMed

    Lee, Tzung-Yan; Chang, Hen-Hong; Lo, Wen-Chai; Lin, Han-Chieh

    2010-06-01

    Obesity is associated with a complex systemic inflammatory state that has been implicated in the development of hepatic steatosis. This study was to test the efficacy of Yin-Chen-Hao-Tang (YCHT), an agent that improves hepatic triglyceride metabolism in its ability to modulate pathways implicated in hepatic steatosis. Mice were fed with high-fat diet for fifteen weeks. The therapeutic mechanism of YCHT likely enhanced adiponectin and endothelial progenitor cells, and up-regulation of peroxisome proliferator-activated receptor gamma might be responsible for fatty liver diseases. In addition, YCHT anti-oxidative stress effect might be associated with inhibition of hepatic free fatty acid concentrations and elevation of the glutathione levels in hepatic tissues. Furthermore, YCHT action mechanisms might promote senescence marker protein-30 metabolism that increase resistance to hepatic oxidative stress. These findings suggest a novel therapeutic approach for fatty liver progression in obesity mice.

  15. TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation.

    PubMed

    Xiong, Jie; Wang, Kezhou; He, Jiangping; Zhang, Guangya; Zhang, Dandan; Chen, Fengling

    2016-03-18

    Autophagy flux deficiency is closely related to the development of hepatic steatosis. Transcription factor E3 (TFE3) is reported to be a crucial gene that regulates autophagy flux and lysosome function. Therefore, we investigated the role of TFE3 in a cell model of hepatic steatosis. We constructed L02 hepatocyte lines that stably over-expressed or knocked down the expression of TFE3. Subsequently, the effects of TFE3 on hepatocellular lipid metabolism were determined by autophagy flux assay, lipid oil red O (ORO) staining, immunofluorescence staining, and mitochondrial β-oxidation assessment. Finally, we analyzed whether peroxisome proliferative activated receptor gamma coactivator 1α (PGC1α) was the potential target gene of TFE3 in the regulation of hepatic steatosis using a chromatin immunoprecipitation (CHIP) assay and a luciferase reporter system. We found that overexpression of TFE3 markedly alleviated hepatocellular steatosis. On the contrary, downregulation of TFE3 resulted in an aggravated steatosis. The mechanistic studies revealed that the TFE3-manipulated regulatory effects on hepatocellular steatosis are dependent on autophagy-induced lipophagy and PGC1α-mediated fatty acid β-oxidation because blocking these pathways with an Atg5 small interfering RNA (siRNA) or PGC1α siRNA dramatically blunted the TFE3-mediated regulation of steatosis. In conclusion, TFE3 gene provides a novel insight into the treatment of hepatic steatosis and other metabolic disease.

  16. Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice.

    PubMed

    Hatanaka, Takashi; Ogawa, Daisuke; Tachibana, Hiromi; Eguchi, Jun; Inoue, Tatsuyuki; Yamada, Hiroshi; Takei, Kohji; Makino, Hirofumi; Wada, Jun

    2016-08-01

    It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured. Expansion of the mesangial matrix, interstitial fibrosis, and macrophage infiltration in kidneys were evaluated by histology. Oxidative stress and apoptosis were evaluated in kidneys and cultured proximal tubular epithelial cells. Compared with nontreated mice, dapagliflozin and insulin decreased blood glucose and hemoglobin A1c levels equally. Urine volume and water intake increased significantly in the dapagliflozin-treated group compared with those in the insulin-treated group, but there were no differences in body weight or blood pressure between the two groups. Macrophage infiltration and fibrosis in renal interstitium improved significantly in the dapagliflozin group compared with the insulin group. Oxidative stress was attenuated by dapagliflozin, and suppression occurred in a dose-dependent manner. RNAi knockdown of SGLT2 resulted in reduced oxidative stress. Dapagliflozin ameliorates diabetic nephropathy by suppressing hyperglycemia-induced oxidative stress in a manner independent of hyperglycemia improvement in Akita mice. Our findings suggest that dapagliflozin may be a novel therapeutic approach for the treatment of diabetic nephropathy.

  17. Nitric Oxide Alleviated Arsenic Toxicity by Modulation of Antioxidants and Thiol Metabolism in Rice (Oryza sativa L.)

    PubMed Central

    Singh, Amit P.; Dixit, Garima; Kumar, Amit; Mishra, Seema; Singh, Pradyumna K.; Dwivedi, Sanjay; Trivedi, Prabodh K.; Chakrabarty, Debasis; Mallick, Shekhar; Pandey, Vivek; Dhankher, Om P.; Tripathi, Rudra D.

    2016-01-01

    Nitric oxide (NO) is a gaseous signaling molecule and has a profound impact on plant growth and development. It is reported to serve as pro oxidant as well as antioxidant in plant system. In the present study, we evaluated the protective role of NO against arsenate (AsV) toxicity in rice plants. AsV exposure has hampered the plant growth, reduced the chlorophyll content, and enhanced the oxidative stress, while the exogenous NO supplementation has reverted these symptoms. NO supplementation has reduced the arsenic (As) accumulation in root as well as shoot. NO supplementation to AsV exposed plants has reduced the gene expression level of OsLsi1 and OsLsi2. AsV stress significantly impacted thiol metabolism, it reduced GSH content and GSH/GSSG ratio, and enhanced the level of PCs. NO supplementation maintained the GSH/GSSG ratio and reduced the level of PCs. NO supplementation reverted AsV induced iron deficiency in shoot and had significant impact of gene expression level of various iron transporters (OsYSL2, OsFRDL1, OsIRT1, and OsIRO2). Conclusively, exogenous application of NO could be advantageous against AsV toxicity and could confer the tolerance to AsV stress in rice. PMID:26793232

  18. The Edible Marine Alga Gracilariopsis chorda Alleviates Hypoxia/Reoxygenation-Induced Oxidative Stress in Cultured Hippocampal Neurons

    PubMed Central

    Mohibbullah, Md.; Hannan, Md. Abdul; Choi, Ji-Young; Bhuiyan, Mohammad Maqueshudul Haque; Hong, Yong-Ki; Choi, Jae-Suk; Choi, In Soon; Moon, Il Soo

    2015-01-01

    Abstract Age-related neurological disorders are of growing concern among the elderly, and natural products with neuroprotective properties have been attracting increasing attention as candidates for the prevention or treatment of neurological disorders induced by oxidative stress. In an effort to explore natural resources, we collected some common marine seaweed from the Korean peninsula and Indonesia and screened them for neuroprotective activity against hypoxia/reoxygenation (H/R)-induced oxidative stress. Of the 23 seaweeds examined, the ethanol extract of Gracilariopsis chorda (GCE) provided maximum neuroprotection at an optimum concentration of 15 μg/mL, followed by Undaria pinnatifida. GCE increased cell viability after H/R, decreased the formation of reactive oxygen species (measured by 2′,7′-dichlorodihydrofluorescein diacetate [DCF-DA] staining), and inhibited the double-stranded DNA breaks (measured by H2AX immunocytochemistry), apoptosis (measured by Annexin V/propidium iodide staining), internucleosomal DNA fragmentation (measured by DNA laddering), and dissipation of mitochondrial membrane potential (measured by JC-1 staining). Using reverse-phase high-pressure liquid chromatography, we quantitated the arachidonic acid (AA) in GCE, which provides neuroprotection against H/R-induced oxidative stress. This neuroprotective effect of AA was comparable to that of GCE. These findings suggest that the neuroprotective effect of GCE against H/R-induced neuronal death is due, at least in part, to the AA content that suppresses neuronal apoptosis. PMID:26106876

  19. Neutrophil-derived ROS contribute to oxidative DNA damage induction by quartz particles.

    PubMed

    van Berlo, Damien; Wessels, Anton; Boots, Agnes W; Wilhelmi, Verena; Scherbart, Agnes M; Gerloff, Kirsten; van Schooten, Frederik J; Albrecht, Catrin; Schins, Roel P F

    2010-12-01

    The carcinogenicity of respirable quartz is considered to be driven by reactive oxygen species (ROS) generation in association with chronic inflammation. The contribution of phagocyte-derived ROS to inflammation, oxidative stress, and DNA damage responses was investigated in the lungs of C57BL/6J wild-type and p47(phox-/-) mice, 24h after pharyngeal aspiration of DQ12 quartz (100 mg/kg bw). Bone-marrow-derived neutrophils from wild-type and p47(phox-/-) mice were used for parallel in vitro investigations in coculture with A549 human alveolar epithelial cells. Quartz induced a marked neutrophil influx in both wild-type and p47(phox-/-) mouse lungs. Significant increases in mRNA expression of the oxidative stress markers HO-1 and γ-GCS were observed only in quartz-treated wild-type animals. Oxidative DNA damage in lung tissue was not affected by quartz exposure and did not differ between p47(phox-/-) and WT mice. Differences in mRNA expression of the DNA repair genes OGG1, APE-1, DNA Polβ, and XRCC1 were also absent. Quartz treatment of cocultures containing wild-type neutrophils, but not p47(phox-/-) neutrophils, caused increased oxidative DNA damage in epithelial cells. Our study demonstrates that neutrophil-derived ROS significantly contribute to pulmonary oxidative stress responses after acute quartz exposure, yet their role in the associated induction of oxidative DNA damage could be shown only in vitro.

  20. Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons.

    PubMed

    Xu, Shangcheng; Zhou, Zhou; Zhang, Lei; Yu, Zhengping; Zhang, Wei; Wang, Yuan; Wang, Xubu; Li, Maoquan; Chen, Yang; Chen, Chunhai; He, Mindi; Zhang, Guangbin; Zhong, Min

    2010-01-22

    Increasing evidence indicates that oxidative stress may be involved in the adverse effects of radiofrequency (RF) radiation on the brain. Because mitochondrial DNA (mtDNA) defects are closely associated with various nervous system diseases and mtDNA is particularly susceptible to oxidative stress, the purpose of this study was to determine whether radiofrequency radiation can cause oxidative damage to mtDNA. In this study, we exposed primary cultured cortical neurons to pulsed RF electromagnetic fields at a frequency of 1800 MHz modulated by 217 Hz at an average special absorption rate (SAR) of 2 W/kg. At 24 h after exposure, we found that RF radiation induced a significant increase in the levels of 8-hydroxyguanine (8-OHdG), a common biomarker of DNA oxidative damage, in the mitochondria of neurons. Concomitant with this finding, the copy number of mtDNA and the levels of mitochondrial RNA (mtRNA) transcripts showed an obvious reduction after RF exposure. Each of these mtDNA disturbances could be reversed by pretreatment with melatonin, which is known to be an efficient antioxidant in the brain. Together, these results suggested that 1800 MHz RF radiation could cause oxidative damage to mtDNA in primary cultured neurons. Oxidative damage to mtDNA may account for the neurotoxicity of RF radiation in the brain.

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

    PubMed Central

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

    2010-01-01

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

  2. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage.

    PubMed

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

    2010-08-01

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

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

    PubMed

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

    2016-01-01

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

  4. Oxidative damage in keratinocytes exposed to cigarette smoke and aldehydes.

    PubMed

    Avezov, Katia; Reznick, Abraham Z; Aizenbud, Dror

    2014-06-01

    Cigarette smoke (CS) is a significant environmental source of human exposure to chemically active saturated (acetaldehyde) and α,β-unsaturated aldehydes (acrolein) inducing protein carbonylation and dysfunction. The exposure of oral tissues to environmental hazards is immense, especially in smokers. The objectives of the current study were to examine the effect of aldehydes originating from CS on intracellular proteins of oral keratinocytes and to observe the antioxidant response in these cells. Intracellular protein carbonyl modification under CS, acrolein and acetaldehyde exposure in the HaCaT keratinocyte cell line, representing oral keratinocytes was examined by Western blot. Possible intracellular enzymatic dysfunction under the above conditions was examined by lactate dehydrogenase (LDH) activity assay. Oxidative stress response was investigated, by DCF (2,7-dichlorodihydrofluorescein) assay and GSH (glutathione) oxidation. Intracellular protein carbonyls increased 5.2 times after CS exposure and 2.7 times after exposure to 1 μmol of acrolein. DCF assay revealed an increase of fluorescence intensity 3.2 and 3.1 times after CS and acrolein exposure, respectively. CS caused a 72.5% decrease in intracellular GSH levels compared to controls. Activity of intracellular LDH was preserved. α,β-Unsaturated aldehydes from CS are capable of intracellular protein carbonylation and have a role in intracellular oxidative stress elevation in keratinocytes, probably due to the reduction in GSH levels.

  5. Hydroalcoholic seed extract of Coriandrum sativum (Coriander) alleviates lead-induced oxidative stress in different regions of rat brain.

    PubMed

    Velaga, Manoj Kumar; Yallapragada, Prabhakara Rao; Williams, Dale; Rajanna, Sharada; Bettaiya, Rajanna

    2014-06-01

    Lead exposure is known to cause apoptotic neurodegeneration and neurobehavioral abnormalities in developing and adult brain by impairing cognition and memory. Coriandrum sativum is an herb belonging to Umbelliferae and is reported to have a protective effect against lead toxicity. In the present investigation, an attempt has been made to evaluate the protective activity of the hydroalcoholic extract of C. sativum seed against lead-induced oxidative stress. Male Wistar strain rats (100-120 g) were divided into four groups: control group: 1,000 mg/L of sodium acetate; exposed group: 1,000 mg/L lead acetate for 4 weeks; C. sativum treated 1 (CST1) group: 250 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure; C. sativum treated 2 (CST2) group: 500 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure. After the exposure and treatment periods, rats were sacrificed by cervical dislocation, and the whole brain was immediately isolated and separated into four regions: cerebellum, hippocampus, frontal cortex, and brain stem along with the control group. After sacrifice, blood was immediately collected into heparinized vials and stored at 4 °C. In all the tissues, reactive oxygen species (ROS), lipid peroxidation products (LPP), and total protein carbonyl content (TPCC) were estimated following standard protocols. An indicator enzyme for lead toxicity namely delta-amino levulinic acid dehydratase (δ-ALAD) activity was determined in the blood. A significant (p<0.05) increase in ROS, LPP, and TPCC levels was observed in exposed rat brain regions, while δ-ALAD showed a decrease indicating lead-induced oxidative stress. Treatment with the hydroalcoholic seed extract of C. sativum resulted in a tissue-specific amelioration of oxidative stress produced by lead.

  6. An iron-based beverage, HydroFerrate fluid (MRN-100), alleviates oxidative stress in murine lymphocytes in vitro

    PubMed Central

    Ghoneum, Mamdooh; Matsuura, Motohiro; Gollapudi, Sastry

    2009-01-01

    Background Several studies have examined the correlation between iron oxidation and H2O2 degradation. The present study was carried out to examine the protective effects of MRN-100 against stress-induced apoptosis in murine splenic cells in vitro. MRN-100, or HydroFerrate fluid, is an iron-based beverage composed of bivalent and trivalent ferrates. Methods Splenic lymphocytes from mice were cultured in the presence or absence of MRN-100 for 2 hrs and were subsequently exposed to hydrogen peroxide (H2O2) at a concentration of 25 μM for 14 hrs. Percent cell death was examined by flow cytometry and trypan blue exclusion. The effect of MRN-100 on Bcl-2 and Bax protein levels was determined by Western blot. Results Results show, as expected, that culture of splenic cells with H2O2 alone results in a significant increase in cell death (apoptosis) as compared to control (CM) cells. In contrast, pre-treatment of cells with MRN-100 followed by H2O2 treatment results in significantly reduced levels of apoptosis. In addition, MRN-100 partially prevents H2O2-induced down-regulation of the anti-apoptotic molecule Bcl-2 and upregulation of the pro-apoptotic molecule Bax. Conclusion Our findings suggest that MRN-100 may offer a protective effect against oxidative stress-induced apoptosis in lymphocytes. PMID:19409106

  7. CUPRAC colorimetric and electroanalytical methods determining antioxidant activity based on prevention of oxidative DNA damage.

    PubMed

    Uzunboy, Seda; Çekiç, Sema Demirci; Eksin, Ece; Erdem, Arzum; Apak, Reşat

    2017-02-01

    An unbalanced excess of oxygen/nitrogen species (ROS/RNS) can give oxidative hazard to DNA and other biomacromolecules under oxidative stress conditions. While the 'comet' assay for measuring DNA damage is neither specific nor practical, monitoring oxidative changes on individual DNA bases and other oxidation products needs highly specialized equipment and operators. Thus, we developed a modified CUPRAC (cupric ion reducing antioxidant capacity) colorimetric method to determine the average total damage on DNA produced by Fenton oxidation, taking advantage of the fact that the degradation products of DNA but not the original macromolecule is CUPRAC-responsive. The DNA-protective effects of water-soluble antioxidants were used to devise a novel antioxidant activity assay, considered to be physiologically more realistic than those using artificial probes. Our method, based on the measurement of DNA oxidative products with CUPRAC colorimetry proved to be 2 orders-of-magnitude more sensitive than the widely used TBARS (thiobarbituric acid-reactive substances) colorimetric assay used as reference. Additionally, the DNA damage was electrochemically investigated using pencil graphite electrodes (PGEs) as DNA sensor platform in combination with differential pulse voltammetry (DPV). The interaction of the radical species with DNA in the absence/presence of antioxidants was detected according to the changes in guanine oxidation signal.

  8. Elevated oxidative damage is correlated with reduced fitness in interpopulation hybrids of a marine copepod

    PubMed Central

    Barreto, Felipe S.; Burton, Ronald S.

    2013-01-01

    Aerobic energy production occurs via the oxidative phosphorylation pathway (OXPHOS), which is critically dependent on interactions between the 13 mitochondrial DNA (mtDNA)-encoded and approximately 70 nuclear-encoded protein subunits. Disruptive mutations in any component of OXPHOS can result in impaired ATP production and exacerbated oxidative stress; in mammalian systems, such mutations are associated with ageing as well as numerous diseases. Recent studies have suggested that oxidative stress plays a role in fitness trade-offs in life-history evolution and functional ecology. Here, we show that outcrossing between populations with divergent mtDNA can exacerbate cellular oxidative stress in hybrid offspring. In the copepod Tigriopus californicus, we found that hybrids that showed evidence of fitness breakdown (low fecundity) also exhibited elevated levels of oxidative damage to DNA, whereas those with no clear breakdown did not show significantly elevated damage. The extent of oxidative stress in hybrids appears to be dependent on the degree of genetic divergence between their respective parental populations, but this pattern requires further testing using multiple crosses at different levels of divergence. Given previous evidence in T. californicus that hybridization disrupts nuclear/mitochondrial interactions and reduces hybrid fitness, our results suggest that such negative intergenomic epistasis may also increase the production of damaging cellular oxidants; consequently, mtDNA evolution may play a significant role in generating postzygotic isolating barriers among diverging populations. PMID:23902912

  9. Quercetin protects hamster spermatogenic cells from oxidative damage induced by diethylstilboestrol.

    PubMed

    Li, G; Ma, Aituan; Shi, W; Zhong, Xiuhui

    2010-10-01

    Quercetin has been reported to be an efficient antioxidant which protects chicken spermatogonial cells from oxidative damage through increasing intracellular antioxidants and decreasing lipid peroxidation. Exposure to diethylstilboestrol (DES) could cause reproductive damage in males, which is associated with oxidative stress. This study was conducted to investigate the protective effects of quercetin on DES-induced oxidative damage in cultured hamster spermatogenic cells. The cells were treated with different concentrations of DES, and their growth status was observed under inverted microscope. The viability of spermatogenic cells was detected by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT). The contents of superoxide dismutase (SOD) in supernatants and glutathione peroxidase (GSH-Px) in cells were detected with spectrophotography. The results showed that quercetin significantly inhibited the DES-induced damage on spermatogenic cells, with the exception of the low-dose group in which no significant difference was observed. The cell survival rate increased significantly in the middle- and high-dose groups. The contents of SOD and GSH-Px were significantly elevated after medication with quercetin (P < 0.01). It can be concluded that quercetin protects spermatogenic cells against DES-induced oxidative damage through increasing intracellular antioxidants and decreasing lipid peroxidation. Quercetin plays a very important role in ameliorating reproductive toxicity induced by environmental oestrogens.

  10. Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells

    PubMed Central

    Song, Eun Ah; Kim, Hyeyoung

    2016-01-01

    The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs) and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA), shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH) and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells’ molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies. PMID:27527148

  11. Age-Dependent Oxidative DNA Damage Does Not Correlate with Reduced Proliferation of Cardiomyocytes in Humans

    PubMed Central

    Li, Minghui; Liu, Jinfen; Jiang, Chuan; Zhang, Haibo; Ye, Lincai; Zheng, Jinghao

    2017-01-01

    Background Postnatal human cardiomyocyte proliferation declines rapidly with age, which has been suggested to be correlated with increases in oxidative DNA damage in mice and plays an important role in regulating cardiomyocyte proliferation. However, the relationship between oxidative DNA damage and age in humans is unclear. Methods Sixty right ventricular outflow myocardial tissue specimens were obtained from ventricular septal defect infant patients during routine congenital cardiac surgery. These specimens were divided into three groups based on age: group A (age 0–6 months), group B (age, 7–12 months), and group C (>12 months). Each tissue specimen was subjected to DNA extraction, RNA extraction, and immunofluorescence. Results Immunofluorescence and qRT-PCR analysis revealed that DNA damage markers—mitochondrial DNA copy number, oxoguanine 8, and phosphorylated ataxia telangiectasia mutated—were highest in Group B. However immunofluorescence and qRT-PCR demonstrated that two cell proliferation markers, Ki67 and cyclin D2, were decreased with age. In addition, wheat germ agglutinin-staining indicated that the average size of cardiomyocytes increased with age. Conclusions Oxidative DNA damage of cardiomyocytes was not correlated positively with age in human beings. Oxidative DNA damage is unable to fully explain the reduced proliferation of human cardiomyocytes. PMID:28099512

  12. Oxidative DNA damage induced by activation of polychlorinated biphenyls (PCBs): implications for PCB-induced oxidative stress in breast cancer.

    PubMed

    Oakley, G G; Devanaboyina, U; Robertson, L W; Gupta, R C

    1996-12-01

    We have previously reported that mono- and dichlorinated biphenyls (PCBs) can be metabolized to dihydroxy compounds and further oxidized to reactive metabolites which form adducts with nitrogen and sulfur nucleophiles including DNA [Amaro et al. (1966) Chem. Res. Toxicol. 9, 623-629; Oakley et al. (1996) Carcinogenesis 17, 109-114]. The former studies also demonstrated that during the metabolism of PCBs superoxide may be produced. We have therefore examined the abilities of PCB metabolites to induce free radical-mediated oxidative DNA damage using a newly developed, highly sensitive, 32P-postlabeling assay for 8-oxode-oxyguanosine (8-oxodG) [Devanaboyina, U., and Gupta, R. (1996) Carcinogenesis 17, 917-924]. The incubation of 3,4-dichloro-2'5'-dihydroxybiphenyl (100 microM) with calf thymus DNA (300 micrograms/microL) in the presence of the breast tissue and milk-associated enzyme, lactoperoxidase (10 mU/mL), and H2O2 (0.5 mM) resulted in a significant increase in free radical-induced DNA damage (253 8-oxodG/10(6) nucleotides) as compared to vehicle-treated DNA (118 8-oxodG/10(6) nucleotides). Substituting CuCl(2) (100 microM) for lactoperoxidase/H2O2, however, resulted in a substantial increase in 8-oxodG content (2669 8-oxodG/10(6) nucleotides). FeCl(3) was ineffective, suggesting that CuCl(2) but not FeCl(3) mediates oxidation of PCB dihydroxy metabolites, resulting in oxidative DNA damage. The addition of catalase (100 U/mL) and sodium azide (0.1 M) reduced the effect of CuCl(2) (849 and 896 8-oxodG/10(6) nucleotides, respectively), while superoxide dismutase (600 U/mL) moderately stimulated and glutathione (100 microM) substantially stimulated 8-oxodG formation (3014 and 4415 8-oxodG/10(6) nucleotides, respectively). The effect of various buffers as well as the effects of PCB structure on Cu(II)-mediated oxidative DNA damage were examined. These results demonstrate that free radicals and oxidative DNA damage are produced during oxidation of lower chlorinated

  13. Effects of drugs used in endotoxic shock on oxidative stress and organ damage markers.

    PubMed

    Yazar, Enver; Er, Ayse; Uney, Kamil; Bulbul, Aziz; Avci, Gulcan Erbil; Elmas, Muammer; Tras, Bunyamin

    2010-04-01

    The aim of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on antioxidant status and organ damage markers in experimentally-induced endotoxemia. Rats were divided into three groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The two other groups received the following drugs (simultaneously with LPS): ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 h. Oxidative stress parameters were determined by ELISA, while serum organ damage markers were measured by autoanalyser. LSP increased (p < 0.05) malondialdehyde, 13,14-dihydro-15-keto-prostaglandin F(2 alpha) and nitric oxide, while LPS reduced vitamin C. These changes were especially inhibited (p < 0.05) by ENR + FM + high-dose DEX. LPS increased organ damages markers. Cardiac and hepatic damage was not completely inhibited by any treatment, whereas renal damage was inhibited by two treatments. This study suggested that ENR + FM + high-dose DEX is most effective in the LPS-caused oxidative stress and organ damages.

  14. DJ-1 plays an important role in caffeic acid-mediated protection of the gastrointestinal mucosa against ketoprofen-induced oxidative damage.

    PubMed

    Cheng, Yu-Ting; Ho, Cheng-Ying; Jhang, Jhih-Jia; Lu, Chi-Cheng; Yen, Gow-Chin

    2014-10-01

    Ketoprofen is widely used to alleviate pain and inflammation in clinical medicine; however, this drug may cause oxidative stress and lead to gastrointestinal (GI) ulcers. We previously reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in protecting cells against reactive oxygen species, and it facilitates the prevention of ketoprofen-induced GI mucosal ulcers. Recent reports suggested that Nrf2 becomes unstable in the absence of DJ-1/PARK7, attenuating the activity of Nrf2-regulated downstream antioxidant enzymes. Thus, increasing Nrf2 translocation by DJ-1 may represent a novel means for GI protection. In vitro, caffeic acid increases the nuclear/cytosolic Nrf2 ratio and the mRNA expression of the downstream antioxidant enzymes, ϒ-glutamyl cysteine synthetase, glutathione peroxidase, glutathione reductase, and heme oxygenase-1, by activating the JNK/p38 pathway in Int-407 cells. Moreover, knockdown of DJ-1 also reversed caffeic acid-induced nuclear Nrf2 protein expression in a JNK/p38-dependent manner. Our results also indicated that treatment of Sprague-Dawley rats with caffeic acid prior to the administration of ketoprofen inhibited oxidative damage and reversed the inhibitory effects of ketoprofen on the antioxidant system and DJ-1 protein expression in the GI mucosa. Our observations suggest that DJ-1 plays an important role in caffeic acid-mediated protection against ketoprofen-induced oxidative damage in the GI mucosa.

  15. Antioxidation of Cerium Oxide Nanoparticles to Several Series of Oxidative Damage Related to Type II Diabetes Mellitus In Vitro

    PubMed Central

    Zhai, Jing-hui; Wu, Yi; Wang, Xiao-ying; Cao, Yue; Xu, Kan; Xu, Li; Guo, Yi

    2016-01-01

    Background It is well known that cerium oxide nanoparticles (CeNPs) have intense antioxidant activity. The antioxidant property of CeNPs are widely used in different areas of research, but little is known about the oxidative damage of Cu2+ associated with Type II diabetes mellitus (T2DM). Material/Methods In our research, the function of CeNPs was tested for its protection of β-cells from the damage of Cu2+ or H2O2. We detected hydroxyl radicals using terephthalic acid assay, hydrogen peroxide using Amplex Ultra Red assay, and cell viability using MTT reduction. Results We found that CeNPs can persistently inhibit Cu2+/H2O2 evoked hydroxyl radicals and hydrogen peroxide in oxidative stress of β-cells. Conclusions CeNPs will be useful in developing strategies for the prevention of T2DM. PMID:27752033

  16. DNA damage and oxidative stress induced by acetylsalicylic acid in Daphnia magna.

    PubMed

    Gómez-Oliván, Leobardo Manuel; Galar-Martínez, Marcela; Islas-Flores, Hariz; García-Medina, Sandra; SanJuan-Reyes, Nely

    2014-08-01

    Acetylsalicylic acid is a nonsteroidal anti-inflammatory widely used due to its low cost and high effectiveness. This compound has been found in water bodies worldwide and is toxic to aquatic organisms; nevertheless its capacity to induce oxidative stress in bioindicators like Daphnia magna remains unknown. This study aimed to evaluate toxicity in D. magna induced by acetylsalicylic acid in water, using oxidative stress and DNA damage biomarkers. An acute toxicity test was conducted in order to determine the median lethal concentration (48-h LC50) and the concentrations to be used in the subsequent subacute toxicity test in which the following biomarkers were evaluated: lipid peroxidation, oxidized protein content, activity of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, and level of DNA damage. Lipid peroxidation level and oxidized protein content were significantly increased (p<0.05), and antioxidant enzymes significantly altered with respect to controls; while the DNA damage were significantly increased (p<0.05) too. In conclusion, acetylsalicylic acid induces oxidative stress and DNA damage in D. magna.

  17. Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?

    PubMed Central

    Strauss, Rupert W.; Lu, Lili; Hafiz, Gulnar; Wolfson, Yulia; Shah, Syed M.; Sophie, Raafay; Mir, Tahreem A.; Scholl, Hendrik P.

    2015-01-01

    Abstract Retinitis pigmentosa (RP) is a group of diseases in which a mutation in one of the large variety of genes causes death of rod photoreceptors. After rods die, cone photoreceptors gradually die resulting in constriction of visual fields and eventual blindness in many patients. Studies in animal models of RP have demonstrated that oxidative damage is a major contributor to cone cell death. In this study, we extended those findings to patients with RP, because compared to control patients, those with RP showed significant reduction in the reduced to oxidized glutathione (GSH/GSSG) ratio in aqueous humor and a significant increase in aqueous protein carbonyl content. In contrast, there was no significant decrease in the serum GSH/GSSG ratio or increase in carbonyl content of serum proteins. These data indicate that patients with RP have ocular oxidative stress and damage in the absence of manifestations of systemic oxidative stress and/or damage indicating that demonstrations of oxidative damage-induced cone cell death in animal models of RP may translate to human RP. These observations lead to the hypothesis that potent antioxidants will promote cone survival and function in patients with RP and that the aqueous GSH/GSSG ratio and carbonyl content on proteins may provide useful biomarkers. Antioxid. Redox Signal. 23, 643–648. PMID:25820114

  18. Exercise-induced muscle damage impairs insulin signaling pathway associated with IRS-1 oxidative modification.

    PubMed

    Aoi, W; Naito, Y; Tokuda, H; Tanimura, Y; Oya-Ito, T; Yoshikawa, T

    2012-01-01

    Strenuous exercise induces delayed-onset muscle damage including oxidative damage of cellular components. Oxidative stress to muscle cells impairs glucose uptake via disturbance of insulin signaling pathway. We investigated glucose uptake and insulin signaling in relation to oxidative protein modification in muscle after acute strenuous exercise. ICR mice were divided into sedentary and exercise groups. Mice in the exercise group performed downhill running exercise at 30 m/min for 30 min. At 24 hr after exercise, metabolic performance and insulin-signaling proteins in muscle tissues were examined. In whole body indirect calorimetry, carbohydrate utilization was decreased in the exercised mice along with reduction of the respiratory exchange ratio compared to the rested control mice. Insulin-stimulated uptake of 2-deoxy-[(3)H]glucose in damaged muscle was decreased after acute exercise. Tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidyl-3-kinase/Akt signaling were impaired by exercise, leading to inhibition of the membrane translocation of glucose transporter 4. We also found that acute exercise caused 4-hydroxy-nonenal modification of IRS-1 along with elevation of oxidative stress in muscle tissue. Impairment of insulin-induced glucose uptake into damaged muscle after strenuous exercise would be related to disturbance of insulin signal transduction by oxidative modification of IRS-1.

  19. Oxidative Damage in Pea Plants Exposed to Water Deficit or Paraquat1

    PubMed Central

    Iturbe-Ormaetxe, Iñaki; Escuredo, Pedro R.; Arrese-Igor, Cesar; Becana, Manuel

    1998-01-01

    The application of a moderate water deficit (water potential of −1.3 MPa) to pea (Pisum sativum L. cv Lincoln) leaves led to a 75% inhibition of photosynthesis and to increases in zeaxanthin, malondialdehyde, oxidized proteins, and mitochondrial, cytosolic, and chloroplastic superoxide dismutase activities. Severe water deficit (−1.9 MPa) almost completely inhibited photosynthesis, decreased chlorophylls, β-carotene, neoxanthin, and lutein, and caused further conversion of violaxanthin to zeaxanthin, suggesting damage to the photosynthetic apparatus. There were consistent decreases in antioxidants and pyridine nucleotides, and accumulation of catalytic Fe, malondialdehyde, and oxidized proteins. Paraquat (PQ) treatment led to similar major decreases in photosynthesis, water content, proteins, and most antioxidants, and induced the accumulation of zeaxanthin and damaged proteins. PQ decreased markedly ascorbate, NADPH, ascorbate peroxidase, and chloroplastic Fe-superoxide dismutase activity, and caused major increases in oxidized glutathione, NAD+, NADH, and catalytic Fe. It is concluded that, in cv Lincoln, the increase in catalytic Fe and the lowering of antioxidant protection may be involved in the oxidative damage caused by severe water deficit and PQ, but not necessarily in the incipient stress induced by moderate water deficit. Results also indicate that the tolerance to water deficit in terms of oxidative damage largely depends on the legume cultivar.

  20. L-Theanine alleviates the neuropathological changes induced by PCB (Aroclor 1254) via inhibiting upregulation of inflammatory cytokines and oxidative stress in rat brain.

    PubMed

    Sumathi, Thangarajan; Asha, Deivasigamani; Nagarajan, Ganesan; Sreenivas, Arivazhagan; Nivedha, Rajendran

    2016-03-01

    The present study is aimed at evaluating the protective role of L-theanine on aroclor 1254-induced oxidative stress in rat brain. Intraperitoneal administration of Aroclor 1254 (2 mg/kg b.wt. for 30 days) caused oxidative stress in rat brain and also caused neurobehavioral changes. Oxidative stress was assessed by determining the levels of lipid peroxide (LPO), protein carbonyl content, and changes in activities of creatine kinase (CK), acetylcholinesterase (AchE), and ATPases in the hippocampus, cerebellum and cerebral cortex of control and experimental rats. Histopathological results showed that PCB caused neuronal loss in all three regions. PCB upregulated the mRNA expressions of inflammatory cytokines. Oral administration of L-theanine (200 mg/kg b.wt.) increased the status of antioxidants, decreased the levels of LPO, nitric oxide (NO) and increased the activities of CK, AchE and ATPases. L-Theanine restored normal architecture of brain regions and downregulated the expression of inflammatory cytokines. In conclusion, L-theanine shows a protective role against PCBs-induced oxidative damage in rat brain.

  1. Astaxanthin alleviates oxidative stress insults-related derangements in human vascular endothelial cells exposed to glucose fluctuations.

    PubMed

    Abdelzaher, Lobna A; Imaizumi, Takahiro; Suzuki, Tokiko; Tomita, Kengo; Takashina, Michinori; Hattori, Yuichi

    2016-04-01

    Glycemic fluctuations may play a critical role in the pathogenesis of diabetic complications, such as cardiovascular disease. We investigated whether the oxycarotenoid astaxanthin can reduce the detrimental effects of fluctuating glucose on vascular endothelial cells. Human umbilical venous endothelial cells were incubated for 3 days in media containing 5.5mM glucose, 22 mM glucose, or 5.5mM glucose alternating with 22 mM glucose in the absence or presence of astaxanthin or N-acetyl-L-cysteine (NAC). Constant high glucose increased reactive oxygen species (ROS) generation, but such an effect was more pronounced in fluctuating glucose. This was associated with up-regulated p22(phox) expression and down-regulated peroxisome proliferator activated receptor-γ coactivator (PGC-1α) expression. Astaxanthin inhibited ROS generation, p22(phox) up-regulation, and PGC-1α down-regulation by the stimuli of glucose fluctuation. Fluctuating glucose, but not constant high glucose, significantly decreased the endothelial nitric oxide synthase (eNOS) phosphorylation level at Ser-1177 without affecting total eNOS expression, which was prevented by astaxanthin as well as by the anti-oxidant NAC. Transferase-mediated dUTP nick end labeling (TUNEL) showed increased cell apoptosis in fluctuating glucose. Glucose fluctuation also resulted in up-regulating gene expression of pro-inflammatory mediators, interleukin-6 and intercellular adhesion molecule-1. These adverse changes were subdued by astaxanthin. The phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 were significantly increased by glucose fluctuations, and astaxanthin significantly inhibited the increase in JNK and p38 phosphorylation. Taken together, our results suggest that astaxanthin can protect vascular endothelial cells against glucose fluctuation by reducing ROS generation.

  2. Coconut Haustorium Maintains Cardiac Integrity and Alleviates Oxidative Stress in Rats Subjected to Isoproterenol-induced Myocardial Infarction

    PubMed Central

    Chikku, A. M.; Rajamohan, T.

    2012-01-01

    The present study evaluates the effect of aqueous extract of coconut haustorium on isoproterenol-induced myocardial infarction in Sprague Dawley rats. Rats were pretreated with aqueous extract of coconut haustorium (40 mg/100 g) orally for 45 days. After pretreatment, myocardial infarction was induced by injecting isoproterenol subcutaneously (20 mg/100 g body weight) twice at an interval of 24 h. Activity of marker enzymes like lactate dehydrogenase, creatinine kinase-MB, aspartate transaminase and alanine transaminase were increased in the serum and decreased in the heart of isoproterenol treated rats indicating cardiac damage. These changes were significantly reduced in haustorium pretreated rats. Moreover, an increase in the activities of antioxidant enzymes and decrease in the levels of peroxidation products were observed in the myocardium of coconut haustorium pretreated rats. Histopathology of the heart of these rats showed almost normal tissue morphology. From these results, it is clear that aqueous extract of coconut haustorium possess significant cardioprotective and antioxidant properties during isoproterenol-induced myocardial infarction in rats. PMID:23716867

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

    PubMed Central

    Areti, Aparna; Yerra, Veera Ganesh; Naidu, VGM; Kumar, Ashutosh

    2014-01-01

    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. PMID:24494204

  4. Urea-induced oxidative damage in Elodea densa leaves.

    PubMed

    Maleva, Maria; Borisova, Galina; Chukina, Nadezda; Prasad, M N V

    2015-09-01

    Urea being a fertilizer is expected to be less toxic to plants. However, it was found that urea at 100 mg L(-1) caused the oxidative stress in Elodea leaves due to the formation of reactive oxygen species (ROS) and lipid peroxidation that are known to stimulate antioxidant pathway. Urea at a concentration of 500 and 1000 mg L(-1) decreased low-molecular-weight antioxidants. In this case, the antioxidant status of plants was supported by the activity of antioxidant enzymes such as superoxide dismutase and guaiacol peroxidase. A significant increase in the soluble proteins and -SH groups was observed with high concentrations of urea (30-60 % of control). Thus, the increased activity of antioxidant enzymes, low-molecular-weight antioxidants, and induced soluble protein thiols are implicated in plant resistance to oxidative stress imposed by urea. We found that guaiacol peroxidase plays an important role in the removal of the peroxide in Elodea leaves exposed to 1000 mg L(-1)of urea.

  5. Oxidative DNA Damage Response in Helicobacter pylori-Infected Mongolian Gerbils.

    PubMed

    Bae, Minkyung; Lim, Joo Weon; Kim, Hyeyoung

    2013-09-01

    Helicobacter pylori (H. pylori) induced DNA damage which may be related to gastric cancer development. The DNA damage response coordinates DNA repair, cell-cycle transition, and apoptosis through activation of DNA damage response molecules. The damaged DNA is repaired through non-homologous end joining (NHEJ) or homologous recombination (HR). In the present study, we investigated the changes of HR DNA repair proteins (ataxia-telangiectasia-mutated; ATM, ATM and Rad3-related; ATR), NHEJ repair proteins (Ku70/80), cell cycle regulators (Chk1, Chk2), and apoptosis marker (p53/p-p53) were determined in H. pylori-infected Mongolian gerbils. In addition, the effect of an antioxidant N-acetylcysteine (NAC) on H. pylori-induced DNA damage response was determined to assess the involvement of oxidative stress on DNA damage of the animals infected with H. pylori. One week after intragastric inoculation with H. pylori, Mongolian gerbils were fed with basal diet with or without 3% NAC for 6 weeks. After 6 week, the expression levels of DNA repair proteins (Ku70/80, ATM, ATR), cell cycle regulators (Chk1, Chk2) and apoptosis marker (p-p53/p53) were increased in gastric mucosa of Mongolian gerbils, which was suppressed by NAC treatment. In conclusion, oxidative stress mediates H. pylori-induced DNA damage response including NHEJ and HR repairing processes, cell cycle arrest and apoptosis in gastric mucosa of Mongolian gerbils.

  6. Modulatory effects of Moringa oleifera extracts against hydrogen peroxide-induced cytotoxicity and oxidative damage.

    PubMed

    Sreelatha, S; Padma, P R

    2011-09-01

    Studies have demonstrated that the induction of oxidative stress may be involved in oxidative DNA damage. The present study examined and assessed the hydrogen peroxide (H(2)O(2))-mediated DNA damage in human tumor KB cells and also assessed the ability of Moringa oleifera leaf extracts to inhibit the oxidative damage. H(2)O(2) imposed a stress on the membrane lipids which was quantified by the extent of thiobarbituric acid reactive substances (TBARS) formed. The leaf extracts caused a very significant inhibition of the extent of LPO formation and enhanced the activity of antioxidative enzymes such as superoxide dismutase (SOD) and catalase (CAT) in KB cells. The comet assay was employed to study the DNA damage and its inhibition by the leaf extracts. H(2)O(2) caused a significant increase in the number of cells bearing comets, resulting in significant DNA damage. The leaf extracts significantly reduced the incidence of comets in the oxidant stressed cells. The extent of cytotoxicity of H(2)O(2) in the presence and the absence of leaf extracts studied in KB tumor cells by the MTT assay showed that H(2)O(2) caused a marked decrease in the viability of KB cells where as the leaf extracts effectively increased the viability of assaulted KB cells. The observed cytoprotective activity is probably due to the antioxidant properties of its constituents, mainly phenolics. Total phenolics showed higher correlation with antioxidant activity. The leaf extracts showed higher antioxidant activity than the reference compound. These results suggest that the inhibition by the leaf extracts on oxidative DNA damage could be attributed to their free radical scavenging activities and the effect evidenced in KB cells can be in part correlated to a modulation of redox-sensitive mechanisms.

  7. Oxidative damage to macromolecules in human Parkinson disease and the rotenone model.

    PubMed

    Sanders, Laurie H; Greenamyre, J Timothy

    2013-09-01

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

  8. Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1.

    PubMed

    Rhee, David B; Ghosh, Avik; Lu, Jian; Bohr, Vilhelm A; Liu, Yie

    2011-01-02

    Telomeres are nucleoprotein complexes at the ends of linear chromosomes in eukaryotes, and are essential in preventing chromosome termini from being recognized as broken DNA ends. Telomere shortening has been linked to cellular senescence and human aging, with oxidative stress as a major contributing factor. 7,8-Dihydro-8-oxogaunine (8-oxodG) is one of the most abundant oxidative guanine lesions, and 8-oxoguanine DNA glycosylase (OGG1) is involved in its removal. In this study, we examined if telomeric DNA is particularly susceptible to oxidative base damage and if telomere-specific factors affect the incision of oxidized guanines by OGG1. We demonstrated that telomeric TTAGGG repeats were more prone to oxidative base damage and repaired less efficiently than non-telomeric TG repeats in vivo. We also showed that the 8-oxodG-incision activity of OGG1 is similar in telomeric and non-telomeric double-stranded substrates. In addition, telomere repeat binding factors TRF1 and TRF2 do not impair OGG1 incision activity. Yet, 8-oxodG in some telomere structures (e.g., fork-opening, 3'-overhang, and D-loop) were less effectively excised by OGG1, depending upon its position in these substrates. Collectively, our data indicate that the sequence context of telomere repeats and certain telomere configurations may contribute to telomere vulnerability to oxidative DNA damage processing.

  9. FNDC5 Alleviates Hepatosteatosis by Restoring AMPK/mTOR-Mediated Autophagy, Fatty Acid Oxidation, and Lipogenesis in Mice.

    PubMed

    Liu, Tong-Yan; Xiong, Xiao-Qing; Ren, Xing-Sheng; Zhao, Ming-Xia; Shi, Chang-Xiang; Wang, Jue-Jin; Zhou, Ye-Bo; Zhang, Feng; Han, Ying; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-11-01

    Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of subcutaneous fat and mediates the beneficial effects of exercise on metabolism. However, whether FNDC5 is associated with hepatic steatosis, autophagy, fatty acid oxidation (FAO), and lipogenesis remains unknown. Herein, we show the roles and mechanisms of FNDC5 in hepatic steatosis, autophagy, and lipid metabolism. Fasted FNDC5(-/-) mice exhibited severe steatosis, reduced autophagy, and FAO, and enhanced lipogenesis in the liver compared with wild-type mice. Energy deprivation-induced autophagy, FAO, and AMPK activity were attenuated in FNDC5(-/-) hepatocytes, which were restored by activating AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Inhibition of mammalian target of rapamycin (mTOR) complex 1 with rapamycin enhanced autophagy and FAO and attenuated lipogenesis and steatosis in FNDC5(-/-) livers. FNDC5 deficiency exacerbated hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. Exogenous FNDC5 stimulated autophagy and FAO gene expression in hepatocytes and repaired the attenuated autophagy and palmitate-induced steatosis in FNDC5(-/-) hepatocytes. FNDC5 overexpression prevented hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. These results indicate that FNDC5 deficiency impairs autophagy and FAO and enhances lipogenesis via the AMPK/mTOR pathway. FNDC5 deficiency aggravates whereas FNDC5 overexpression prevents the HFD-induced hyperlipemia, hepatic lipid accumulation, and impaired FAO and autophagy in the liver.

  10. Alleviation of Lead Toxicity by 5-Aminolevulinic Acid Is Related to Elevated Growth, Photosynthesis, and Suppressed Ultrastructural Damages in Oilseed Rape

    PubMed Central

    Tian, Tian; Qin, Yebo; Gill, Rafaqat A.; Ali, Shafaqat

    2014-01-01

    Lead (Pb) is a widely spread pollutant and leads to diverse morphological and structural changes in the plants. In this study, alleviating role of 5-aminolevulinic acid (ALA) in oilseed rape (Brassica napus L.) was investigated with or without foliar application of ALA (25 mg L−1) in hydroponic environment under different Pb levels (0, 100, and 400 µM). Outcomes stated that plant morphology and photosynthetic attributes were reduced under the application of Pb alone. However, ALA application significantly increased the plant growth and photosynthetic parameters under Pb toxicity. Moreover, ALA also lowered the Pb concentration in shoots and roots under Pb toxicity. The microscopic studies depicted that exogenously applied ALA ameliorated the Pb stress and significantly improved the cell ultrastructures. After application of ALA under Pb stress, mesophyll cell had well-developed nucleus and chloroplast having a number of starch granules. Moreover, micrographs illustrated that root tip cell contained well-developed nucleus, a number of mitochondria, and golgi bodies. These results proposed that under 15-day Pb-induced stress, ALA improved the plant growth, chlorophyll content, photosynthetic parameters, and ultrastructural modifications in leaf mesophyll and root tip cells of the B. napus plants. PMID:24683549

  11. Alleviation of lead toxicity by 5-aminolevulinic acid is related to elevated growth, photosynthesis, and suppressed ultrastructural damages in oilseed rape.

    PubMed

    Tian, Tian; Ali, Basharat; Qin, Yebo; Malik, Zaffar; Gill, Rafaqat A; Ali, Shafaqat; Zhou, Weijun

    2014-01-01

    Lead (Pb) is a widely spread pollutant and leads to diverse morphological and structural changes in the plants. In this study, alleviating role of 5-aminolevulinic acid (ALA) in oilseed rape (Brassica napus L.) was investigated with or without foliar application of ALA (25 mg L(-1)) in hydroponic environment under different Pb levels (0, 100, and 400 µM). Outcomes stated that plant morphology and photosynthetic attributes were reduced under the application of Pb alone. However, ALA application significantly increased the plant growth and photosynthetic parameters under Pb toxicity. Moreover, ALA also lowered the Pb concentration in shoots and roots under Pb toxicity. The microscopic studies depicted that exogenously applied ALA ameliorated the Pb stress and significantly improved the cell ultrastructures. After application of ALA under Pb stress, mesophyll cell had well-developed nucleus and chloroplast having a number of starch granules. Moreover, micrographs illustrated that root tip cell contained well-developed nucleus, a number of mitochondria, and golgi bodies. These results proposed that under 15-day Pb-induced stress, ALA improved the plant growth, chlorophyll content, photosynthetic parameters, and ultrastructural modifications in leaf mesophyll and root tip cells of the B. napus plants.

  12. Mdivi-1 Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats, Possibly via Inhibition of Drp1-Activated Mitochondrial Fission and Oxidative Stress.

    PubMed

    Wu, Pei; Li, Yuchen; Zhu, Shiyi; Wang, Chunlei; Dai, Jiaxing; Zhang, Guang; Zheng, Bingjie; Xu, Shancai; Wang, Ligang; Zhang, Tongyu; Zhou, PeiQuan; Zhang, John H; Shi, Huaizhang

    2017-02-16

    Mdivi-1 is a selective inhibitor of mitochondrial fission protein, Drp1, and can penetrate the blood-brain barrier. Previous studies have shown that Mdivi-1 improves neurological outcomes after ischemia, seizures and trauma but it remains unclear whether Mdivi-1 can attenuate early brain injury after subarachnoid hemorrhage (SAH). We thus investigated the therapeutic effect of Mdivi-1 on early brain injury following SAH. Rats were randomly divided into four groups: sham; SAH; SAH + vehicle; and SAH + Mdivi-1. The SAH model was induced by standard intravascular perforation and all of the rats were subsequently sacrificed 24 h after SAH. Mdivi-1 (1.2 mg/kg) was administered to rats 30 min after SAH. We found that Mdivi-1 markedly improved neurologic deficits, alleviated brain edema and BBB permeability, and attenuated apoptotic cell death. Mdivi-1 also significantly reduced the expression of cleaved caspase-3, Drp1 and p-Drp1((Ser616)), attenuated the release of Cytochrome C from mitochondria, inhibited excessive mitochondrial fission, and restored the ultra-structure of mitochondria. Furthermore, Mdivi-1 reduced levels of MDA, 3-NT, and 8-OHdG, and improved SOD activity. Taken together, our data suggest that Mdivi-1 exerts neuroprotective effects against cell death induced by SAH and the underlying mechanism may be inhibition of Drp1-activated mitochondrial fission and oxidative stress.

  13. Protective effect of spermidine on salt stress induced oxidative damage in two Kentucky bluegrass (Poa pratensis L.) cultivars.

    PubMed

    Puyang, Xuehua; An, Mengying; Han, Liebao; Zhang, Xunzhong

    2015-07-01

    To improve the salinity tolerance of turfgrass and investigate the effect of spermidine (Spd) on antioxidant metabolism and gene expression under salinity stress condition, exogenous Spd was applied before two kentucky bluegrass (Poa pratensis L.) cultivars ('Kenblue' and 'Midnight') were exposed to 200 mM sodium chloride (NaCl) stress for 28 d. Salinity stress decreased the turfgrass quality, increased the content of malonyldialdehyde (MDA), superoxide anion (O₂(·-)) and hydrogen peroxide (H₂O₂), and enhanced activities of superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POD) and ascorbate peroxidase (APX) and isozymes intensity in both cultivars. In addition, the expression level of Cu/ZnSOD was down-regulated in 'Kenblue' but up-regulated in 'Midnight' after salt treatment. Salinity stress also enhanced the expression of APX but inhibited the expression of CAT and POD in both cultivars. Exogenous Spd treatment alleviated the salinity-induced oxidative stress through decreasing MDA, H₂O₂ and O₂(·-) contents in both cultivars. Besides, exogenous Spd further enhanced the activities of SOD, CAT, POD and APX accompanied with the increased intensity of specific isozymes of SOD, CAT and APX in both cultivars and POD in 'Kenblue'. Moreover, Spd further up-regulated expression levels of Cu/ZnSOD and APX, but down-regulated those of CAT and POD in both cultivars. These results indicated that exogenous Spd might improve turfgrass quality and promote the salinity tolerance in the two cultivars of kentucky bluegrass through reducing oxidative damages and increasing enzyme activity both at protein and transcriptional levels.

  14. Trichosanatine alleviates oxidized low-density lipoprotein induced endothelial cells injury via inhibiting the LOX-1/p38 MAPK pathway.

    PubMed

    Zhang, Lei; Jia, Yu-Hua; Zhao, Xiao-Shan; Zhou, Feng-Hua; Pan, Yun-Yun; Wan, Qiang; Cui, Xiao-Bing; Sun, Xue-Gang; Chen, Yu-Yao; Zhang, Yu; Cheng, Sai-Bo

    2016-01-01

    The LOX-1/p38 mitogen-activated protein kinase (MAPK) pathway has been proved to participate in the endothelial dysfunction in atherosclerosis. Trichosanatineis is an active compound isolated from the peel of Trichosanthes kirilowii. This study aims to determine whether trichosanatine prevents the oxidized low-density lipoprotein (ox-LDL)-induced insult through inhibition of the LOX-1/p38 MAPK pathway in HUVECs. HUVECs were treated with 150 mg/ml ox-LDL for 24 h to establish an ox-LDL-induced endothelial injury model. Cell viability, mitochondrial membrane potential (MMP), apoptosis, reactive oxygen species (ROS) level, LOX-1 and p38 MAPK expression level were measured. The results indicated that HUVECs were pretreated with either 100 mM trichosanatine or LOX-1 shRNA prior to exposure to ox-LDL for 24 h. Exposure of HUVECs to 150 mg/ml ox-LDL for 24 h significantly up-regulated the expression levels of LOX-1. The increased expression levels of LOX-1 were markedly attenuated by pretreatment with 100 mM trichosanatine. In addition, the ox-LDL-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with LOX-1 shRNA. Pretreatment of HUVECs with either trichosanatine or LOX-1 shRNA before exposure to ox-LDL significantly inhibited the ox-LDL-induced injuries, as evidenced by an increase in cell viability, a decrease in apoptotic cells, a ROS generation and a loss of MMP. In conclusion, we have demonstrated for the first time that the LOX-1/p38 MAPK pathway contributes to the ox-LDL-induced injury in HUVECs. Meanwhile, the trichosanatine protects the HUVECs against ox-LDL-induced injury at least in part by inhibiting the activated of LOX-1/p38 MAPK pathway.

  15. Trichosanatine alleviates oxidized low-density lipoprotein induced endothelial cells injury via inhibiting the LOX-1/p38 MAPK pathway

    PubMed Central

    Zhang, Lei; Jia, Yu-Hua; Zhao, Xiao-Shan; Zhou, Feng-Hua; Pan, Yun-Yun; Wan, Qiang; Cui, Xiao-Bing; Sun, Xue-Gang; Chen, Yu-Yao; Zhang, Yu; Cheng, Sai-Bo

    2016-01-01

    The LOX-1/p38 mitogen-activated protein kinase (MAPK) pathway has been proved to participate in the endothelial dysfunction in atherosclerosis. Trichosanatineis is an active compound isolated from the peel of Trichosanthes kirilowii. This study aims to determine whether trichosanatine prevents the oxidized low-density lipoprotein (ox-LDL)-induced insult through inhibition of the LOX-1/p38 MAPK pathway in HUVECs. HUVECs were treated with 150 mg/ml ox-LDL for 24 h to establish an ox-LDL-induced endothelial injury model. Cell viability, mitochondrial membrane potential (MMP), apoptosis, reactive oxygen species (ROS) level, LOX-1 and p38 MAPK expression level were measured. The results indicated that HUVECs were pretreated with either 100 mM trichosanatine or LOX-1 shRNA prior to exposure to ox-LDL for 24 h. Exposure of HUVECs to 150 mg/ml ox-LDL for 24 h significantly up-regulated the expression levels of LOX-1. The increased expression levels of LOX-1 were markedly attenuated by pretreatment with 100 mM trichosanatine. In addition, the ox-LDL-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with LOX-1 shRNA. Pretreatment of HUVECs with either trichosanatine or LOX-1 shRNA before exposure to ox-LDL significantly inhibited the ox-LDL-induced injuries, as evidenced by an increase in cell viability, a decrease in apoptotic cells, a ROS generation and a loss of MMP. In conclusion, we have demonstrated for the first time that the LOX-1/p38 MAPK pathway contributes to the ox-LDL-induced injury in HUVECs. Meanwhile, the trichosanatine protects the HUVECs against ox-LDL-induced injury at least in part by inhibiting the activated of LOX-1/p38 MAPK pathway. PMID:28078016

  16. PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

    PubMed Central

    Choi, Yoon Jeong; Kim, Nayoung; Lee, Ju Yup; Nam, Ryoung Hee; Suh, Ji Hyung; Lee, Sun Min; Ham, Min Hee; Jo, Hyun Jin; Shim, Young Kwang; Park, Yo Han; Lee, Jong-Chan; Choi, Yoon Jin; Lee, Hye Seung; Lee, Dong Ho

    2016-01-01

    Background/Aims The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. Methods The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. Results As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. Conclusions These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach. PMID:27172930

  17. Effect of Acacia catechu (L.f.) Willd. on Oxidative Stress with Possible Implications in Alleviating Selected Cognitive Disorders

    PubMed Central

    Saha, Manas Ranjan; Dey, Priyankar; Begum, Sainiara; De, Bratati; Chaudhuri, Tapas Kr.; Sarker, Dilip De; Das, Abhaya Prasad; Sen, Arnab

    2016-01-01

    In human body, several categories of degenerative processes are largely determined by free radicals originating in cell. Free radicals are also known to have correlated with a variety of cognitive disorders (CDs) resulting in neuronal injury and eventually to death. Alzheimer’s disease (AD) and Parkinson's disease (PD) are such kind of killer CDs that occur due to dysfunction of cholinergic and dopaminergic neurons. Plant parts of Ginkgo biloba, Bacopa monnieri etc. are being used for the treatment of cognitive disorders in several countries. The present study was aimed to explore the detailed antioxidant and anti-cholinesterase activity of Acaciacatechu leaf (ACL) over CDs. Gas chromatography-Mass spectroscopy (GC-MS) analysis and Nuclear Magnetic Resonance (NMR) were employed to identify the bioactive components present in ACL. Furthermore, the extract was evaluated to check the cytotoxic effects of ACL on normal cells. Amongst several antioxidant assays, DPPH assay, hydroxyl radical, nitric oxide radical and hypochlorous acid inhibitory activities were found to be greater in ACL than that of the respective standards while other assays exhibited a moderate or at per inhibitory activity with standards. Total phenolic and flavonoid content were also found to be present in decent amount. In addition, we found, a greater acetylcholinesterase (AChE) inhibitory activity of ACL when compared to other medicinally important plants, indicating its positive effect over CDs. Forty one bioactive components were explored through GC-MS. Of these, gallic acid, epicatechin, catechin, isoquercitrin etc. were found, which are potent antioxidant and a few of them have anti-neurodegenerative properties. Eventually, ACL was found to be nontoxic and safer to consume. Further studies with animal or human model however, would determine its efficacy as a potential anti-schizophrenic drug. PMID:26949964

  18. Effect of Acacia catechu (L.f.) Willd. on Oxidative Stress with Possible Implications in Alleviating Selected Cognitive Disorders.

    PubMed

    Saha, Manas Ranjan; Dey, Priyankar; Begum, Sainiara; De, Bratati; Chaudhuri, Tapas Kr; Sarker, Dilip De; Das, Abhaya Prasad; Sen, Arnab

    2016-01-01

    In human body, several categories of degenerative processes are largely determined by free radicals originating in cell. Free radicals are also known to have correlated with a variety of cognitive disorders (CDs) resulting in neuronal injury and eventually to death. Alzheimer's disease (AD) and Parkinson's disease (PD) are such kind of killer CDs that occur due to dysfunction of cholinergic and dopaminergic neurons. Plant parts of Ginkgo biloba, Bacopa monnieri etc. are being used for the treatment of cognitive disorders in several countries. The present study was aimed to explore the detailed antioxidant and anti-cholinesterase activity of Acaciacatechu leaf (ACL) over CDs. Gas chromatography-Mass spectroscopy (GC-MS) analysis and Nuclear Magnetic Resonance (NMR) were employed to identify the bioactive components present in ACL. Furthermore, the extract was evaluated to check the cytotoxic effects of ACL on normal cells. Amongst several antioxidant assays, DPPH assay, hydroxyl radical, nitric oxide radical and hypochlorous acid inhibitory activities were found to be greater in ACL than that of the respective standards while other assays exhibited a moderate or at per inhibitory activity with standards. Total phenolic and flavonoid content were also found to be present in decent amount. In addition, we found, a greater acetylcholinesterase (AChE) inhibitory activity of ACL when compared to other medicinally important plants, indicating its positive effect over CDs. Forty one bioactive components were explored through GC-MS. Of these, gallic acid, epicatechin, catechin, isoquercitrin etc. were found, which are potent antioxidant and a few of them have anti-neurodegenerative properties. Eventually, ACL was found to be nontoxic and safer to consume. Further studies with animal or human model however, would determine its efficacy as a potential anti-schizophrenic drug.

  19. Effect of Oxidative Damage on the Stability and Dimerization of Superoxide Dismutase 1

    PubMed Central

    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 linked to both familial and sporadic amyotrophic lateral sclerosis (ALS), a devastating, late-onset motor neuronal disease, with more than 150 ALS-related mutations in the SOD1 gene. Importantly, oxidatively damaged SOD1 aggregates have been observed in both familial and sporadic forms of the disease. However, the molecular mechanisms as well as potential implications of oxidative stress in SOD1-induced cytotoxicity remain elusive. In this study, we examine the effects of oxidative modification on SOD1 monomer and homodimer stability, the key molecular properties related to SOD1 aggregation. We use molecular dynamics simulations in combination with thermodynamic integration to study microscopic-level site-specific effects of oxidative “mutations” at the dimer interface, including lysine, arginine, proline and threonine carbonylation, and cysteine oxidation. Our results show that oxidative damage of even single residues at the interface may drastically destabilize the SOD1 homodimer, with several modifications exhibiting a comparable effect to that of the most drastic ALS-causing mutations known. Additionally, we show that the SOD1 monomer stability decreases upon oxidative stress, which may lead to partial local unfolding and consequently to increased aggregation propensity. Importantly, these results suggest that oxidative stress may play a key role in development of ALS, with the mutations in the SOD1 gene being an additional factor. PMID:27074676

  20. Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: potential implications in atherosclerosis

    PubMed Central

    Karnewar, Santosh; Vasamsetti, Sathish Babu; Gopoju, Raja; Kanugula, Anantha Koteswararao; Ganji, Sai Krishna; Prabhakar, Sripadi; Rangaraj, Nandini; Tupperwar, Nitin; Kumar, Jerald Mahesh; Kotamraju, Srigiridhar

    2016-01-01

    Mitochondria-targeted compounds are emerging as a new class of drugs that can potentially alter the pathophysiology of those diseases where mitochondrial dysfunction plays a critical role. We have synthesized a novel mitochondria-targeted esculetin (Mito-Esc) with an aim to investigate its effect during oxidative stress-induced endothelial cell death and angiotensin (Ang)-II-induced atherosclerosis in ApoE−/− mice. Mito-Esc but not natural esculetin treatment significantly inhibited H2O2- and Ang-II-induced cell death in human aortic endothelial cells by enhancing NO production via AMPK-mediated eNOS phosphorylation. While L-NAME (NOS inhibitor) significantly abrogated Mito-Esc-mediated protective effects, Compound c (inhibitor of AMPK) significantly decreased Mito-Esc-mediated increase in NO production. Notably, Mito-Esc promoted mitochondrial biogenesis by enhancing SIRT3 expression through AMPK activation; and restored H2O2-induced inhibition of mitochondrial respiration. siSIRT3 treatment not only completely reversed Mito-Esc-mediated mitochondrial biogenetic marker expressions but also caused endothelial cell death. Furthermore, Mito-Esc administration to ApoE−/− mice greatly alleviated Ang-II-induced atheromatous plaque formation, monocyte infiltration and serum pro-inflammatory cytokines levels. We conclude that Mito-Esc is preferentially taken up by the mitochondria and preserves endothelial cell survival during oxidative stress by modulating NO generation via AMPK. Also, Mito-Esc-induced SIRT3 plays a pivotal role in mediating mitochondrial biogenesis and perhaps contributes to its anti-atherogenic effects. PMID:27063143

  1. Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: potential implications in atherosclerosis.

    PubMed

    Karnewar, Santosh; Vasamsetti, Sathish Babu; Gopoju, Raja; Kanugula, Anantha Koteswararao; Ganji, Sai Krishna; Prabhakar, Sripadi; Rangaraj, Nandini; Tupperwar, Nitin; Kumar, Jerald Mahesh; Kotamraju, Srigiridhar

    2016-04-11

    Mitochondria-targeted compounds are emerging as a new class of drugs that can potentially alter the pathophysiology of those diseases where mitochondrial dysfunction plays a critical role. We have synthesized a novel mitochondria-targeted esculetin (Mito-Esc) with an aim to investigate its effect during oxidative stress-induced endothelial cell death and angiotensin (Ang)-II-induced atherosclerosis in ApoE(-/-) mice. Mito-Esc but not natural esculetin treatment significantly inhibited H2O2- and Ang-II-induced cell death in human aortic endothelial cells by enhancing NO production via AMPK-mediated eNOS phosphorylation. While L-NAME (NOS inhibitor) significantly abrogated Mito-Esc-mediated protective effects, Compound c (inhibitor of AMPK) significantly decreased Mito-Esc-mediated increase in NO production. Notably, Mito-Esc promoted mitochondrial biogenesis by enhancing SIRT3 expression through AMPK activation; and restored H2O2-induced inhibition of mitochondrial respiration. siSIRT3 treatment not only completely reversed Mito-Esc-mediated mitochondrial biogenetic marker expressions but also caused endothelial cell death. Furthermore, Mito-Esc administration to ApoE(-/-) mice greatly alleviated Ang-II-induced atheromatous plaque formation, monocyte infiltration and serum pro-inflammatory cytokines levels. We conclude that Mito-Esc is preferentially taken up by the mitochondria and preserves endothelial cell survival during oxidative stress by modulating NO generation via AMPK. Also, Mito-Esc-induced SIRT3 plays a pivotal role in mediating mitochondrial biogenesis and perhaps contributes to its anti-atherogenic effects.

  2. Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Alleviates Doxorubicin-Induced Depressive-Like Behaviors and Neurotoxicity in Rats: Involvement of Oxidative Stress and Neuroinflammation.

    PubMed

    Wu, Yan-Qin; Dang, Rui-Li; Tang, Mi-Mi; Cai, Hua-Lin; Li, Huan-De; Liao, De-Hua; He, Xin; Cao, Ling-Juan; Xue, Ying; Jiang, Pei

    2016-04-23

    Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use can cause neurobiological side-effects associated with depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), the essential fatty acids found in fish oil, possess neuroprotecitve and antidepressant activities. Thus, the aim of this study was to explore the potential protective effects of ω-3 PUFAs against DOX-induced behavioral changes and neurotoxicity. ω-3 PUFAs were given daily by gavage (1.5 g/kg) over three weeks starting seven days before DOX administration (2.5 mg/kg). Open-field test (OFT) and forced swimming test (FST) were conducted to assess exploratory activity and despair behavior, respectively. Our data showed that ω-3 PUFAs supplementation significantly mitigated the behavioral changes induced by DOX. ω-3 PUFAs pretreatment also alleviated the DOX-induced neural apoptosis. Meanwhile, ω-3 PUFAs treatment ameliorated DOX-induced oxidative stress in the prefrontal cortex and hippocampus. Additionally, gene expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the protein levels of NF-κB and iNOS were significantly increased in brain tissues of DOX-treated group, whereas ω-3 PUFAs supplementation significantly attenuated DOX-induced neuroinflammation. In conclusion, ω-3 PUFAs can effectively protect against DOX-induced depressive-like behaviors, and the mechanisms underlying the neuroprotective effect are potentially associated with its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  3. Mfd is required for rapid recovery of transcription following UV-induced DNA damage but not oxidative DNA damage in Escherichia coli.

    PubMed

    Schalow, Brandy J; Courcelle, Charmain T; Courcelle, Justin

    2012-05-01

    Transcription-coupled repair (TCR) is a cellular process by which some forms of DNA damage are repaired more rapidly from transcribed strands of active genes than from nontranscribed strands or the overall genome. In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions. However, its contribution to the restoration of transcription and to global repair of oxidative damage has not been examined. Here, we report the first direct study of transcriptional recovery following UV-induced and oxidative DNA damage in E. coli. We observed that mutations in mfd or uvrA reduced the rate that transcription recovered following UV-induced damage. In contrast, no difference was detected in the rate of transcription recovery in mfd, uvrA, fpg, nth, or polB dinB umuDC mutants relative to wild-type cells following oxidative damage. mfd mutants were also fully resistant to hydrogen peroxide (H(2)O(2)) and removed oxidative lesions from the genome at rates comparable to wild-type cells. The results demonstrate that Mfd promotes the rapid recovery of gene expression following UV-induced damage in E. coli. In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.

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

    PubMed

    Vázquez-Medina, José Pablo; Crocker, Daniel E; Forman, Henry Jay; Ortiz, Rudy M

    2010-07-15

    Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences.

  5. Noninvasive prediction of prostatic DNA damage by oxidative stress challenge of peripheral blood lymphocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To move closer to the goal of individualized risk prediction for prostate cancer, we used an in vivo canine model to evaluate whether genetic instability, expressed as the susceptibility of peripheral blood lymphocytes (PBLs) to oxidative stress-induced DNA damage, could identify those individuals w...

  6. Microfluidic array for simultaneous detection of DNA oxidation and DNA-adduct damage.

    PubMed

    Song, Boya; Shen, Min; Jiang, Di; Malla, Spundana; Mosa, Islam M; Choudhary, Dharamainder; Rusling, James F

    2016-10-21

    Exposure to chemical pollutants and pharmaceuticals may cause health issues caused by metabolite-related toxicity. This paper reports a new microfluidic electrochemical sensor array with the ability to simultaneously detect common types of DNA damage including oxidation and nucleobase adduct formation. Sensors in the 8-electrode screen-printed carbon array were coated with thin films of metallopolymers osmium or ruthenium bipyridyl-poly(vinylpyridine) chloride (OsPVP, RuPVP) along with DNA and metabolic enzymes by layer-by-layer electrostatic assembly. After a reaction step in which test chemicals and other necessary reagents flow over the array, OsPVP selectively detects oxidized guanines on the DNA strands, and RuPVP detects DNA adduction by metabolites on nucleobases. We demonstrate array performance for test chemicals including 17β-estradiol (E2), its metabolites 4-hydroxyestradiol (4-OHE2), 2-hydroxyestradiol (2-OHE2), catechol, 2-nitrosotoluene (2-NO-T), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 2-acetylaminofluorene (2-AAF). Results revealed DNA-adduct and oxidation damage in a single run to provide a metabolic-genotoxic chemistry screen. The array measures damage directly in unhydrolyzed DNA, and is less expensive, faster, and simpler than conventional methods to detect DNA damage. The detection limit for oxidation is 672 8-oxodG per 10(6) bases. Each sensor requires only 22 ng of DNA, so the mass detection limit is 15 pg (∼10 pmol) 8-oxodG.

  7. Oxidative DNA damage in XPC-knockout and its wild mice treated with equine estrogen.

    PubMed

    Okamoto, Yoshinori; Chou, Pei-Hsin; Kim, Sung Yeon; Suzuki, Naomi; Laxmi, Y R Santosh; Okamoto, Kanako; Liu, Xiaoping; Matsuda, Tomonari; Shibutani, Shinya

    2008-05-01

    Long-term hormone replacement therapy with equine estrogens is associated with a higher risk of breast, ovarian, and endometrial cancers. Reactive oxygen species generated through redox cycling of equine estrogen metabolites may damage cellular DNA. Such oxidative stress may be linked to the development of cancers in reproductive organs. Xeroderma pigmentosa complementation group C-knockout ( Xpc-KO) and wild-type mice were treated with equilenin (EN), and the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) was determined as a marker of typical oxidative DNA damage, using liquid chromatography electrospray tandem mass spectrometry. The level of hepatic 8-oxodG in wild-type mice treated with EN (5 or 50 mg/kg/day) was significantly increased by approximately 220% after 1 week, as compared with mice treated with vehicle. In the uterus also, the level of 8-oxodG was significantly increased by more than 150% after 2 weeks. Similar results were observed with Xpc-KO mice, indicating that Xpc does not significantly contribute to the repair of oxidative damage. Oxidative DNA damage generated by equine estrogens may be involved in equine estrogen carcinogenesis.

  8. Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease.

    PubMed

    Najafzadeh, Mojgan; Reynolds, P Dominic; Baumgartner, Adolf; Jerwood, David; Anderson, Diana

    2007-01-01

    Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H_{2}O_{2 } dose (50 microg/ml) was used with variable doses of Chaga extract (10-500 microg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H_{2}O_{2 } induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    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.

  11. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage

    PubMed Central

    Bhattacharya, Anannya; Hegazy, Ahmed N.; Deigendesch, Nikolaus; Kosack, Lindsay; Cupovic, Jovana; Kandasamy, Richard K.; Hildebrandt, Andrea; Merkler, Doron; Kühl, Anja A.; Vilagos, Bojan; Schliehe, Christopher; Panse, Isabel; Khamina, Kseniya; Baazim, Hatoon; Arnold, Isabelle; Flatz, Lukas; Xu, Haifeng C.; Lang, Philipp A.; Aderem, Alan; Takaoka, Akinori; Superti-Furga, Giulio; Colinge, Jacques; Ludewig, Burkhard; Löhning, Max; Bergthaler, Andreas

    2015-01-01

    Summary Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1−/− mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1−/− and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. Video Abstract PMID:26588782

  12. Oxidative Damage Induced by Arsenic in Mice or Rats: A Systematic Review and Meta-Analysis.

    PubMed

    Xu, Mengchuan; Rui, Dongsheng; Yan, Yizhong; Xu, Shangzhi; Niu, Qiang; Feng, Gangling; Wang, Yan; Li, Shugang; Jing, Mingxia

    2017-03-01

    In this meta-analysis, studies reporting arsenic-induced oxidative damage in mouse models were systematically evaluated to provide a scientific understanding of oxidative stress mechanisms associated with arsenic poisoning. Fifty-eight relevant peer-reviewed publications were identified through exhaustive database searching. Oxidative stress indexes assessed included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR), oxidized glutathione (GSSG), malondialdehyde (MDA), and reactive oxygen species (ROS). Our meta-analysis showed that arsenic exposure generally suppressed measured levels of the antioxidants, SOD, CAT, GSH, GPx, GST, and GR, but increased levels of the oxidants, GSSG, MDA, and ROS. Arsenic valence was important and GR and MDA levels increased to a significantly (P < 0.05) greater extent upon exposure to As(3+) than to As(5+). Other factors that contributed to a greater overall oxidative effect from arsenic exposure included intervention time, intervention method, dosage, age of animals, and the sample source from which the indexes were estimated. Our meta-analysis effectively summarized a wide range of studies and detected a positive relationship between arsenic exposure and oxidative damage. These data provide a scientific basis for the prevention and treatment of arsenic poisoning.

  13. Oxidative damage and sensitivity to nociceptive stimulus and opioids in aging rats

    PubMed Central

    Raut, Atul; Ratka, Anna

    2009-01-01

    Oxidative stress contributes to aging and may cause alterations in pain and analgesia. Knowledge about effects of oxidative stress on the opioid system is very limited. This project was designed to determine the relationship between age-related oxidative damage and opioid antinocicpetion. Three age groups of male Fischer 344 rats were tested for pain sensitivity and responses to morphine and fentanyl using the hot plate method. Oxidative stress markers in various brain regions were measured. With advancing age, nociceptive threshold and antinociceptive effects of opioids decreased significantly. There was a significant negative correlation between morphine antinociception and protein oxidation in cortex, striatum, and midbrain (r2 = 0.73, 0.87, and 0.77, respectively), and lipid peroxidation in cerebral cortex, hippocampus, and striatum (r2 = 0.73, 0.61 and 0.71, respectively). Similar correlation was observed between oxidative stress markers and fentanyl antinociception. These findings demonstrate that the age-related increase in oxidative damage in brain is associated with a significant decrease in the antinociceptive effects of opioids. PMID:17997197

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

    SciTech Connect

    Liu Shukun; Wu Mei; Zhang Zunzhen

    2010-08-01

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

  15. Influence of dietary carbohydrate on zinc-deficiency-induced changes in oxidative defense mechanisms and tissue oxidative damage in rats.

    PubMed

    Kim, S H; Keen, C L

    1999-10-01

    The aim of this study was to determine the effect of dietary carbohydrate type on the expression of zinc (Zn) deficiency in rats with respect to tissue oxidative damage and defense mechanisms. Rats were fed diets containing adequate (+Zn) or low concentrations (-Zn) of Zn. Both fructose- and glucose-based diets were tested. Pair-fed controls were also studied to evaluate changes in the oxidative defense system which are secondary to Zn-deficiency-induced anorexia. Plasma and liver Zn concentrations and CuZn superoxide dismutase activities were lower in the -Zn rats than in the +Zn rats. Liver glutathione (GSH) and disulfide glutathione concentrations were higher in the -Zn rats than in the +Zn rats; this difference was most pronounced in the fructose groups. Liver and heart selenium glutathione peroxidase (Se-GSH-Px) activities were lower in the -Zn-fructose group than in the +Zn-fructose group. Liver Se-GSH-Px activity was higher in the fructose groups than in the glucose groups. Liver GSH reductase (GSH-Red) activity was lower in the -Zn-fructose group than in its control group. Liver glutamine synthetase activity was lower in the -Zn-glucose group and in the fructose groups than in the glucose control group. Liver thiobarbituric acid reactive substance (TBARS) production was similar among the groups. Collectively, these results support the concept that Zn deficiency can result in an impaired oxidant defense system. Based on the observation that pair-fed control animals also showed evidence of oxidative damage, we suggest that one factor that contributes to the effect of Zn deficiency is the reduction in caloric intake that occurs in these animals. Fructose feeding resulted in increased activities of several of the oxidant defense enzymes. Protein oxidative damage assessed by glutamine synthetase activity was increased by both Zn deficiency and fructose feeding.

  16. Disinfection by-products effect on swimmers oxidative stress and respiratory damage.

    PubMed

    Llana-Belloch, Salvador; Priego Quesada, Jose Ignacio; Pérez-Soriano, Pedro; Lucas-Cuevas, Ángel G; Salvador-Pascual, Andrea; Olaso-González, Gloria; Moliner-Martinez, Yolanda; Verdú-Andres, Jorge; Campins-Falco, Pilar; Gómez-Cabrera, M Carmen

    2016-08-01

    Disinfection by-products (DBPs) are generated through the reaction of chlorine with organic and inorganic matter in indoor swimming pools. Different DBPs are present in indoor swimming pools. This study evaluated the effects of different chlorinated formations in oxidative stress and lung damage in 20 swimmers after 40 min of aerobic swimming in 3 indoor pools with different characteristics. Biological samples were collected to measure lung damage (serum-surfactant-associated proteins A and B), oxidative stress parameters (plasma protein carbonylation and malondialdehyde, and whole-blood glutathione oxidation), and swimming exertion values (blood lactate) before and after exercise. Free chlorine and combined chlorine in water, and chlorine in air samples were determined in all the swimming pools. Chlorination as disinfection treatment led to the formation of chloramines in water samples, mainly mono- and dichloramine. However, free chlorine was the predominate species in ultraviolet-treated swimming pool. Levels of total chlorine increased as a function of the swimming activity in chlorinated swimming pools. The lower quality of the installation resulted in a higher content of total chlorine, especially in air samples, and therefore a higher exposure of the swimmer to DBPs. However, the concentration level of chlorinated DBPs did not result in significant variation in serum-surfactant-associated proteins A and oxidative stress parameters in swimmers. In conclusion, the quality of the installation affected the DBPs concentration; however, it did not lead to lung epithelial damage and oxidative stress parameters in swimmers.

  17. Platelet-rich plasma reduces the oxidative damage determined by a skeletal muscle contusion in rats.

    PubMed

    Martins, Rodrigo Pereira; Hartmann, Diane Duarte; de Moraes, Jefferson Potiguara; Soares, Felix Alexandre Antunes; Puntel, Gustavo Orione

    2016-12-01

    Platelet-rich plasma (PRP) has received increasing attention and is widely used in clinical practice in order to stimulate human tissue healing. Contusions are very common injuries observed in sports and affect the function of the musculoskeletal system. This study investigated the effects of PRP on the oxidative damage determined by a contusion induced in gastrocnemius muscle of rats. PRP was injected intramuscularly immediately after injury and every 48 h, and the biochemical analysis was performed 1, 3, 5, or 7 days after the contusion onset in order to evaluate the changes characteristics of the healing process. The contusion increased the levels of oxidative stress markers such as thiobarbituric acid reactive substances and oxidized dichlorofluorescein both in skeletal muscle tissue and erythrocytes preparations, and PRP treatment significantly reduced these oxidative damage markers. Furthermore, the contusion decreased the cellular viability in the site of the lesion and PRP was effective in diminishing this effect. Moreover, PRP increased the levels of enzymatic antioxidants superoxide dismutase and catalase activities in the injured muscle, and also the non-protein thiols (-SH) group levels in erythrocytes. In conclusion PRP, in the form that was used in this study, was able to modulate the oxidative damage determined by a classical skeletal muscle injury possibly by reducing the impairment of myocytes mitochondrial function and improving their endogenous antioxidant defense systems.

  18. XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage.

    PubMed

    Liu, Jing; Fang, Hongbo; Chi, Zhenfen; Wu, Zan; Wei, Di; Mo, Dongliang; Niu, Kaifeng; Balajee, Adayabalam S; Hei, Tom K; Nie, Linghu; Zhao, Yongliang

    2015-06-23

    Xeroderma pigmentosum group D (XPD/ERCC2) encodes an ATP-dependent helicase that plays essential roles in both transcription and nucleotide excision repair of nuclear DNA, however, whether or not XPD exerts similar functions in mitochondria remains elusive. In this study, we provide the first evidence that XPD is localized in the inner membrane of mitochondria, and cells under oxidative stress showed an enhanced recruitment of XPD into mitochondrial compartment. Furthermore, mitochondrial reactive oxygen species production and levels of oxidative stress-induced mitochondrial DNA (mtDNA) common deletion were significantly elevated, whereas capacity for oxidative damage repair of mtDNA was markedly reduced in both XPD-suppressed human osteosarcoma (U2OS) cells and XPD-deficient human fibroblasts. Immunoprecipitation-mass spectrometry analysis was used to identify interacting factor(s) with XPD and TUFM, a mitochondrial Tu translation elongation factor was detected to be physically interacted with XPD. Similar to the findings in XPD-deficient cells, mitochondrial common deletion and oxidative damage repair capacity in U2OS cells were found to be significantly altered after TUFM knock-down. Our findings clearly demonstrate that XPD plays crucial role(s) in protecting mitochondrial genome stability by facilitating an efficient repair of oxidative DNA damage in mitochondria.

  19. Arsenosugar induced blood and brain oxidative stress, DNA damage and neurobehavioral impairments.

    PubMed

    Bin Sayeed, Muhammad Shahdaat; Ratan, Md; Hossen, Farhad; Hassan, Faizule; Faisal, Mohammad; Kadir, Mohammad Fahim

    2013-02-01

    The effect of Arsenosugar on motor function and contextual memory-related to place and event; the extent of DNA damage and oxidative stress in male swiss albino mice was investigated. Passive avoidance test was used for memory test; rota motor test was used for motor function. Several biochemical parameters were used for assessing oxidative stress due to arsenosugar ingestion. Decreased passive avoidance time and decreased retention time in rotating rod indicated disruption of normal neurobehavior. Significant dose-dependent DNA damage was found in mice blood and brain. Decreased super oxide dismutase, increased lipid peroxidation, decreased protein sulfohydryl content, increased protein carbonyl content in blood and hippocampal tissue; glutathione in blood and glutathione peroxidase in hippocampal tissue indicated the ability of arsenosugar to cause oxidative stress. This study concludes with evidence that arsenosugar ingestion causes higher oxidative stress, increases DNA damage in the blood and hippocampus in vivo. This might be responsible for the dysfunction of cognitive and motor functions. However, further investigation is suggested for deciphering the biomolecular mechanism.

  20. Aluminum phosphide-induced genetic and oxidative damages in rats: attenuation by Laurus nobilis leaf extract.

    PubMed

    Türkez, Hasan; Toğar, Başak

    2013-08-01

    Aluminum phosphide (AlP) is a colorless, flammable, liquefied pesticide that is commonly used to control insects, nematodes, weeds, and pathogens in crops, forests, ornamental nurseries, and wood products. Early investigations of AlP-poisoned mammalian cells led to the proposed involvement of oxidative damage in its toxicity mechanism. Therefore, this study was aimed to evaluate the effect of Laurus nobilis (L) leaf extract (LNE) against AlP-induced genetic and oxidative damages in rats. Selected animals were assigned to four groups (n = 6), namely, group A: control (only distilled water is injected); group B: AlP (4 mg kg(-1) injected intraperitoneally (i.p.)); group C: LNE (200 mg kg(-1) injected i.p.), and group D: AlP plus LNE, respectively. The experimental period lasted for 14 successive days. Chromosomal aberrations (CAs) and micronucleus (MN) assay were used for monitoring genotoxic damage. In addition, biochemical parameters such as total antioxidant capacity (TAC) and total oxidative status (TOS) were examined in serum samples to determine oxidative damage. Our results indicated that AlP caused increase in CA and MN assay rates and alterations in TAC and TOS levels when compared with control group. On the contrary, LNE did not change the rates of both the analyzed cytogenetic end points and led to increase in TAC level. Moreover, we observed that LNE suppressed the genetic damage by AlP to bone marrow cells in vivo. Interestingly AlP-induced oxidative stress was also strongly reduced by LNE. The results of the present study indicated that the protective effect of LNE might be ascribable to its antioxidant and free radical scavenging properties.

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

    SciTech Connect

    Pina-Guzman, B.; Solis-Heredia, M.J.; Rojas-Garcia, A.E.; Uriostegui-Acosta, M.; Quintanilla-Vega, B. . E-mail: mquintan@cinvestav.mx

    2006-10-15

    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{sub 3} (CMA{sub 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{sub 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.

  2. Bromination of deoxycytidine by eosinophil peroxidase: A mechanism for mutagenesis by oxidative damage of nucleotide precursors

    PubMed Central

    Henderson, Jeffrey P.; Byun, Jaeman; Williams, Michelle V.; McCormick, Michael L.; Parks, William C.; Ridnour, Lisa A.; Heinecke, Jay W.

    2001-01-01

    Oxidants generated by eosinophils during chronic inflammation may lead to mutagenesis in adjacent epithelial cells. Eosinophil peroxidase, a heme enzyme released by eosinophils, generates hypobromous acid that damages tissue in inflammatory conditions. We show that human eosinophils use eosinophil peroxidase to produce 5-bromodeoxycytidine. Flow cytometric, immunohistochemical, and mass spectrometric analyses all demonstrated that 5-bromodeoxycytidine generated by eosinophil peroxidase was taken up by cultured cells and incorporated into genomic DNA as 5-bromodeoxyuridine. Although previous studies have focused on oxidation of chromosomal DNA, our observations suggest another mechanism for oxidative damage of DNA. In this scenario, peroxidase-catalyzed halogenation of nucleotide precursors yields products that subsequently can be incorporated into DNA. Because the thymine analog 5-BrUra mispairs with guanine in DNA, generation of brominated pyrimidines by eosinophils might constitute a mechanism for cytotoxicity and mutagenesis at sites of inflammation. PMID:11172002

  3. Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration

    PubMed Central

    Pietrofesa, Ralph A; Turowski, Jason B; Arguiri, Evguenia; Milovanova, Tatyana N; Solomides, Charalambos C; Thom, Stephen R; Christofidou-Solomidou, Melpo

    2013-01-01

    Background Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Methods Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Results Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly

  4. Oxidative DNA damage induced by benz[a]anthracene dihydrodiols in the presence of dihydrodiol dehydrogenase.

    PubMed

    Seike, Kazuharu; Murata, Mariko; Hirakawa, Kazutaka; Deyashiki, Yoshihiro; Kawanishi, Shosuke

    2004-11-01

    Tobacco smoke and polluted air are risk factors for lung cancer and contain many kinds of polycyclic aromatic hydrocarbons (PAHs) including benzo[a]pyrene (B[a]P) and benz[a]anthracene (BA). BA, as well as B[a]P, is assessed as probably carcinogenic to humans (IARC group 2A). BA is metabolized to several dihydrodiols. Dihydrodiol dehydrogenase (DD), a member of the aldo-keto reductase superfamily, catalyzes NAD(P)+-linked oxidation of dihydrodiols of aromatic hydrocarbons to corresponding catechols. To clarify the role of DD on PAH carcinogenesis, we examined oxidative DNA damage induced by trans-dihydrodiols of BA and B[a]P treated with DD using 32P-5'-end-labeled DNA fragments obtained from the human p53 tumor suppressor gene. In addition, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an indicator of oxidative DNA damage, in calf thymus DNA by using HPLC with an electrochemical detector. DD-catalyzed BA-1,2-dihydrodiol caused Cu(II)-mediated DNA damage including 8-oxodG formation in the presence of NAD+. BA-1,2-dihydrodiol induced a Fpg sensitive and piperidine labile G lesion at the 5'-ACG-3' sequence complementary to codon 273 of the human p53 tumor suppressor gene, which is known as a hotspot. DNA damage was inhibited by catalase and bathocuproine, suggesting the involvement of H2O2 and Cu(I). The observation of NADH production by UV-visible spectroscopy suggested that DD catalyzed BA-1,2-dihydrodiol most efficiently to the corresponding catechol among the PAH-dihydrodiols tested. A time-of-flight mass spectroscopic study showed that the catechol form of BA-1,2-dihydrodiol formed after DD treatment. In conclusion, BA-1,2-dihydrodiol can induce DNA damage more efficiently than B[a]P-7,8-dihydrodiol and other BA-dihydrodiols in the presence of DD. The reaction mechanism on oxidative DNA damage may be explained by theoretical calculations with an enthalpy change of dihydrodiols and oxidation potential of their catechol forms. DD

  5. FSH protects mouse granulosa cells from oxidative damage by repressing mitophagy

    PubMed Central

    Shen, Ming; Jiang, Yi; Guan, Zhiqiang; Cao, Yan; Sun, Shao-chen; Liu, Honglin

    2016-01-01

    Oxidative stress has been implicated in triggering granulosa cell (GC) death during follicular atresia. Recent studies suggested that follicle-stimulating hormone (FSH) has a pivotal role in protecting GCs from oxidative injury, although the exact mechanism remains largely unknown. Here, we report that FSH promotes GC survival by inhibiting oxidative stress-induced mitophagy. The loss of GC viability caused by oxidative stress was significantly reduced after FSH treatment, which was correlated with impaired activation of mitophagy upon oxidative stress. Compared with FSH treatment, blocking mitophagy displayed approximate preventive effect on oxidative stress-induced GC death, but FSH did not further restore viability of cells pretreated with mitophagy inhibitor. Importantly, FSH suppressed the induction of serine/threonine kinase PINK1 during oxidative stress. This inhibited the mitochondrial translocation of the E3 ligase Parkin, which is required for the subsequent clearance of mitochondria, and ultimately cell death via mitophagy. In addition, knocking down PINK1 using RNAi confirmed the role of the FSH-PINK1-Parkin-mitophagy pathway in regulating GC survival under oxidative conditions. These findings introduce a novel physiological function of FSH in protecting GCs against oxidative damage by targeting PINK1-Parkin-mediated mitophagy. PMID:27901103

  6. Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

    PubMed Central

    Yuvaraju, Priya; Beegam, Sumaya; Fahim, Mohamed A.; Ali, Badreldin H.

    2017-01-01

    CeO2 nanoparticles (CeO2 NPs) which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h) effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg) on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL-) 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs. PMID:28392888

  7. Oxidative stress contributes to cobalt oxide nanoparticles-induced cytotoxicity and DNA damage in human hepatocarcinoma cells

    PubMed Central

    Alarifi, Saud; Ali, Daoud; Y, Al Omar Suliman; Ahamed, Maqusood; Siddiqui, Maqsood A; Al-Khedhairy, Abdulaziz A

    2013-01-01

    Background Cobalt oxide nanoparticles (Co3O4NPs) are increasingly recognized for their utility in biological applications, magnetic resonance imaging, and drug delivery. However, little is known about the toxicity of Co3O4NPs in human cells. Methods We investigated the possible mechanisms of genotoxicity induced by Co3O4NPs in human hepatocarcinoma (HepG2) cells. Cell viability, reactive oxygen species (ROS), glutathione, thiobarbituric acid reactive substance, apoptosis, and DNA damage were assessed in HepG2 cells after Co3O4NPs and Co2+ exposure. Results Co3O4NPs elicited a significant (P < 0.01) reduction in glutathione with a concomitant increase in lipid hydroperoxide, ROS generation, superoxide dismutase, and catalase activity after 24- and 48-hour exposure. Co3O4NPs had a mild cytotoxic effect in HepG2 cells; however, it induced ROS and oxidative stress, leading to DNA damage, a probable mechanism of genotoxicity. The comet assay showed a statistically significant (P < 0.01) dose- and time-related increase in DNA damage for Co3O4NPs, whereas Co2+ induced less change than Co3O4NPs but significantly more than control. Conclusion Our results demonstrated that Co3O4NPs induced cytotoxicity and genotoxicity in HepG2 cells through ROS and oxidative stress. PMID:23326189

  8. Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

    PubMed

    Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

    2016-06-01

    Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P < 0.001) increase in glycosylated hemoglobin, glucose, homeostasis model of insulin resistance, and pro-inflammatory cytokines. Serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly (P < 0.001) decreased in diabetic rats. Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P < 0.001) down-regulated in testes of diabetic rats, an effect which was significantly increased after administration of taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

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

    SciTech Connect

    Zana, Marianna . E-mail: mzana@freemail.hu; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Vetro, Agnes; Pakaski, Magdolna; Janka, Zoltan; Kalman, Janos; Szabo, Krisztina; Szucs, Peter; Varkonyi, Agnes; Boda, Krisztina; Rasko, Istvan

    2006-06-30

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

  10. Protective Effects of Extracts from Fructus rhodomyrti against Oxidative DNA Damage In Vitro and In Vivo

    PubMed Central

    Ke, Yuebin; Xu, Xinyun; Wu, Shuang; Huang, Juan; Misra, Hara; Li, Yunbo

    2013-01-01

    Objective. To evaluate the potential protective effects of extracts from Fructus rhodomyrti (FR) against oxidative DNA damage using a cellular system and the antioxidant ability on potassium bromate- (KBrO3-) mediated oxidative stress in rats. Methods. The effects of FR on DNA damage induced by hydrogen peroxide (H2O2) were evaluated by comet assay in primary spleen lymphocytes cultures. The effects of FR on the activities of SOD, CAT, and GPx and the levels of GSH, hydroperoxides, and 8-OHdG were determined in the plasma and tissues of rats treated with KBrO3. Results. FR was shown to effectively protect against DNA damage induced by H2O2  in vitro, and the maximum protective effect was observed when FR was diluted 20 times. Endogenous antioxidant status, namely, the activities of SOD, CAT, and GPx and the levels of GSH were significantly decreased in the plasma, the liver, and the kidney of the KBrO3-treated rats, while the pretreatment of FR prevented the decreases of these parameters. In addition, the pretreatment of FR was also able to prevent KBrO3-induced increases in the levels of hydroperoxides and 8-OHdG in the plasma, the liver, and the kidney in rats. Conclusions. Our findings suggested that FR might act as a chemopreventive agent with antioxidant properties offering effective protection against oxidative DNA damage in a concentration-dependent manner in vitro and in vivo. PMID:24089629

  11. CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes

    PubMed Central

    Liu, Lie-Gang; Yan, Hong; Yao, Ping; Zhang, Wen; Zou, Li-Jun; Song, Fang-Fang; Li, Ke; Sun, Xiu-Fa

    2005-01-01

    AIM: To observe the relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and cytochrome P450 2E1 (CYP2E1) activity, in order to address if inhibition of CYP2E1 could attenuate ethanol-induced cellular damage. METHODS: The dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) exposures of primary human cultured hepatocytes to ethanol were carried out. CYP2E1 activity and protein expression were detected by spectrophotometer and Western blot analysis respectively. Hepatotoxicity was investigated by determination of lactate dehydrogenase (LDH) and aspartate transaminase (AST) level in hepatocyte culture supernatants, as well as the intracellular formation of malondialdehyde (MDA). RESULTS: A dose-and time-dependent response between ethanol exposure and CYP2E1 activity in human hepatocytes was demonstrated. Moreover, there was a time-dependent increase of CYP2E1 protein after 100 mmol/L ethanol exposure. Meanwhile, ethanol exposure of hepatocytes caused a time-dependent increase of cellular MDA level, LDH, and AST activities in supernatants. Furthermore, the inhibitor of CYP2E1, diallyl sulfide (DAS) could partly attenuate the increases of MDA, LDH, and AST in human hepatocytes. CONCLUSION: A positive relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and CYP2E1 activity was exhibited, and the inhibition of CYP2E1 could partly attenuate ethanol-induced oxidative damage. PMID:16052683

  12. Chaga mushroom extract inhibits oxidative DNA damage in human lymphocytes as assessed by comet assay.

    PubMed

    Park, Yoo Kyoung; Lee, Hyang Burm; Jeon, Eun-Jae; Jung, Hack Sung; Kang, Myung-Hee

    2004-01-01

    The Chaga mushroom (Inonotus obliquus) is claimed to have beneficial properties for human health, such as anti-bacterial, anti-allergic, anti-inflammatory and antioxidant activities. The antioxidant effects of the mushroom may be partly explained by protection of cell components against free radicals. We evaluated the effect of aqueous Chaga mushroom extracts for their potential for protecting against oxidative damage to DNA in human lymphocytes. Cells were pretreated with various concentrations (10, 50, 100 and 500 microg/mL) of the extract for 1 h at 37 degrees C. Cells were then treated with 100 microM of H2O2 for 5 min as an oxidative stress. Evaluation of oxidative damage was performed using single-cell gel electrophoresis for DNA fragmentation (Comet assay). Using image analysis, the degree of DNA damage was evaluated as the DNA tail moment. Cells pretreated with Chaga extract showed over 40% reduction in DNA fragmentation compared with the positive control (100 micromol H2O2 treatment). Thus, Chaga mushroom treatment affords cellular protection against endogenous DNA damage produced by H2O2.

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

    SciTech Connect

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

    2008-12-01

    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 {approx} 1.3 fold in the nuclear protein extracts (NE) and {approx} 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 {approx} 1.5 fold higher, whereas in the MEs it was {approx} 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

  14. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome.

    PubMed

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-08-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both -/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress.

  15. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome

    PubMed Central

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both −/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress. PMID:24769161

  16. Scaring as a tool to alleviate crop damage by geese: Revealing differences between farmers' perceptions and the scale of the problem.

    PubMed

    Simonsen, Caroline E; Tombre, Ingunn M; Madsen, Jesper

    2017-03-01

    Expanding populations of farmland foraging geese are causing escalating conflict with agriculture. We used questionnaires to investigate farmers´ perceptions in mid-Norway of spring staging geese and the extent to which they attempt to reduce pasture damage by goose scaring. We predicted farmers' scaring effort (a measure of dissatisfaction) to increase on fields closer to goose roosting sites where goose grazing intensity was highest (measured by dropping counts). Results showed no such relationship, suggesting that farmers' perception of goose use was not linked to actual goose use, but influenced by sociological factors and individual opinion. These results confirm the need to distribute subsidies/compensation to affected farmers based upon quantifiable measures of goose use rather than complaint levels. To avoid further conflict escalation, it is equally important that managers are aware of farmers´ perceptions and their causes, to effectively target communication about policies and measures to mitigate goose-agriculture problems.

  17. Oxidative DNA damage background estimated by a system model of base excision repair

    SciTech Connect

    Sokhansanj, B A; Wilson, III, D M

    2004-05-13

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level based on measuring 8-oxoguanine lesions as a biomarker have led to estimates varying over 3-4 orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our results show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  18. Oxidative stress and genetic damage among workers exposed primarily to organophosphate and pyrethroid pesticides.

    PubMed

    Zepeda-Arce, Rigoberto; Rojas-García, Aurora Elizabeth; Benitez-Trinidad, Alma; Herrera-Moreno, José Francisco; Medina-Díaz, Irma Martha; Barrón-Vivanco, Briscia S; Villegas, Germán Pier; Hernández-Ochoa, Isabel; Sólis Heredia, María de Jesús; Bernal-Hernández, Yael Y

    2017-02-24

    The indiscriminate use of pesticides in agriculture and public health campaigns has been associated with an increase of oxidative stress and DNA damage, resulting in health outcomes. Some defense mechanisms against free radical-induced oxidative damage include the antioxidant enzyme systems. The aim of this study was to determine the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and the relationship of antioxidant enzyme levels with DNA damage among sprayers (workers) occupationally exposed to pesticides. The determinations of MDA and antioxidant enzymes were performed spectrophotometrically. The genotoxic effects were evaluated using the comet assay. The results showed a marginally significant decrease in SOD and CAT activities in the high exposure group compared to the control group. For MDA, statistically significant differences were found among people working long term vs. those working temporarily (P = 0.02) as sprayers. In the moderate exposure group, a positive correlation was observed between MDA levels and GPx activity. In the high exposure group, a negative correlation was observed between GR and CAT activities, and between MDA levels and GPx activities. Furthermore, in the high exposure group, a positive correlation between DNA damage parameters and MDA levels was observed. The results suggest an important role of antioxidant enzymes for the protection of DNA damage caused by occupational exposure to pesticides.

  19. Magnesium Supplementation Diminishes Peripheral Blood Lymphocyte DNA Oxidative Damage in Athletes and Sedentary Young Man

    PubMed Central

    Petrović, Jelena; Stanić, Dušanka; Dmitrašinović, Gordana; Plećaš-Solarović, Bosiljka; Ignjatović, Svetlana; Batinić, Bojan; Popović, Dejana

    2016-01-01

    Sedentary lifestyle is highly associated with increased risk of cardiovascular disease, obesity, and type 2 diabetes. It is known that regular physical activity has positive effects on health; however several studies have shown that acute and strenuous exercise can induce oxidative stress and lead to DNA damage. As magnesium is essential in maintaining DNA integrity, the aim of this study was to determine whether four-week-long magnesium supplementation in students with sedentary lifestyle and rugby players could prevent or diminish impairment of DNA. By using the comet assay, our study demonstrated that the number of peripheral blood lymphocytes (PBL) with basal endogenous DNA damage is significantly higher in rugby players compared to students with sedentary lifestyle. On the other hand, magnesium supplementation significantly decreased the number of cells with high DNA damage, in the presence of exogenous H2O2, in PBL from both students and rugby players, and markedly reduced the number of cells with medium DNA damage in rugby players compared to corresponding control nonsupplemented group. Accordingly, the results of our study suggest that four-week-long magnesium supplementation has marked effects in protecting the DNA from oxidative damage in both rugby players and in young men with sedentary lifestyle. Clinical trial is registered at ANZCTR Trial Id: ACTRN12615001237572. PMID:27042258

  20. Modafinil effects on behavior and oxidative damage parameters in brain of wistar rats.

    PubMed

    Ornell, Felipe; Valvassori, Samira S; Steckert, Amanda V; Deroza, Pedro F; Resende, Wilson R; Varela, Roger B; Quevedo, João

    2014-01-01

    The effects of modafinil (MD) on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg). Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses.

  1. Oxidative DNA damage background estimated by a system model of base excision repair.

    PubMed

    Sokhansanj, Bahrad A; Wilson, David M

    2004-08-01

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level, based on measuring 8-oxoguanine lesions as a biomarker, have led to estimates that vary over three to four orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our findings show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  2. Ascorbic acid and beta-carotene reduce stress-induced oxidative organ damage in rats.

    PubMed

    Esrefoglu, M; Akinci, A; Taslidere, E; Elbe, H; Cetin, A; Ates, B

    2016-10-01

    Antioxidants are potential therapeutic agents for reducing stress-induced organ damage. We investigated the effects of ascorbic acid and β-carotene on oxidative stress-induced cerebral, cerebellar, cardiac and hepatic damage using microscopy and biochemistry. Male Wistar albino rats were divided into five groups: untreated control, stressed, stressed + saline, stressed + ascorbic acid and stressed + β-carotene. The rats in the stressed groups were subjected to starvation, immobilization and cold. The histopathological damage scores for the stressed and stressed + saline groups were higher than those of the control group for all organs examined. The histopathological damage scores and mean tissue malondialdehyde levels for the groups treated with antioxidants were lower than those for the stressed and stressed + saline groups. Mean tissue superoxide dismutase activities for groups that received antioxidants were higher than those for the stressed + saline group for most organs evaluated. Ascorbic acid and β-carotene can reduce stress-induced organ damage by both inhibiting lipid oxidation and supporting the cellular antioxidant defense system.

  3. Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage.

    PubMed

    Schürmann, Nura; Forrer, Pascal; Casse, Olivier; Li, Jiagui; Felmy, Boas; Burgener, Anne-Valérie; Ehrenfeuchter, Nikolaus; Hardt, Wolf-Dietrich; Recher, Mike; Hess, Christoph; Tschan-Plessl, Astrid; Khanna, Nina; Bumann, Dirk

    2017-01-23

    Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.

  4. Modafinil Effects on Behavior and Oxidative Damage Parameters in Brain of Wistar Rats

    PubMed Central

    Valvassori, Samira S.; Steckert, Amanda V.; Deroza, Pedro F.; Resende, Wilson R.; Varela, Roger B.

    2014-01-01

    The effects of modafinil (MD) on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg). Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses. PMID:25431526

  5. Omega 3 polyunsaturated fatty acids enhance the protective effect of levetiracetam against seizures, cognitive impairment and hippocampal oxidative DNA damage in young kindled rats.

    PubMed

    Abdel-Wahab, Basel A; Shaikh, Ibrahim A; Khateeb, Masood M; Habeeb, Shafiuddin M

    2015-08-01

    Levetiracetam (LEV) is a unique, effective, relatively safe antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A). This study aimed to explore the effect of combined treatment of LEV with omega 3 (OM3) on cognitive impairment and hippocampal oxidative stress and DNA damage induced by seizures in the PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats pretreated with single and combined treatment of LEV (30mg/kg, i.p.) and OM3 (200mg/kg, p.o.). Pretreatment with LEV and OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, the increase in hippocampal glutamate, malondialdehyde and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase and superoxide dismutase activities induced by PTZ kindling, significantly decreased. These effects were higher with combined treatment of LEV with OM3 and significantly more than the observed effects of single LEV or OM3. In conclusion, the combined treatment of LEV with OM3 is more effective in seizure control and alleviating the cognitive impairment induced by PTZ kindling in the young rat model, the effects that result from the decrease in hippocampal oxidative stress and DNA damage which can be attributed to the antioxidant properties of both LEV and OM3. These results may be promising for the use of LEV and OM3 combination in the treatment of epileptic children.

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

    PubMed Central

    Wang, Yi; Liang, Xinying; Chen, Yaqi; Zhao, Xiaoping

    2016-01-01

    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. PMID:26981165

  7. Nondestructive Evaluation (NDE) for Characterizing Oxidation Damage in Cracked Reinforced Carbon-Carbon

    NASA Technical Reports Server (NTRS)

    Roth, Don J.; Jacobson, Nathan S.; Rauser, Richard W.; Wincheski, Russell A.; Walker, James L.; Cosgriff, Laura A.

    2010-01-01

    In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter's thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using nondestructive evaluation (NDE) methods. These specimens were heat treated in air at 1143 C and 1200 C to create cavities in the carbon substrate underneath the coating as oxygen reacted with the carbon and resulted in its consumption. The cavities varied in diameter from approximately 1 to 3mm. Single-sided NDE methods were used because they might be practical for on-wing inspection, while X-ray micro-computed tomography (CT) was used to measure cavity sizes in order to validate oxidation models under development for carbon-carbon materials. An RCC sample having a naturally cracked coating and subsequent oxidation damage was also studied with X-ray micro-CT. This effort is a follow-on study to one that characterized NDE methods for assessing oxidation damage in an RCC sample with drilled holes in the coating.

  8. Nondestructive Evaluation (NDE) for Characterizing Oxidation Damage in Cracked Reinforced Carbon-Carbon (RCC)

    NASA Technical Reports Server (NTRS)

    Roth, Don J.; Rauser, Richard W.; Jacobson, Nathan S.; Wincheski, Russell A.; Walker, James L.; Cosgriff, Laura A.

    2009-01-01

    In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter's thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using nondestructive evaluation (NDE) methods. These specimens were heat treated in air at 1143 and 1200 C to create cavities in the carbon substrate underneath the coating as oxygen reacted with the carbon and resulted in its consumption. The cavities varied in diameter from approximately 1 to 3 mm. Single-sided NDE methods were used since they might be practical for on-wing inspection, while x-ray micro-computed tomography (CT) was used to measure cavity sizes in order to validate oxidation models under development for carbon-carbon materials. An RCC sample having a naturally-cracked coating and subsequent oxidation damage was also studied with x-ray micro-CT. This effort is a follow-on study to one that characterized NDE methods for assessing oxidation damage in an RCC sample with drilled holes in the coating.

  9. Cerium Oxide Nanoparticles Reduce Microglial Activation and Neurodegenerative Events in Light Damaged Retina

    PubMed Central

    Fiorani, Lavinia; Passacantando, Maurizio; Santucci, Sandro; Di Marco, Stefano; Bisti, Silvia; Maccarone, Rita

    2015-01-01

    The first target of any therapy for retinal neurodegeneration is to slow down the progression of the disease and to maintain visual function. Cerium oxide or ceria nanoparticles reduce oxidative stress, which is known to play a pivotal role in neurodegeneration. Our aim was to investigate whether cerium oxide nanoparticles were able to mitigate neurodegeneration including microglial activation and related inflammatory processes induced by exposure to high intensity light. Cerium oxide nanoparticles were injected intravitreally or intraveinously in albino Sprague-Dawley rats three weeks before exposing them to light damage of 1000 lux for 24 h. Electroretinographic recordings were performed a week after light damage. The progression of retinal degeneration was evaluated by measuring outer nuclear layer thickness and TUNEL staining to quantify photoreceptors death. Immunohistochemical analysis was used to evaluate retinal stress, neuroinflammatory cytokines and microglial activation. Only intravitreally injected ceria nanoparticles were detected at the level of photoreceptor outer segments 3 weeks after the light damage and electoretinographic recordings showed that ceria nanoparticles maintained visual response. Moreover, this treatment reduced neuronal death and “hot spot” extension preserving the outer nuclear layer morphology. It is noteworthy that in this work we demonstrated, for the first time, the ability of ceria nanoparticles to reduce microglial activation and their migration toward outer nuclear layer. All these evidences support ceria nanoparticles as a powerful therapeutic agent in retinal neurodegenerative processes. PMID:26469804

  10. Cerium Oxide Nanoparticles Reduce Microglial Activation and Neurodegenerative Events in Light Damaged Retina.

    PubMed

    Fiorani, Lavinia; Passacantando, Maurizio; Santucci, Sandro; Di Marco, Stefano; Bisti, Silvia; Maccarone, Rita

    2015-01-01

    The first target of any therapy for retinal neurodegeneration is to slow down the progression of the disease and to maintain visual function. Cerium oxide or ceria nanoparticles reduce oxidative stress, which is known to play a pivotal role in neurodegeneration. Our aim was to investigate whether cerium oxide nanoparticles were able to mitigate neurodegeneration including microglial activation and related inflammatory processes induced by exposure to high intensity light. Cerium oxide nanoparticles were injected intravitreally or intraveinously in albino Sprague-Dawley rats three weeks before exposing them to light damage of 1000 lux for 24 h. Electroretinographic recordings were performed a week after light damage. The progression of retinal degeneration was evaluated by measuring outer nuclear layer thickness and TUNEL staining to quantify photoreceptors death. Immunohistochemical analysis was used to evaluate retinal stress, neuroinflammatory cytokines and microglial activation. Only intravitreally injected ceria nanoparticles were detected at the level of photoreceptor outer segments 3 weeks after the light damage and electoretinographic recordings showed that ceria nanoparticles maintained visual response. Moreover, this treatment reduced neuronal death and "hot spot" extension preserving the outer nuclear layer morphology. It is noteworthy that in this work we demonstrated, for the first time, the ability of ceria nanoparticles to reduce microglial activation and their migration toward outer nuclear layer. All these evidences support ceria nanoparticles as a powerful therapeutic agent in retinal neurodegenerative processes.

  11. Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment.

    PubMed

    Reckziegel, Patrícia; Dias, Verônica Tironi; Benvegnú, Dalila; Boufleur, Nardeli; Silva Barcelos, Raquel Cristine; Segat, Hecson Jesser; Pase, Camila Simonetti; Dos Santos, Clarissa Marques Moreira; Flores, Erico Marlon Moraes; Bürger, Marilise Escobar

    2011-05-30

    We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning.

  12. Oxidative damage in gills and liver in Nile tilapia (Oreochromis niloticus) exposed to diazinon.

    PubMed

    Toledo-Ibarra, G A; Díaz Resendiz, K J G; Ventura-Ramón, G H; González-Jaime, F; Vega-López, A; Becerril-Villanueva, E; Pavón, L; Girón-Pérez, M I

    2016-10-01

    Agricultural activity demands the use of pesticides for plague control and extermination. In that matter, diazinon is one of the most widely used organophosphorus pesticides (OPs). Despite its benefits, the use of OPs in agricultural activities can also have negative effects since the excessive use of these substances can represent a major contamination problem for water bodies and organisms that inhabit them. The aim of this paper was to evaluate oxidative damage in lipids and proteins of Nile tilapia (Oreochromis niloticus) exposed acutely to diazinon (0.97, 1.95 and 3.95ppm) for 12 or 24h. The evaluation of oxidative damage was determined by quantifying lipid hydroperoxides (Fox method) and oxidized proteins (DNPH method). The data from this study suggest that diazinon induces a concentration-dependent oxidative damage in proteins, but not lipids, of the liver and gills of Nile tilapia. Furthermore, the treatment leads to a decrease in the concentration of total proteins, which can have serious consequences in cell physiology and fish development.

  13. A new potent natural antioxidant mixture provides global protection against oxidative skin cell damage.

    PubMed

    Jorge, A T S; Arroteia, K F; Lago, J C; de Sá-Rocha, V M; Gesztesi, J; Moreira, P L

    2011-04-01

    Oxidative stress occurs when there is an over production of free radicals and cells are not able to neutralize them by their own antioxidant mechanisms. These excess of free radicals will attack cellular macromolecules leading to cell damage, function impairment or death. Because of that, antioxidant substances have been largely used in products to offer complementary protection. In this study a new mixture of three known antioxidants (cocoa, green tea and alpha-tocopherol) was evaluated and its antioxidant protection was assessed focusing on its capacity to protect main cell macromolecules. Results have shown that it has a high antioxidant capacity by protecting lipids, DNA and proteins against oxidative damage. The antioxidant effect of the mixture on cells was also investigated and it was able to reduce oxidative stress generated by lipopolisacharide in human fibroblasts. Finally, as the mixture has proved to be highly antioxidant, its effect on cell senescence was evaluated, and it was demonstrated that fibroblasts in culture had delayed senescence when treated with these actives on a mixture. All results together provide important data about a new antioxidant mixture that uses a small amount of actives and is able to protect cell against oxidative damages in a global way.

  14. Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet.

    PubMed

    Xu, Li; Huang, Danping; Hu, Qiaolin; Wu, Jing; Wang, Yizhen; Feng, Jie

    2015-06-28

    To assess the effects of betaine on hepatic lipid accumulation and investigate the underlying mechanism, thirty-two male Sprague-Dawley rats weighing 100 (sd 2·50) g were divided into four groups, and started on one of four treatments: basal diet, basal diet with betaine administration, high-fat diet and high-fat diet with betaine administration. The results showed that no significant difference of body weight was found among experimental groups. Compared with high-fat diet-fed rats, a betaine supplementation decreased (P< 0·05) hepatic TAG accumulation induced by high-fat diet, which was also supported by hepatic histology results. Additionally, hepatic betaine-homocysteine methyltransferase concentration [corrected] as well as its mRNA abundance and lecithin level were found increased (P< 0·05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P< 0·05) concentration [corrected] of hepatic carnitine palmitoyltransferase 1 (CPT1) compared with high-fat diet-fed rats. High-fat diet inhibited (P< 0·05) the gene expression of hepatic PPARα and CPT1. However, betaine administration in high-fat diet-fed rats elevated (P< 0·05) the gene expression of PPARα and CPT1. Moreover, concentration, gene and protein expressions of hepatic fibroblast growth factor 21 (FGF21) were increased (P< 0·05) in response to betaine administration in high-fat diet group; meanwhile the gene expression of hepatic AMP-activated protein kinase was increased (P< 0·05) as well. The results suggest that betaine administration enhanced hepatic lipid export and fatty acid oxidation in high-fat diet-fed rats, thus effectively alleviating fat accumulation in the liver.

  15. Estimation of oxidative DNA damage in man from urinary excretion of repair products.

    PubMed

    Loft, S; Poulsen, H E

    1998-01-01

    DNA is constantly damaged and repaired in living cells. The repair products of the oxidative DNA lesions, i.e. oxidised nucleosides and bases, are poor substrates for the enzymes involved in nucleotide synthesis, are fairly water soluble, and generally excreted into the urine without further metabolism. Among the possible products, 8-oxo-2'-deoxyguanosine, 8-oxoguanine, thymine glycol, thymidine glycol and, 5-hydroxymethyluracil have so far been identified in urine. It should be emphasised that the excretion of the repair products in urine represents the average rate of damage in the total body whereas the level of oxidised bases in nuclear DNA is a concentration measurement in that specific tissue/cells in the moment of sampling. The rate of oxidative DNA modifications has been studied in humans by means of the repair products as urinary biomarkers, particularly with respect to 8-oxo-2'-deoxyguanosine. The data obtained so far indicate that the important determinants of the oxidative damage rate include tobacco smoking, oxygen consumption and some inflammatory diseases whereas diet composition, energy restriction and antioxidant supplements have but a minimal influence, possibly with the exception of yet unidentified phytochemicals, e.g. from cruciferous vegetables. The data are consistent with the experimentally based notion that oxidative DNA damage is an important mutagenic and apparently carcinogenic factor. However, the proof of a causal relationship in humans is still warranted. In the future the use of biomarkers may provide this evidence and allow further investigations on the qualitative and quantitative importance of oxidative DNA modification and carcinogenesis in man, as well as elucidate possible preventive measures.

  16. Prophylaxis with Bacopa monnieri attenuates acrylamide induced neurotoxicity and oxidative damage via elevated antioxidant function.

    PubMed

    Shinomol, George Kunnel; Raghunath, Narayanareddy; Bharath, Muchukunte Mukunda Srinivas; Muralidhara

    2013-03-01

    Acrylamide (ACR) is a water-soluble, vinyl monomer that has multiple chemical and industrial applications. Exposure to ACR causes neuropathy and associated neurological defects including gait abnormalities and skeletal muscle weakness, due to impaired neurotransmitter release and eventual neurodegeneration. Using in vivo and in vitro models, we examined whether oxidative events are involved in ACR-mediated neurotoxicity and whether these could be prevented by natural plant extracts. Administration (i.p.) of ACR in mice (40 mg/kg bw/ d for 5d) induced significant oxidative damage in the brain cortex and liver as evidenced by elevated lipid peroxidation, reactive oxygen species and protein carbonyls. This was associated with lowered antioxidant activities including antioxidant enzymes (catalase, glutathione-s-transferase) and reduced glutathione (GSH) compared to untreated controls. Similarly, exposure of N27 neuronal cells in culture to ACR (1-5 mM) caused dose-dependent neuronal death and lowered GSH. Interestingly, dietary supplementation with the leaf powder of Bacopa monnieri (BM) (which possesses neuroprotective properties and nootropic activity) in mice for 30 days offered significant protection against ACR toxicity and oxidative damage in vivo. Similarly, pretreatment with BM protected the N27 cells against ACR-induced cell death and associated oxidative damage. Co-treatment and pre-treatment of Drosophila melanogaster with BM extract protected against ACR-induced locomotor dysfunction and GSH depletion. We infer that BM displays prophylactic effects against ACR induced oxidative damage and neurotoxicity with potential therapeutic application in human pathology associated with neuropathy.

  17. Curcumin attenuates oxidative stress following downhill running-induced muscle damage.

    PubMed

    Kawanishi, Noriaki; Kato, Kouki; Takahashi, Masaki; Mizokami, Tsubasa; Otsuka, Yoshihiko; Imaizumi, Atsushi; Shiva, Daisuke; Yano, Hiromi; Suzuki, Katsuhiko

    2013-11-22

    Downhill running causes muscle damage, and induces oxidative stress and inflammatory reaction. Recently, it is shown that curcumin possesses anti-oxidant and anti-inflammatory potentials. Interestingly, curcumin reduces inflammatory cytokine concentrations in skeletal muscle after downhill running of mice. However, it is not known whether curcumin affects oxidative stress after downhill running-induced muscle damage. Therefore, the purpose of this study was to investigate the effects of curcumin on oxidative stress following downhill running induced-muscle damage. We also investigated whether curcumin affects macrophage infiltration via chemokines such as MCP-1 and CXCL14. Male C57BL/6 mice were divided into four groups; rest, rest plus curcumin, downhill running, or downhill running plus curcumin. Downhill running mice ran at 22 m/min, -15% grade on the treadmill for 150 min. Curcumin (3mg) was administered in oral administration immediately after downhill running. Hydrogen peroxide concentration and NADPH-oxidase mRNA expression in the downhill running mice were significantly higher than those in the rest mice, but these variables were significantly attenuated by curcumin administration in downhill running mice. In addition, mRNA expression levels of MCP-1, CXCL14 and F4/80 reflecting presence of macrophages in the downhill running mice were significantly higher than those in the rest mice. However, MCP-1 and F4/80 mRNA expression levels were significantly attenuated by curcumin administration in downhill running mice. Curcumin may attenuate oxidative stress following downhill running-induced muscle damage.

  18. A review of the impact of oxidative stress and some antioxidant therapies on renal damage.

    PubMed

    Tamay-Cach, F; Quintana-Pérez, J C; Trujillo-Ferrara, J G; Cuevas-Hernández, R I; Del Valle-Mondragón, L; García-Trejo, E M; Arellano-Mendoza, M G

    2016-01-01

    An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.

  19. Mass spectrometric quantification of amino acid oxidation products identifies oxidative mechanisms of diabetic end-organ damage

    PubMed Central

    Vivekanadan-Giri, Anuradha; Wang, Jeffrey H.; Byun, Jaeman

    2010-01-01

    Diabetes mellitus is increasingly prevalent worldwide. Diabetic individuals are at markedly increased risk for premature death due to cardiovascular disease. Furthermore, substantial morbidity results from microvascular complications which include retinopathy, nephropathy, and neuropathy. Clinical studies involving diabetic patients have suggested that degree of diabetic hyperglycemia correlates with risk of complications. Recent evidence implicates a central role for oxidative stress and vascular inflammation in all forms of insulin resistance, obesity, diabetes and its complications. Although, glucose promotes glycoxidation reactions in vitro and products of glycoxidation and lipoxidation are elevated in plasma and tissue in diabetics, the exact relationships among hyperglycemia, the diabetic state, and oxidative stress are not well-understood. Using a combination of in vitro and in vivo experiments, we have identified amino acid oxidation markers that serve as molecular fingerprints of specific oxidative pathways. Quantification of these products utilizing highly sensitive and specific gas chromatography/mass spectrometry in animal models of diabetic complications and in humans has provided insights in oxidative pathways that result in diabetic complications. Our studies strongly support the hypothesis that unique oxidants are generated in the microenvironment of tissues vulnerable to diabetic damage. Potential therapies interrupting these reactive pathways in target tissue are likely to be beneficial in preventing diabetic complications. PMID:18752069

  20. Plasticity and ductility in graphene oxide through a mechanochemically induced damage tolerance mechanism

    PubMed Central

    Wei, Xiaoding; Mao, Lily; Soler-Crespo, Rafael A.; Paci, Jeffrey T.; Espinosa, Horacio D.

    2015-01-01

    The ability to bias chemical reaction pathways is a fundamental goal for chemists and material scientists to produce innovative materials. Recently, two-dimensional materials have emerged as potential platforms for exploring novel mechanically activated chemical reactions. Here we report a mechanochemical phenomenon in graphene oxide membranes, covalent epoxide-to-ether functional group transformations that deviate from epoxide ring-opening reactions, discovered through nanomechanical experiments and density functional-based tight binding calculations. These mechanochemical transformations in a two-dimensional system are directionally dependent, and confer pronounced plasticity and damage tolerance to graphene oxide monolayers. Additional experiments on chemically modified graphene oxide membranes, with ring-opened epoxide groups, verify this unique deformation mechanism. These studies establish graphene oxide as a two-dimensional building block with highly tuneable mechanical properties for the design of high-performance nanocomposites, and stimulate the discovery of new bond-selective chemical transformations in two-dimensional materials. PMID:26289729

  1. Active sensing and damage detection using piezoelectric zinc oxide-based nanocomposites.

    PubMed

    Meyers, Frederick N; Loh, Kenneth J; Dodds, John S; Baltazar, Arturo

    2013-05-10

    This study investigated the design and performance of piezoelectric nanocomposite-based interdigitated transducers (IDTs) for active sensing and damage detection. First, thin films that are highly piezoelectric and mechanically flexible were designed by embedding zinc oxide (ZnO) nanoparticles in a poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) piezo-polymer matrix. Second, the suspended nanoparticle solutions were then spin coated onto patterned comb electrodes to fabricate the IDTs. The films were then poled to align their electric domains and to increase their permanent piezoelectricity. Upon IDT fabrication, its sensing and actuation of Lamb waves on an aluminum pipe was validated. These results were also compared to data obtained from commercial Macro Fiber Composite IDT transducers. In the last phase of this work, damage detection was demonstrated by mounting these nanocomposite sensors and actuators (using a pitch-catch setup) onto an aluminum pipe and plate. Damage was simulated by tightening a band clamp around the pipe and by drilling holes in the plate. A damage index calculation was used to compare results corresponding to different levels of damage applied to the plate (i.e., different drilled hole depths), and good correlation was observed. Thus, ZnO/PVDF-TrFE transducers were shown to have the potential for use as piezoelectric transducers for structural health monitoring and damage detection.

  2. Active sensing and damage detection using piezoelectric zinc oxide-based nanocomposites

    NASA Astrophysics Data System (ADS)

    Meyers, Frederick N.; Loh, Kenneth J.; Dodds, John S.; Baltazar, Arturo

    2013-05-01

    This study investigated the design and performance of piezoelectric nanocomposite-based interdigitated transducers (IDTs) for active sensing and damage detection. First, thin films that are highly piezoelectric and mechanically flexible were designed by embedding zinc oxide (ZnO) nanoparticles in a poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) piezo-polymer matrix. Second, the suspended nanoparticle solutions were then spin coated onto patterned comb electrodes to fabricate the IDTs. The films were then poled to align their electric domains and to increase their permanent piezoelectricity. Upon IDT fabrication, its sensing and actuation of Lamb waves on an aluminum pipe was validated. These results were also compared to data obtained from commercial Macro Fiber Composite IDT transducers. In the last phase of this work, damage detection was demonstrated by mounting these nanocomposite sensors and actuators (using a pitch-catch setup) onto an aluminum pipe and plate. Damage was simulated by tightening a band clamp around the pipe and by drilling holes in the plate. A damage index calculation was used to compare results corresponding to different levels of damage applied to the plate (i.e., different drilled hole depths), and good correlation was observed. Thus, ZnO/PVDF-TrFE transducers were shown to have the potential for use as piezoelectric transducers for structural health monitoring and damage detection.

  3. Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice

    PubMed Central

    Song, Ming-Fen; Li, Yun-Shan; Kasai, Hiroshi; Kawai, Kazuaki

    2012-01-01

    Several mechanisms regarding the adverse health effects of nanomaterials have been proposed. Among them, oxidative stress is considered to be one of the most important. Many in vitro studies have shown that nanoparticles generate reactive oxygen species, deplete endogenous antioxidants, alter mitochondrial function and produce oxidative damage in DNA. 8-Hydroxy-2'-deoxyguanosine is a major type of oxidative DNA damage, and is often analyzed as a marker of oxidative stress in human and animal studies. In this study, we focused on the in vivo toxicity of metal oxide and silver nanoparticles. In particular, we analyzed the induction of micronucleated reticulocyte formation and oxidative stress in mice treated with nanoparticles (CuO, Fe3O4, Fe2O3, TiO2, Ag). For the micronucleus assay, peripheral blood was collected from the tail at 0, 24, 48 and 72 h after an i.p. injection of nanoparticles. Following the administration of nanoparticles by i.p. injection to mice, the urinary 8-hydroxy-2'-deoxyguanosine levels were analyzed by the HPLC-ECD method, to monitor the oxidative stress. The levels of 8-hydroxy-2'-deoxyguanosine in liver DNA were also measured. The results showed increases in the reticulocyte micronuclei formation in all nanoparticle-treated groups and in the urinary 8-hydroxy-2'-deoxyguanosine levels. The 8-hydroxy-2'-deoxyguanosine levels in the liver DNA of the CuO-treated group increased in a dose-dependent manner. In conclusion, the metal nanoparticles caused genotoxicity, and oxidative stress may be responsible for the toxicity of these metal nanoparticles. PMID:22573923

  4. Association of oxidative DNA damage, protein oxidation and antioxidant function with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers during fetal circulation.

    PubMed

    Negi, Reena; Pande, Deepti; Karki, Kanchan; Kumar, Ashok; Khanna, Ranjana S; Khanna, Hari D

    2014-02-05

    Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation.

  5. Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A

    PubMed Central

    Yang, Chunying; Sengupta, Shiladitya; Hegde, Pavana M.; Mitra, Joy; Jiang, Shuai; Holey, Brooke; Sarker, Altaf H.; Tsai, Miaw-Sheue; Hegde, Muralidhar L.; Mitra, Sankar

    2017-01-01

    Reactive oxygen species (ROS), generated both endogenously and in response to exogenous stress, induce point mutations by mis-replication of oxidized bases and other lesions in the genome. Repair of these lesions via base excision repair (BER) pathway maintains genomic fidelity. Regulation of the BER pathway for mutagenic oxidized bases, initiated by NEIL1 and other DNA glycosylases at the chromatin level remains unexplored. Whether single nucleotide (SN)-BER of a damaged base requires histone deposition or nucleosome remodeling is unknown, unlike nucleosome reassembly which is shown to be required for other DNA repair processes. Here we show that chromatin assembly factor (CAF)-1 subunit A (CHAF1A), the p150 subunit of the histone H3/H4 chaperone, and its partner anti-silencing function protein 1A (ASF1A), which we identified in human NEIL1 immunoprecipitation complex, transiently dissociate from chromatin bound NEIL1 complex in G1 cells after induction of oxidative base damage. CHAF1A inhibits NEIL1 initiated repair in vitro. Subsequent restoration of the chaperone-BER complex in cell, presumably after completion of repair, suggests that histone chaperones sequester the repair complex for oxidized bases in non-replicating chromatin, and allow repair when oxidized bases are induced in the genome. PMID:27794043

  6. Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection.

    PubMed

    Pregi, Nicolás; Belluscio, Laura María; Berardino, Bruno Gabriel; Castillo, Daniela Susana; Cánepa, Eduardo Tomás

    2017-01-01

    cAMP response element-binding (CREB) protein is a cellular transcription factor that mediates responses to different physiological and pathological signals. Using a model of human neuronal cells we demonstrate herein, that CREB is phosphorylated after oxidative stress induced by hydrogen peroxide. This phosphorylation is largely independent of PKA and of the canonical phosphoacceptor site at ser-133, and is accompanied by an upregulation of CREB expression at both mRNA and protein levels. In accordance with previous data, we show that CREB upregulation promotes cell survival and that its silencing results in an increment of apoptosis after oxidative stress. Interestingly, we also found that CREB promotes DNA repair after treatment with hydrogen peroxide. Using a cDNA microarray we found that CREB is responsible for the regulation of many genes involved in DNA repair and cell survival after oxidative injury. In summary, the neuroprotective effect mediated by CREB appears to follow three essential steps following oxidative injury. First, the upregulation of CREB expression that allows sufficient level of activated and phosphorylated protein is the primordial event that promotes the induction of genes of the DNA Damage Response. Then and when the DNA repair is effective, CREB induces detoxification and survival genes. This kinetics seems to be important to completely resolve oxidative-induced neuronal damages.

  7. Buffet Load Alleviation

    NASA Technical Reports Server (NTRS)

    Ryall, T. G.; Moses, R. W.; Hopkins, M. A.; Henderson, D.; Zimcik, D. G.; Nitzsche, F.

    2004-01-01

    High performance aircraft are, by their very nature, often required to undergo maneuvers involving high angles of attack. Under these conditions unsteady vortices emanating from the wing and the fuselage will impinge on the twin fins (required for directional stability) causing excessive buffet loads, in some circumstances, to be applied to the aircraft. These loads result in oscillatory stresses, which may cause significant amounts of fatigue damage. Active control is a possible solution to this important problem. A full-scale test was carried out on an F/A-18 fuselage and fins using piezoceramic actuators to control the vibrations. Buffet loads were simulated using very powerful electromagnetic shakers. The first phase of this test was concerned with the open loop system identification whereas the second stage involved implementing linear time invariant control laws. This paper looks at some of the problems encountered as well as the corresponding solutions and some results. It is expected that flight trials of a similar control system to alleviate buffet will occur as early as 2001.

  8. Role of oxidative DNA damage in mitochondrial dysfunction and Huntington's disease pathogenesis.

    PubMed

    Ayala-Peña, Sylvette

    2013-09-01

    Huntington's disease (HD) is a neurodegenerative disorder with an autosomal dominant expression pattern and typically a late-onset appearance. HD is a movement disorder with a heterogeneous phenotype characterized by involuntary dance-like gait, bioenergetic deficits, motor impairment, and cognitive and psychiatric deficits. Compelling evidence suggests that increased oxidative stress and mitochondrial dysfunction may underlie HD pathogenesis. However, the exact mechanisms underlying mutant huntingtin-induced neurological toxicity remain unclear. The objective of this paper is to review recent literature regarding the role of oxidative DNA damage in mitochondrial dysfunction and HD pathogenesis.

  9. Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage.

    PubMed

    Kageyama, Yusuke; Zhang, Zhongyan; Roda, Ricardo; Fukaya, Masahiro; Wakabayashi, Junko; Wakabayashi, Nobunao; Kensler, Thomas W; Reddy, P Hemachandra; Iijima, Miho; Sesaki, Hiromi

    2012-05-14

    Mitochondria divide and fuse continuously, and the balance between these two processes regulates mitochondrial shape. Alterations in mitochondrial dynamics are associated with neurodegenerative diseases. Here we investigate the physiological and cellular functions of mitochondrial division in postmitotic neurons using in vivo and in vitro gene knockout for the mitochondrial division protein Drp1. When mouse Drp1 was deleted in postmitotic Purkinje cells in the cerebellum, mitochondrial tubules elongated due to excess fusion, became large spheres due to oxidative damage, accumulated ubiquitin and mitophagy markers, and lost respiratory function, leading to neurodegeneration. Ubiquitination of mitochondria was independent of the E3 ubiquitin ligase parkin in Purkinje cells lacking Drp1. Treatment with antioxidants rescued mitochondrial swelling and cell death in Drp1KO Purkinje cells. Moreover, hydrogen peroxide converted elongated tubules into large spheres in Drp1KO fibroblasts. Our findings suggest that mitochondrial division serves as a quality control mechanism to suppress oxidative damage and thus promote neuronal survival.

  10. N-Acetyl-L-cysteine Protects the Enterocyte against Oxidative Damage by Modulation of Mitochondrial Function

    PubMed Central

    Xiao, Hao; Wu, Miaomiao; Shao, Fangyuan; Guan, Guiping; Huang, Bo

    2016-01-01

    The neonatal small intestine is susceptible to damage caused by oxidative stress. This study aimed to evaluate the protective role of antioxidant N-acetylcysteine (NAC) in intestinal epithelial cells against oxidative damage induced by H2O2. IPEC-J2 cells were cultured in DMEM-H with NAC and H2O2. After 2-day incubation, IPEC-J2 cells were collected for analysis of DNA synthesis, antioxidation capacity, mitochondrial respiration, and cell apoptosis. The results showed that H2O2 significantly decreased (P < 0.05) proliferation rate, mitochondrial respiration, and antioxidation capacity and increased cell apoptosis and the abundance of associated proteins, including cytochrome C, Bcl-XL, cleaved caspase-3, and total caspase-3. NAC supplementation remarkably increased (P < 0.05) proliferation rate, antioxidation capacity, and mitochondrial bioenergetics but decreased cell apoptosis. These findings indicate that NAC might rescue the intestinal injury induced by H2O2. PMID:28003713

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

    PubMed Central

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

    2013-01-01

    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. PMID:23966597

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

    PubMed

    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.

  13. Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage.

    PubMed

    Rathore, Khizr I; Kerr, Bradley J; Redensek, Adriana; López-Vales, Rubèn; Jeong, Suh Young; Ponka, Prem; David, Samuel

    2008-11-26

    CNS injury-induced hemorrhage and tissue damage leads to excess iron, which can cause secondary degeneration. The mechanisms that handle this excess iron are not fully understood. We report that spinal cord contusion injury (SCI) in mice induces an "iron homeostatic response" that partially limits iron-catalyzed oxidative damage. We show that ceruloplasmin (Cp), a ferroxidase that oxidizes toxic ferrous iron, is important for this process. SCI in Cp-deficient mice demonstrates that Cp detoxifies and mobilizes iron and reduces secondary tissue degeneration and functional loss. Our results provide new insights into how astrocytes and macrophages handle iron after SCI. Importantly, we show that iron chelator treatment has a delayed effect in improving locomotor recovery between 3 and 6 weeks after SCI. These data reveal important aspects of the molecular control of CNS iron homeostasis after SCI and suggest that iron chelator therapy may improve functional recovery after CNS trauma and hemorrhagic stroke.

  14. Oxidative Stress, Inflammation, and DNA Damage Responses Elicited by Silver, Titanium Dioxide, and Cerium Oxide Nanomaterials

    EPA Science Inventory

    Previous literature on the biological effects of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigating potential pathways. Here we examine time-sensitive biological response pathways affected by engineered nanoma...

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

    PubMed

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

    2015-09-01

    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined.

  16. Oxidative stress and DNA damage in horses naturally infected with Theileria equi.

    PubMed

    Radakovic, M; Davitkov, D; Borozan, S; Stojanovic, S; Stevanovic, J; Krstic, V; Stanimirovic, Z

    2016-11-01

    The aim of this study was to determine the concentrations of oxidative stress parameters and DNA damage in horses infected by Theileria equi. Initial screening of 110 horses with duplex PCR enabled the selection of 30 infected horses with T. equi and 30 free of infection (control). Specimens from the 60 horses were further analysed by determining the following oxidative stress parameters: extent of haemolysis (EH), plasma free haemoglobin (PHb), catalase (CAT), Cu,Zn superoxide dismutase (SOD1), paraoxonase (PON1), nitrite (NO2(-)), total nitrate and nitrite (NOx), malondialdehyde (MDA) and free thiol groups (-SH). In addition, relative distribution of lactate dehydrogenase (LDH1-LDH5) activity and the DNA-damaging effects of T. equi infection were evaluated. Compared to control horses, horses infected with T. equi had significantly higher SOD1 activities (P <0.05) and PHb (P <0.01), NO2(-) (P <0.001), NOx (P <0.05) and MDA concentrations (P <0.001), and significantly lower EH (P <0.001), CAT (P <0.01) and PON1 (P <0.001) activities, and thiol group concentrations (P <0.05). The comet assay demonstrated significantly increased DNA damage in T. equi infected cells compared to non-infected cells (P <0.001). Infected horses had significantly increased LDH5 isoenzyme activities (P <0.05). There was higher production of ROS/RNS in T. equi-infected horses, which resulted in changes in osmotic fragility, damage to lipids, proteins and DNA, haemolysis and hepatocellular damage. Oxidative stress in horses naturally infected with T. equi could contribute to the pathogenesis of the infection.

  17. G6PD protects from oxidative damage and improves healthspan in mice

    PubMed Central

    Nóbrega-Pereira, Sandrina; Fernandez-Marcos, Pablo J.; Brioche, Thomas; Gomez-Cabrera, Mari Carmen; Salvador-Pascual, Andrea; Flores, Juana M.; Viña, Jose; Serrano, Manuel

    2016-01-01

    Reactive oxygen species (ROS) are constantly generated by cells and ROS-derived damage contributes to ageing. Protection against oxidative damage largely relies on the reductive power of NAPDH, whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here, we report a transgenic mouse model with moderate overexpression of human G6PD under its endogenous promoter. Importantly, G6PD-Tg mice have higher levels of NADPH, lower levels of ROS-derived damage, and better protection from ageing-associated functional decline, including extended median lifespan in females. The G6PD transgene has no effect on tumour development, even after combining with various tumour-prone genetic alterations. We conclude that a modest increase in G6PD activity is beneficial for healthspan through increased NADPH levels and protection from the deleterious effects of ROS. PMID:26976705

  18. Review of structural influences on the laser damage thresholds of oxide coatings

    SciTech Connect

    Hacker, E.; Lauth, H.; Weibbrodt, P.

    1996-12-31

    The laser damage thresholds (LDT) of optical coatings lie, as a rule, markedly below those of the respective bulk materials. This is due to diverse specific real structure properties with regard to composition, crystallography, microstructure and the physico-chemical structure of the interfaces. These properties depend in a highly complex and sensitive way on the substrate treatment, coating techniques and deposition conditions. With evaporated and sputtered oxide coatings as example, some correlations between structural thin film properties (e.g. crystallography, microstructure, anisotropy, chemical composition, defects) and the ultraviolet (248 nm) or near infrared (1064 nm) laser damage thresholds are discussed with concern to a further increase of the damage resistance. It is evident from data that an approach to the problem requires complex investigations of the technology-structure-properties relationships.

  19. Analysis of cavitation damage on the Space Shuttle main engine high pressure oxidizer turbopump

    NASA Technical Reports Server (NTRS)

    Stinebring, D. R.

    1985-01-01

    The performance of the Space Shuttle Main Engines (SSME) has met or exceeded specifications. However, the durability for selected components has not met the desired lifetime criteria. Thus, the High-Pressure Oxidizer Turbopump (HPOTP) has experienced cavitation erosion problems in a number of locations in the pump. An investigation was conducted, taking into account an analysis of the cavitation damage, the development of a flow model for the pump, and the recommendation of design changes which would increase the life expectancy of the unit. The present paper is concerned with the cavitation damage analysis. A model is presented which relates the heavy damage on the housing and over the inducer blades to unsteady blade surface cavitation. This cavitation occurs on the inducer blades in the wakes downstream of the pump inlet housing vanes.

  20. An analysis of pump cavitation damage. [Space Shuttle main engine high pressure oxidizer turbopump

    NASA Technical Reports Server (NTRS)

    Brophy, M. C.; Stinebring, D. R.; Billet, M. L.

    1985-01-01

    The cavitation assessment for the space shuttle main engine high pressure oxidizer turbopump is documented. A model of the flow through the pump was developed. Initially, a computational procedure was used to analyze the flow through the inlet casing including the prediction of wakes downstream of the casing vanes. From these flow calculations, cavitation patterns on the inducer blades were approximated and the damage rate estimated. The model correlates the heavy damage on the housing and over the inducer with unsteady blade surface cavitation. The unsteady blade surface cavitation is due to the large incidence changes caused by the wakes of the upstream vanes. Very high cavitation damage rates are associated with this type of cavitation. Design recommendations for reducing the unsteady cavitation include removing the set of vanes closest to the inducer and modifying the remaining vanes.

  1. A study of pump cavitation damage. [space shuttle main engine high pressure oxidizer turbopump

    NASA Technical Reports Server (NTRS)

    Brophy, M. C.; Stinebring, D. R.; Billet, M. L.

    1983-01-01

    The cavitation assessment for the space shuttle main engine high pressure oxidizer turbopump is documented. A model of the flow through the pump was developed. Initially, a computational procedure was used to analyze the flow through the inlet casing including the prediction of wakes downstream of the casing vanes. From these flow calculations, cavitation patterns on the inducer blades were approximated and the damage rate estimated. The model correlates the heavy damage on the housing and over the inducer with unsteady blade surface cavitation. The unsteady blade surface cavitation is due to the large incidence changes caused by the wakes of the upstream vanes. Very high cavitation damage rates are associated with this type of cavitation. Design recommendations for reducing the unsteady cavitation include removing the set of vanes closest to the inducer and modifying the remaining vanes.

  2. Age-related differences in experimental stroke: possible involvement of mitochondrial dysfunction and oxidative damage.

    PubMed

    Li, Nanlin; Kong, Xiangwei; Ye, Ruidong; Yang, Qianzi; Han, Junliang; Xiong, Lize

    2011-06-01

    Age is the single most important risk factor for cerebral stroke. Unfortunately, the effect of age on ischemic brain damage is less clear. In this study, we sought to examine the potential influence of aging on the histologic and functional outcomes after ischemia. Juvenile (4 weeks of age), young adult (4 months of age), mid-aged (11-12 months of age), and aged (18-19 months of age) mice were subjected to transient middle cerebral artery occlusion. There was no remarkable difference of infarct volume on postoperative days 1 and 3. However, on postoperative day 7, aged mice exhibited significantly worsened infarct volume compared with juvenile and young mice. Intriguingly, the increase of infarct volume was most prominent in the striatal area rather than in cortex. Accordingly, aged mice displayed a slower and incomplete functional recovery after stroke. We further evaluated the effects of aging on the oxidative damage and mitochondrial dysfunction following ischemia. Brain tissues were assayed for lipid, DNA, and protein peroxidation products, mitochondrial enzyme activities, mitochondrial membrane potential, production of reactive oxygen species, and antioxidant activities. Aging was associated with declined mitochondrial function and antioxidant detoxification following ischemia, thereby inducing a deteriorated oxidative damage. Regional subanalyses demonstrated that, in accordance with infarct area, the pro-oxidant/antioxidant imbalance occurred more prominently in subcortical areas. Collectively, these findings suggest mitochondria-mediated oxidative damage may be involved in the age-related aggravated injury in subcortical areas. Mitochondrial protection could be a promising target for neuroprotective therapy, especially in the aged population.

  3. Integrated assessment of oxidative stress and DNA damage in earthworms (Eisenia fetida) exposed to azoxystrobin.

    PubMed

    Han, Yingnan; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Xie, Hui; Zhang, Shumin

    2014-09-01

    Azoxystrobin has been widely used in recent years. The present study investigated the oxidative stress and DNA damage effects of azoxystrobin on earthworms (Eisenia fetida). Earthworms were exposed to different azoxystrobin concentrations in an artificial soil (0, 0.1, 1, and 10mg/kg) and sampled on days 7, 14, 21, and 28. Superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POD), glutathione-S-transferase (GST), reactive oxygen species (ROS), and malondialdehyde (MDA) content were measured by an ultraviolet spectrophotometer to determine the antioxidant responses and lipid peroxidation. Single cell gel electrophoresis (SCGE) was used to detect DNA damage in the coelomocytes. Compared with these in the controls, earthworms exposed to azoxystrobin had excess ROS accumulation and greater SOD, POD, and GST activity while the opposite trend occurred for CAT activity. MDA content increased after 14-day exposure, and DNA damage was enhanced with an increase in the concentration of azoxystrobin. In conclusion, azoxystrobin caused oxidative stress leading to lipid peroxidation and DNA damage in earthworms.

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

    PubMed

    Skipper, Anthony; Sims, Jennifer N; Yedjou, Clement G; Tchounwou, Paul B

    2016-01-02

    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.

  5. Calculation of the stabilization energies of oxidatively damaged guanine base pairs with guanine.

    PubMed

    Suzuki, Masayo; Kino, Katsuhito; Morikawa, Masayuki; Kobayashi, Takanobu; Komori, Rie; Miyazawa, Hiroshi

    2012-06-01

    DNA is constantly exposed to endogenous and exogenous oxidative stresses. Damaged DNA can cause mutations, which may increase the risk of developing cancer and other diseases. G:C-C:G transversions are caused by various oxidative stresses. 2,2,4-Triamino-5(2H)-oxazolone (Oz), guanidinohydantoin (Gh)/iminoallantoin (Ia) and spiro-imino-dihydantoin (Sp) are known products of oxidative guanine damage. These damaged bases can base pair with guanine and cause G:C-C:G transversions. In this study, the stabilization energies of these bases paired with guanine were calculated in vacuo and in water. The calculated stabilization energies of the Ia:G base pairs were similar to that of the native C:G base pair, and both bases pairs have three hydrogen bonds. By contrast, the calculated stabilization energies of Gh:G, which form two hydrogen bonds, were lower than the Ia:G base pairs, suggesting that the stabilization energy depends on the number of hydrogen bonds. In addition, the Sp:G base pairs were less stable than the Ia:G base pairs. Furthermore, calculations showed that the Oz:G base pairs were less stable than the Ia:G, Gh:G and Sp:G base pairs, even though experimental results showed that incorporation of guanine opposite Oz is more efficient than that opposite Gh/Ia and Sp.

  6. Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice.

    PubMed

    Singh, Anant; Kumar, Anil

    2008-04-01

    Sleep deprivation is considered as a risk factor for various diseases. Sleep deprivation leads to behavioral, hormonal, neurochemical and biochemical alterations in the animals. The present study was designed to explore the possible involvement of GABAergic mechanism in protective effect of alprazolam against 72h sleep deprivation-induced behavior alterations and oxidative damage in mice. In the present study, sleep deprivation caused anxiety-like behavior, weight loss, impaired ambulatory movements and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep-deprived mice brain. Treatment with alprazolam (0.25 and 0.5 mg/kg, ip) significantly improved behavioral alterations. Biochemically, alprazolam treatment significantly restored depleted reduced glutathione, catalase activity, reversed raised lipid peroxidation and nitrite level. Combination of flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) with lower dose of alprazolam (0.25mg/kg) significantly antagonized protective effect of alprazolam. However, combination of muscimol (0.05 mg/kg) with alprazolam (0.25 mg/kg, ip) potentiated protective effect of alprazolam. On the basis of these results, it might be suggested that alprazolam might produce protective effect by involving GABAergic system against sleep deprivation-induced behavior alterations and related oxidative damage.

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

    PubMed Central

    Bayram, Fahri; Bitgen, Nazmiye; Ata, Sibel; Hamurcu, Zuhal; Baskol, Gulden

    2017-01-01

    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. PMID:28373882

  8. A Dose-Response Study of Arsenic Exposure and Markers of Oxidative Damage in Bangladesh

    PubMed Central

    Harper, Kristin N.; Liu, Xinhua; Hall, Megan N.; Ilievski, Vesna; Oka, Julie; Calancie, Larissa; Slavkovich, Vesna; Levy, Diane; Siddique, Abu; Alam, Shafiul; Mey, Jacob L.; van Geen, Alexander; Graziano, Joseph H.; Gamble, Mary V.

    2014-01-01

    Objective To evaluate the dose-response relationship between arsenic exposure and markers of oxidative damage in Bangladeshi adults. Methods We recruited 378 participants drinking from wells assigned to five water arsenic exposure categories; the distribution of subjects was as follows: 1) <10 μg/L (n=76); 2) 10–100 μg/L (n=104); 3) 101–200 μg/L (n=86); 4) 201–300 μg/L (n=67); and 5) > 300 μg/L (n=45). Arsenic concentrations were measured in well water, as well as in urine and blood. Urinary 8-oxo-2’-deoxyguanosine (8-oxo-dG) and plasma protein carbonyls were measured to assess oxidative damage. Results None of our measures of arsenic exposure were significantly associated with protein carbonyl or 8-oxo-dG levels. Conclusions We found no evidence to support a significant relationship between chronic exposure to arsenic-contaminated drinking water and biomarkers of oxidative damage among Bangladeshi adults. PMID:24854259

  9. Selective vulnerability of preterm white matter to oxidative damage defined by F2-isoprostanes.

    PubMed

    Back, Stephen A; Luo, Ning Ling; Mallinson, Rebecca A; O'Malley, Jean P; Wallen, Linda D; Frei, Balz; Morrow, Jason D; Petito, Carol K; Roberts, Charles T; Murdoch, Geoffrey H; Montine, Thomas J

    2005-07-01

    Periventricular white matter injury (PWMI) is the leading cause of cerebral palsy and chronic neurological disability in survivors of prematurity. Despite the large number of affected children, the pathogenetic mechanisms related to PWMI remain controversial. Through studies of 33 human autopsy brains, we determined that early PWMI was related to oxidative damage that particularly targeted the oligodendrocyte lineage, whereas other neuronal and glial cell types were markedly more resistant. F(2)-isoprostanes, an arachidinate metabolite/lipid peroxidation marker of oxidative damage, were significantly increased in early PWMI lesions but not in cerebral cortex. That deleterious lipid peroxidation accompanied early PWMI was supported by similar increases in F(2)-isoprostanes levels in the cerebral cortex from term infants with hypoxic-ischemic cortical injury. Detection of F(4)-neuroprostanes, a neuronal-specific oxidative damage marker, confirmed that neuroaxonal elements were resistant to injury in cerebral cortex and white matter. Significant protein nitration was not detected in PWMI lesions by 3-nitrotyrosine staining. Significant cellular degeneration was confirmed in early PWMI lesions by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and a marked depletion of oligodendrocyte progenitors of 71 +/- 8%. Hence, the predilection of preterm infants for PWMI is related to selective lipid peroxidation-mediated injury of cerebral white matter and targeted death of oligodendrocyte progenitors.

  10. Comparison of Oxidative Stress/DNA Damage in Semen and Blood of Fertile and Infertile Men

    PubMed Central

    Guz, Jolanta; Gackowski, Daniel; Foksinski, Marek; Rozalski, Rafal; Zarakowska, Ewelina; Siomek, Agnieszka; Szpila, Anna; Kotzbach, Marcin; Kotzbach, Roman; Olinski, Ryszard

    2013-01-01

    Abnormal spermatozoa frequently display typical features of oxidative stress, i.e. excessive level of reactive oxygen species (ROS) and depleted antioxidant capacity. Moreover, it has been found that a high level of oxidatively damaged DNA is associated with abnormal spermatozoa and male infertility. Therefore, the aim of our study was the comparison of oxidative stress/DNA damage in semen and blood of fertile and infertile men. The broad range of parameters which describe oxidative stress and oxidatively damaged DNA and repair were analyzed in the blood plasma and seminal plasma of groups of fertile and infertile subjects. These parameters include: (i) 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) levels in urine; (ii) 8-oxodG level in DNA isolated from leukocytes and spermatozoa; (iii) antioxidant vitamins (A, C and E) and uric acid. Urinary excretion of 8-oxodG and 8-oxoGua and the level of oxidatively damaged DNA in leukocytes as well as the level of antioxidant vitamins were analyzed using HPLC and HPLC/GC/MS methods. The results of our study demonstrate that 8-oxodG level significantly correlated with every parameter which describe sperm quality: sperm count, motility and morphology. Moreover, the data indicate a higher level of 8-oxodG in sperm DNA compared with DNA of surrogate tissue (leukocytes) in infertile men as well as in healthy control group. For the whole study population the median values of 8-oxodG/106 dG were respectively 7.85 and 5.87 (p = 0.000000002). Since 8-oxodG level in sperm DNA is inversely correlated with urinary excretion rate of 8-oxoGua, which is the product of OGG1 activity, we hypothesize that integrity of spermatozoa DNA may be highly dependent on OGG1 activity. No relationship between the whole body oxidative stress and that of sperm plasma was found, which suggests that the redox status of semen may be rather independent on this characteristic for other tissues. PMID:23874641

  11. Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.

    PubMed Central

    Fraga, C G; Shigenaga, M K; Park, J W; Degan, P; Ames, B N

    1990-01-01

    Oxidative damage to DNA is shown to be extensive and could be a major cause of the physiological changes associated with aging and the degenerative diseases related to aging such as cancer. The oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (oh8dG), one of the approximately 20 known oxidative DNA damage products, has been measured in DNA isolated from various organs of Fischer 344 rats of different ages. oh8dG was present in the DNA isolated from all the organs studied: liver, brain, kidney, intestine, and testes. Steady-state levels of oh8dG ranged from 8 to 73 residues per 10(6) deoxyguanosine residues or 0.2-2.0 x 10(5) residues per cell. Levels of oh8dG in DNA increased with age in liver, kidney, and intestine but remained unchanged in brain and testes. The urinary excretion of oh8dG, which presumably reflects its repair from DNA by nuclease activity, decreased with age from 481 to 165 pmol per kg of body weight per day for urine obtained from 2-month- and 25-month-old rats, respectively. 8-Hydroxyguanine, the proposed repair product of a glycosylase activity, was also assayed in the urine. We estimate approximately 9 x 10(4) oxidative hits to DNA per cell per day in the rat. The results suggest that the age-dependent accumulation of oh8dG residues observed in DNA from liver, kidney, and intestine is principally due to the slow loss of DNA nuclease activity; however, an increase in the rate of oxidative DNA damage cannot be ruled out. PMID:2352934

  12. Oxidative damage of the extracts of condensate, particulate and semivolatile organic compounds from gasoline engine exhausts on testicles of rats.

    PubMed

    Che, Wangjun; Qiu, Hong; Liu, Guiming; Ran, Yun; Zhang, Hao; Zhang, Li; Wen, Weihua

    2009-07-01

    Oxidative damage induced by extracts of condensate, particulate matters and semivolatile organic compounds from gasoline engine exhausts were investigated in testicles of adult Sprague-Dawley rats. The results showed that gasoline engine exhaust could increase the contents of malondialdehyde and carbonyl protein, decrease activities of superoxide dismutase and glutathione peroxidase, and induce DNA damage in testicle of rat. Taking together, the gasoline engine exhaust could promote oxidative damage of bio-macromolecular in testicles of rat and oxidative stress might be an alternative mechanism for male reproductive function of male mammals.

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

    PubMed

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

    1998-04-15

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

  14. Intraneuronal amyloid beta accumulation and oxidative damage to nucleic acids in Alzheimer disease.

    PubMed

    Nunomura, Akihiko; Tamaoki, Toshio; Tanaka, Koich; Motohashi, Nobutaka; Nakamura, Masao; Hayashi, Takaaki; Yamaguchi, Haruyasu; Shimohama, Shun; Lee, Hyoung-gon; Zhu, Xiongwei; Smith, Mark A; Perry, George

    2010-03-01

    In an analysis of amyloid pathology in Alzheimer disease, we used an in situ approach to identify amyloid-beta (Abeta) accumulation and oxidative damage to nucleic acids in postmortem brain tissue of the hippocampal formation from subjects with Alzheimer disease. When carboxyl-terminal-specific antibodies directed against Abeta40 and Abeta42 were used for immunocytochemical analyses, Abeta42 was especially apparent within the neuronal cytoplasm, at sites not detected by the antibody specific to Abeta-oligomer. In comparison to the Abeta42-positive neurons, neurons bearing oxidative damage to nucleic acids were more widely distributed in the hippocampus. Comparative density measurements of the immunoreactivity revealed that levels of intraneuronal Abeta42 were inversely correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized nucleoside (r=- 0.61, p<0.02). Together with recent evidence that the Abeta peptide can act as an antioxidant, these results suggest that intraneuronal accumulation of non-oligomeric Abeta may be a compensatory response in neurons to oxidative stress in Alzheimer disease.

  15. Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress

    PubMed Central

    Martinez, Vicente; Mestre, Teresa C.; Rubio, Francisco; Girones-Vilaplana, Amadeo; Moreno, Diego A.; Mittler, Ron; Rivero, Rosa M.

    2016-01-01

    Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance. PMID:27379130

  16. Free fatty acids enhance the oxidative damage induced by ethanol metabolism in an in vitro model.

    PubMed

    Hernández, Ileana; Domínguez-Pérez, Mayra; Bucio, Leticia; Souza, Verónica; Miranda, Roxana U; Clemens, Dahn L; Gomez-Quiroz, Luis Enrique; Gutiérrez-Ruiz, María Concepción

    2015-02-01

    In recent years, there has been a growing interest to explore the responsiveness to injury in steatotic hepatocyte. VL-17A cells, which express ADH and Cyp2E1 overloaded with free fatty acids (1 mM of oleic and palmitic acid 2:1) showed an increased oxidative damaged after 24 h free fatty acids treatment when exposed to ethanol (100 mM) for 48 h as a second injury. An increment in reactive oxygen species, determined by DCFH-DA, protein oxidation, and apoptosis were observed although an increase in main antioxidant proteins such as superoxide dismutase 1 and glutathione peroxidase were observed, but failed in gamma-glutamylcysteine synthetase, suggesting a decreased capacity of synthesis of glutathione compared with cells treated only with free fatty acids or ethanol. The increased oxidative stress and toxicity in lipid overloaded VL-17A cells subjected to ethanol exposure were accompanied by increases in Cyp2E1 protein expression. Our data show that lipid loaded in an in vitro model, VL-17A cells, is more susceptible to cell damage and oxidative stress when treated with ethanol.

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

    PubMed

    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.

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

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    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. PMID:25608939

  19. Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress.

    PubMed

    Martinez, Vicente; Mestre, Teresa C; Rubio, Francisco; Girones-Vilaplana, Amadeo; Moreno, Diego A; Mittler, Ron; Rivero, Rosa M

    2016-01-01

    Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance.

  20. Induction of ROS Overload by Alantolactone Prompts Oxidative DNA Damage and Apoptosis in Colorectal Cancer Cells.

    PubMed

    Ding, Yushuang; Wang, Hongge; Niu, Jiajing; Luo, Manyu; Gou, Yangmei; Miao, Lining; Zou, Zhihua; Cheng, Ying

    2016-04-14

    Cancer cells typically display higher than normal levels of reactive oxygen species (ROS), which may promote cancer development and progression but may also render the cancer cells more vulnerable to further ROS insult. Indeed, many of the current anticancer therapeutics kill cancer cells via induction of oxidative stress, though they target both cancer and normal cells. Recently, alantolactone (ATL), a natural sesquiterpene lactone, has been shown to induce apoptosis by increasing ROS levels specifically in cancer cells; however, the molecular mechanisms linking ROS overproduction to apoptosis remain unclear. Here we show that the ATL-induced ROS overload in human SW480 and SW1116 colorectal cancer cells was followed by a prominent accumulation of cellular oxidized guanine (8-oxoG) and immediate increase in the number of DNA strand breaks, indicating that increased ROS resulted in extensive oxidative DNA damage. Consequently, the G₁/S-CDK suppresser CDKN1B (p21) and pro-apoptotic proteins Bax and activated caspase-3 were upregulated, while anti-apoptotic Bcl-2 was downregulated, which were followed by cell cycle arrest at G₁ and marked apoptosis in ATL-treated cancer but not non-cancer cells. These results suggest that the ATL-induced ROS overload triggers cell death through induction of massive oxidative DNA damage and subsequent activation of the intrinsic apoptosis pathway.

  1. Neutrophil-generated oxidative stress and protein damage in Staphylococcus aureus.

    PubMed

    Beavers, William N; Skaar, Eric P

    2016-08-01

    Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an infectious agent. During S. aureus colonization and invasion, leukocytes are recruited to the site of infection. To combat S. aureus, leukocytes generate an arsenal of reactive species including superoxide, hydrogen peroxide, nitric oxide and hypohalous acids that modify and inactivate cellular macromolecules, resulting in growth defects or death. When S. aureus colonization cannot be cleared by the immune system, antibiotic treatment is necessary and can be effective. Yet, this organism quickly gains resistance to each new antibiotic it encounters. Therefore, it is in the interest of human health to acquire a deeper understanding of how S. aureus evades killing by the immune system. Advances in this field will have implications for the design of future S. aureus treatments that complement and assist the host immune response. In that regard, this review focuses on how S. aureus avoids host-generated oxidative stress, and discusses the mechanisms used by S. aureus to survive oxidative damage including antioxidants, direct repair of damaged proteins, sensing oxidant stress and transcriptional changes. This review will elucidate areas for studies to identify and validate future antimicrobial targets.

  2. Brain oxidative damage restored by Sesbania grandiflora in cigarette smoke-exposed rats.

    PubMed

    Ramesh, Thiyagarajan; Sureka, Chandrabose; Bhuvana, Shanmugham; Begum, Vavamohaideen Hazeena

    2015-08-01

    Cigarette smoking has been associated with high risk of neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, etc., The present study was designed to evaluate the restorative effects of Sesbania grandiflora (S. grandiflora) on oxidative damage induced by cigarette smoke exposure in the brain of rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day by oral gavage) for a period of 3 weeks. The levels of protein carbonyl, nitric oxide, and activities of cytochrome P450, NADPH oxidase and xanthine oxidase were significantly increased, whereas the levels of total thiol, protein thiol, non-protein thiol, nucleic acids, tissue protein and the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were significantly diminished in the brain of rats exposed to cigarette smoke as compared with control rats. Also cigarette smoke exposure resulted in a significant alteration in brain total lipid, total cholesterol, triglycerides and phospholipids content. Treatment of SGAS is regressed these alterations induced by cigarette smoke. The results of our study suggest that S. grandiflora restores the brain from cigarette smoke induced oxidative damage. S. grandiflora could have rendered protection to the brain by stabilizing their cell membranes and prevented the protein oxidation, probably through its free radical scavenging and anti-peroxidative effect.

  3. Risk of Oxidative Damage to Bone from Increased Iron Stores During Space Flight

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Smith, S. M.

    2014-01-01

    Iron stores are increased secondary to neocytolysis of red blood cells and a high dietary intake of iron during space flight. This raises concerns about the risk of excess iron causing oxidative damage in many tissues, including bone. Biomarkers of iron status, oxidative damage, and bone resorption during space flight were analyzed for 23 (16 M/7 F) International Space Station crewmembers as part of the Nutrition SMO project. Up to 5 in-flight blood samples and 24-h urine pools were collected over the course of the 4-6 month missions. Serum iron increased slightly during space flight and was decreased at landing (P < 0.0004). An increase in serum ferritin early in flight (217% in women and 68% in men, P < 0.0004), returning to preflight concentrations at landing, and a decrease in transferrin and transferrin receptors during flight indicated that a transient increase in iron stores occurred. No inflammatory response was observed during flight. The oxidative damage markers 8-hydroxy-2'-deoxyguanosine and prostaglandin F(sub 2(alpha)) were positively correlated (both P < 0.001) with serum ferritin. A greater area under the curve for ferritin during flight was correlated with greater changes in bone mineral density of several bone regions after flight (1). In a separate study (2), a ground-based investigation was conducted that examined the combined effects of radiation exposure and iron overload on sensitivity to radiation injury in several physiological systems in 12-wk male Sprague-Dawley rats. The rats were acclimated to an adequate iron diet (45 mg iron (ferric citrate)/kg diet) for 3 wk and then assigned to one of four groups: adequate iron (Fe) diet/no radiation, adequate Fe diet/ radiation, moderately high Fe diet (650 mg Fe (ferric citrate)/kg diet)/no radiation, and moderately high Fe diet/radiation. Animals remained on the assigned diet for 4 wk. Starting on day 14 of experimental diet treatment, animals were exposed to a fractionated dose (0.375 Gy) of Cs

  4. Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling.

    PubMed

    Suzuki, Maiko; Bandoski, Cheryl; Bartlett, John D

    2015-12-01

    Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These

  5. Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling

    PubMed Central

    Suzuki, Maiko; Bandoski, Cheryl; Bartlett, John D.

    2015-01-01

    Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These

  6. Oxidative damage to cellular and isolated DNA by metabolites of a fungicide ortho-phenylphenol.

    PubMed

    Murata, M; Moriya, K; Inoue, S; Kawanishi, S

    1999-05-01

    ortho-Phenylphenol (OPP) and its sodium salt, which are used as fungicides and antibacterial agents, have been found to cause carcinomas in the urinary tract of rats. To clarify the carcinogenic mechanism of OPP, we compared the DNA damage inducing ability of an OPP metabolite, phenyl-1,4-benzoquinone (PBQ) with that of another metabolite, phenylhydroquinone (PHQ). Pulsed field gel electrophoresis showed that PBQ and PHQ induced DNA strand breakage in cultured human cells, but PBQ did it more efficiently than PHQ. Significant increases in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) were observed in cells treated with PBQ and PHQ, and the increase of 8-oxodG induced by PBQ was significantly higher than that induced by PHQ. Using 32P-5'-end-labeled DNA fragments obtained from human p53 tumor suppressor gene and c-Ha-ras-1 protooncogene, we showed that PBQ plus NADH, and also PHQ, induced DNA damage frequently at thymine residues, in the presence of Cu(II). The intensity of DNA damage by PBQ was stronger than that by PHQ, showing higher importance of PBQ than other OPP metabolites. Catalase and bathocuproine inhibited Cu(II)-mediated DNA damage by PBQ plus NADH and PHQ, suggesting that H2O2 reacts with Cu(I) to produce active species causing DNA damage. Electron spin resonance and UV-visible spectroscopic studies have demonstrated generation of semiquinone radical and superoxide from the reaction of PBQ with NADH or the Cu(II)-mediated autoxidation of PHQ. The present results suggest that these OPP metabolites cause oxidative DNA damage through H2O2 generation in cells, and the damage may lead to mutation and carcinogenesis. It is concluded that PBQ may play a more important role in the expression of OPP carcinogenicity than other OPP metabolites.

  7. Ceruloplasmin copper induces oxidant damage by a redox process utilizing cell-derived superoxide as reductant

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, C. K.; Fox, P. L.

    1998-01-01

    Oxidative damage by transition metals bound to proteins may be an important pathogenic mechanism. Ceruloplasmin (Cp) is a Cu-containing plasma protein thought to be involved in oxidative modification of lipoproteins. We have previously shown that Cp increased cell-mediated low-density lipoprotein (LDL) oxidation by a process requiring cell-derived superoxide, but the underlying chemical mechanism(s) is (are) unknown. We now show that superoxide reduction of Cp Cu is a critical reaction in cellular LDL oxidation. By bathocuproine disulfonate (BCS) binding and by superoxide utilization, we showed that exogenous superoxide reduces a single Cp Cu atom, the same Cu required for LDL oxidation. The Cu atom remained bound to Cp during the redox cycle. Three avenues of evidence showed that vascular cells reduce Cp Cu by a superoxide-dependent process. The 2-fold higher rate of Cp Cu reduction by smooth muscle cells (SMC) compared to endothelial cells (EC) was consistent with their relative rates of superoxide release. Furthermore, Cp Cu reduction by cells was blocked by Cu,Zn superoxide dismutase (SOD1). Finally, the level of superoxide produced by EC and SMC was sufficient to cause the amount of Cu reduction observed. An important role of Cp Cu reduction in LDL oxidation was suggested by results showing that SOD1 inhibited Cp Cu reduction and LDL oxidation by SMC with equal potency, while tumor necrosis factor-alpha stimulated both processes. In summary, these results show that superoxide is a critical cellular reductant of divalent transition metals involved in oxidation, and that protein-bound Cu is a substrate for this reaction. The role of these mechanisms in oxidative processes in vivo has yet to be defined.

  8. Supplementation with an antioxidant cocktail containing coenzyme Q prevents plasma oxidative damage induced by soccer.

    PubMed

    Tauler, Pedro; Ferrer, Miguel D; Sureda, Antoni; Pujol, Pere; Drobnic, Franchek; Tur, Josep A; Pons, Antoni

    2008-11-01

    The aim of the study was to determine the effects of an antioxidant supplementation, which includes coenzyme Q(10), on plasma and neutrophil oxidative stress and the antioxidant response after a soccer match. Nineteen voluntary male pre-professional footballers were randomly and double-blinded treated with either a multivitamin and mineral supplement (n = 8) or a placebo (n = 11). After the 3 months of supplementation, the sportsmen played a friendly soccer match of 60 min. The 3-month supplementation induced higher plasma ascorbate and coenzyme Q levels when compared to the placebo group. Antioxidant supplementation influenced plasma oxidative stress markers because they were lower in the supplemented group than in the placebo one after the match. The football match induced decreased neutrophil vitamin E levels and catalase and glutathione peroxidase activities but increased glutathione reductase activity. Antioxidant diet supplementation prevented plasma oxidative damage but did not influence the neutrophil response to a football match.

  9. Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats.

    PubMed

    Acar, Abdullah; Akil, Esref; Alp, Harun; Evliyaoglu, Osman; Kibrisli, Erkan; Inal, Ali; Unan, Fatma; Tasdemir, Nebahat

    2012-07-01

    To date, there have not been enough studies about the effects of curcumin against oxidative stress on sciatic nerves caused by streptozotocin (STZ) in diabetic rats. Therefore, this study was undertaken to determine whether curcumin, by virtue of its antioxidant properties, could affect the oxidant/antioxidant balance in the sciatic nerve and brain tissues of streptozotocin (STZ)-induced diabetic rats. A total of 28 rats were randomly divided into four groups of seven rats each: normal controls, only curcumin treated, diabetic controls, and diabetics treated with curcumin. Biomarkers-malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and NO levels-for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. We found a significant increase in MDA, NO, TOS, and OSI, along with a reduction in TAS levels in the brains and sciatic nerves of the STZ-induced diabetic rats (for both parameters p < 0.05). The MDA, TOS, OSI, and NO levels in these tissues were significantly reduced in the curcumin-treated diabetic group compared to the untreated diabetic group. In conclusion, the results of this study suggested that curcumin exhibits neuroprotective effects against oxidative damage in the brain and sciatic tissues of diabetic rats.

  10. Oxidative damage of copper chloride overload to the cultured rat astrocytes.

    PubMed

    Hu, Hao-Lu; Ni, Xiu-Shi; Duff-Canning, Sarah; Wang, Xiao-Ping

    2016-01-01

    Disorders of copper metabolism are associated with neurological dysfunction including Wilson's disease (WD). WD is a autosomal recessive disorder caused by mutations in the ATP7B gene resulting in the inability of the hepatocytes to remove excess copper. Gradual copper accumulation causes damage to liver, brain and other organs manifesting in liver disease, neurological and psychiatric symptoms. Also scond copper-neurometaboic disorder: Menkes disease charaterized with mutated ATP7A gene, is ralated with abnormally neuroal transmission and synaptogenesis. Parkinson's disease and Alzheimer's disease both are refered to some degree of copper/iron metabolism changes. The precise mechanisms by which excess copper causes neurological damage remain to be elucidated. In this study, we aimed to investigate the influence of excessive amounts of Cu(2+) on the oxidative damage response and survival of primary astrocytes from newborn rats. Primary cultured rat astrocytes were divided into three groups: 30 μmol/L CuCl2, 100 μmol/L CuCl2 and control. At 12, 24, 48, 96 and 120 hours of CuCl2 intervention, cell viability, intracellular reduced glutathione level and glutathion reductase activity, and nitric oxide secretion were determined. It was found that 30 μmol/L CuCl2 might stimulate the exaltation and the compensatory proliferation of astrocytes. The survival rate of astrocytes in the 100 μmol/L CuCl2 group was significantly decreased relative to the 30 μmol/L CuCl2 group. At 24 hours of CuCl2 intervention, intracellular reduced glutathione level and glutathion reductase activity were significantly decreased in the 100 μmol/L CuCl2 group compared to the control group. At 120 hours of CuCl2 intervention, nitric oxide secretion in the 100 μmol/L CuCl2 group was significantly greater than in the control group. Under pathological conditions, excessive amounts of Cu(2+) greatly damaged the growth and proliferation of astrocytes, reduced the anti-oxidative capacity of

  11. Oxidative damage of copper chloride overload to the cultured rat astrocytes

    PubMed Central

    Hu, Hao-Lu; Ni, Xiu-Shi; Duff-Canning, Sarah; Wang, Xiao-Ping

    2016-01-01

    Disorders of copper metabolism are associated with neurological dysfunction including Wilson’s disease (WD). WD is a autosomal recessive disorder caused by mutations in the ATP7B gene resulting in the inability of the hepatocytes to remove excess copper. Gradual copper accumulation causes damage to liver, brain and other organs manifesting in liver disease, neurological and psychiatric symptoms. Also scond copper-neurometaboic disorder: Menkes disease charaterized with mutated ATP7A gene, is ralated with abnormally neuroal transmission and synaptogenesis. Parkinson’s disease and Alzheimer’s disease both are refered to some degree of copper/iron metabolism changes. The precise mechanisms by which excess copper causes neurological damage remain to be elucidated. In this study, we aimed to investigate the influence of excessive amounts of Cu2+ on the oxidative damage response and survival of primary astrocytes from newborn rats. Primary cultured rat astrocytes were divided into three groups: 30 μmol/L CuCl2, 100 μmol/L CuCl2 and control. At 12, 24, 48, 96 and 120 hours of CuCl2 intervention, cell viability, intracellular reduced glutathione level and glutathion reductase activity, and nitric oxide secretion were determined. It was found that 30 μmol/L CuCl2 might stimulate the exaltation and the compensatory proliferation of astrocytes. The survival rate of astrocytes in the 100 μmol/L CuCl2 group was significantly decreased relative to the 30 μmol/L CuCl2 group. At 24 hours of CuCl2 intervention, intracellular reduced glutathione level and glutathion reductase activity were significantly decreased in the 100 μmol/L CuCl2 group compared to the control group. At 120 hours of CuCl2 intervention, nitric oxide secretion in the 100 μmol/L CuCl2 group was significantly greater than in the control group. Under pathological conditions, excessive amounts of Cu2+ greatly damaged the growth and proliferation of astrocytes, reduced the anti-oxidative capacity of

  12. Role of inducible nitrogen oxide synthase in benzene-induced oxidative DNA damage in the bone marrow of mice.

    PubMed

    Vestergaard, Sys; Loft, Steffen; Møller, Peter

    2002-03-01

    We investigated the interaction of BZ and lipolysaccharide (LPS), a well-known inflammation-promoting agent, in wild-type and inducible nitrogen oxide synthase (iNOS) knockout mice. BZ generated DNA strand breaks (SB) in the liver of both wild-type and iNOS-deficient mice. In the bone marrow (BM) BZ and LPS generated SB only in wild-type mice. The effects were additive, suggesting that both a redox cycling and an iNOS-dependent pathway may be involved. Formamidopyrimidine DNA glycosylase sensitive sites were elevated by BZ in the BM in both types of mice, whereas endonuclease III sensitive sites were not affected by any treatment. Since BZ is associated with leukemia in humans, it suggests that oxidative DNA base damage rather than SB may be important in the development of leukemia.

  13. In vitro effects of 50 Hz magnetic fields on oxidatively damaged rabbit red blood cells

    SciTech Connect

    Fiorani, M.; Biagiarelli, B.; Vetrano, F.; Guidi, G.; Dacha, M.; Stocchi, V.

    1997-05-01

    The aim of this study was to investigate the effects of 50 Hz magnetic fields on rabbit red blood cells (RBCs) that were exposed simultaneously to the action of an oxygen radical-generating system, Fe(II)/ascorbate. Previous data obtained in the authors` laboratory showed that the exposure of rabbit erythrocytes or reticulocytes to Fe(II)/ascorbate induces hexokinase inactivation, whereas the other glycolytic enzymes do not show any decay. The authors also observed depletion of reduced glutathione (GSH) content with a concomitant intracellular and extracellular increase in oxidized glutathione (GSSG) and a decrease in energy charge. In this work, they investigated whether 50 Hz magnetic fields could influence the intracellular impairments that occur when erythrocytes or reticulocytes are exposed to this oxidant system, namely, inactivation of hexokinase activity, GSH depletion, a change in energy charge, and hemoglobin oxidation. The results obtained indicate that a 0.5 mT magnetic field had no effect on intact RBCs, whereas it increased the damage in an oxidatively stressed erythrocyte system. In fact, exposure of intact erythrocytes incubated with Fe(II)/ascorbate to a 0.5 mT magnetic field induced a significant further decay in hexokinase activity as well as a twofold increase in methemoglobin production compared with RBCs that were exposed to the oxidant system alone. Although further studies will be needed to determine the physiological implications of these data, the results reported in this study demonstrate that the effects of the magnetic fields investigated are able to potentiate the cellular damage induced in vitro by oxidizing agents.

  14. Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats

    PubMed Central

    Al-Awaida, Wajdy; Akash, Muhanad; Aburubaiha, Zaid; Talib, Wamidh H.; Shehadeh, Hayel

    2014-01-01

    Objective(s): One cause of cigarette smoking is oxidative stress that may alter the cellular antioxidant defense system, induce apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. It has been shown that Chinese green tea (CGT) (Lung Chen Tea) has higher antioxidant property than black tea. In this paper, we will explore the preventive effect of CGT on cigarette smoke-induced oxidative damage, apoptosis and tissues inflammation in albino rat model. Materials and Methods: Albino rats were randomly divided into four groups, i.e. sham air (SA), cigarette smoke (CS), CGT 2% plus SA or plus CS. The exposure to smoking was carried out as a single daily dose (1 cigarette/rat) for a period of 90 days using an electronically controlled smoking machine. Sham control albino rats were exposed to air instead of cigarette smoke. Tissues were collected 24 hr after last CS exposure for histology and all enzyme assays. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay. Results: Long-term administration of cigarette smoke altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. All these pathophysiological and biochemical events were significantly improved when the cigarette smoke-exposed albino rats were given CGT infusion as a drink instead of water. Conclusion: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT. PMID:25729541

  15. Oxidative stress induced sperm DNA damage, a possible reason for male infertility

    PubMed Central

    Hosen, Md Bayejid; Islam, Md Rakibul; Begum, Firoza; Kabir, Yearul; Howlader, M Zakir Hossain

    2015-01-01

    Background: Sperm DNA damage is an important factor in the etiology of male infertility. Objective: The aim of the study was to evaluate the association of oxidative stress induced sperm DNA damage with the pathogenesis of male infertility. Materials and Methods: The study comprised a total of 66 subjects, including fertile men (n=25) and infertile men (n=41) matched by age. Seminal malondialdehyde (MDA), phospholipid hydroperoxide (PHP), superoxide dismutase (SOD), total antioxidant status (TAS) and 8-hydroxy-2'-deoxy guanosine (8-OHdG) were estimated by spectrophotometric and ELISA based methods and the association with the sperm parameters was assessed. Results: The percentages of motile and morphologically normal cells were significantly lower (p < 0.001, p <0.001, respectivly) in infertile men. Seminal levels of MDA, PHP and 8-OHdG were significantly higher (p < 0.001, p < 0.001, and p=0. 02, respectively) while the SOD and TAS were significantly lower (p=0. 0003, p< 0.001, respectively) in infertile men. Sperm parameters were negatively correlated with MDA, PHP and 8-OHdG while positively correlated with SOD and TAS. A positive correlation of 8-OHdG with MDA and PHP and a negative correlation with TAS and SOD were also found. Conclusion: These results suggested that oxidative stress induced sperm DNA damage might have a critical effect on the etiology of infertility. Therefore, evaluation of oxidative status, antioxidant defense systems and DNA damage, together with sperm parameters might be a useful tool for diagnosis and treatment of male infertility. PMID:26568756

  16. Comparative toxicity of silver nanoparticles on oxidative stress and DNA damage in the nematode, Caenorhabditis elegans.

    PubMed

    Ahn, Jeong-Min; Eom, Hyun-Jeong; Yang, Xinyu; Meyer, Joel N; Choi, Jinhee

    2014-08-01

    This study examined the effects of polyvinylpyrrolidone (PVP) surface coating and size on the organismal and molecular toxicity of silver nanoparticles (AgNPs) on the nematode, Caenorhabditis elegans. The toxicity of bare AgNPs and 8 and 38 nm PVP-coated AgNPs (PVP8-AgNPs, PVP38-AgNPs) were compared. The toxicity of AgNO3 was also tested because ion dissolution and particle-specific effects are often important characteristics determining Ag nanotoxicity. Comparative toxicity across AgNO3 and the three different types of AgNPs was first evaluated using a C. elegans mortality test by a direct comparison of the LC50 values. Subsequently, mutant screening followed by oxidative stress, mitochondrial toxicity and DNA damage assays were carried out at equitoxic (LC10 and LC50) concentrations to further assess the toxicity mechanism of AgNO3 and AgNPs. AgNO3 and bare AgNPs had similar toxicities, whereas PVP coating reduced the toxicity of the AgNPs significantly. Of the PVP-AgNPs, the smaller NPs were more toxic. Different groups of mutants responded differently to AgNO3 and AgNPs, which indicates that their toxicity mechanism might be different. AgNO3 and bare AgNPs induced mitochondrial membrane damage. None of the silver materials tested caused detectable polymerase-inhibiting DNA lesions in either the nucleus or mitochondria as measured by a quantitative PCR assay, but AgNO3, bare AgNPs and PVP8-AgNPs induced oxidative DNA damage. These results show that coatings on the AgNPs surface and the particle size make a clear contribution to the toxicity of the AgNPs, and oxidative stress-related mitochondrial and DNA damage appear to be potential mechanisms of toxicity.

  17. Eugenol-inhibited root growth in Avena fatua involves ROS-mediated oxidative damage.

    PubMed

    Ahuja, Nitina; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2015-02-01

    Plant essential oils and their constituent monoterpenes are widely known plant growth retardants but their mechanism of action is not well understood. We explored the mechanism of phytotoxicity of eugenol, a monoterpenoid alcohol, proposed as a natural herbicide. Eugenol (100-1000 µM) retarded the germination of Avena fatua and strongly inhibited its root growth compared to the coleoptile growth. We further investigated the underlying physiological and biochemical alterations leading to the root growth inhibition. Eugenol induced the generation of reactive oxygen species (ROS) leading to oxidative stress and membrane damage in the root tissue. ROS generation measured in terms of hydrogen peroxide, superoxide anion and hydroxyl radical content increased significantly in the range of 24 to 144, 21 to 91, 46 to 173% over the control at 100 to 1000 µM eugenol, respectively. The disruption in membrane integrity was indicated by 25 to 125% increase in malondialdehyde (lipid peroxidation byproduct), and decreased conjugated diene content (~10 to 41%). The electrolyte leakage suggesting membrane damage increased both under light as well as dark conditions measured over a period from 0 to 30 h. In defense to the oxidative damage due to eugenol, a significant upregulation in the ROS-scavenging antioxidant enzyme machinery was observed. The activities of superoxide dismutases, catalases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases were elevated by ~1.5 to 2.8, 2 to 4.3, 1.9 to 5.0, 1.4 to 3.9, 2.5 to 5.5 times, respectively, in response to 100 to 1000 µM eugenol. The study concludes that eugenol inhibits early root growth through ROS-mediated oxidative damage, despite an activation of the antioxidant enzyme machinery.

  18. Oxidative DNA damage caused by pulsed discharge with cavitation on the bactericidal function

    NASA Astrophysics Data System (ADS)

    Kudo, Ken-ichi; Ito, Hironori; Ihara, Satoshi; Terato, Hiroaki

    2015-09-01

    Plasma-based techniques are expected to have practical use for wastewater purification with a potential for killing contaminated microorganisms and degrading recalcitrant materials. In the present study, we analysed oxidative DNA damage in bacterial cells treated by the plasma to unveil its mechanisms in the bactericidal process. Escherichia coli cell suspension was exposed to the plasma induced by applying an alternating-current voltage of about 1 kV with bubbling formed by water-cavitation, termed pulsed discharge with cavitation. Chromosomal DNA damage, such as double strand break (DSB) and oxidative base lesions, increased proportionally with the applied energy, as determined by electrophoretic and mass spectrometric analyses. Among the base lesions identified, the yields of 8-hydroxyguanine (8-OH-G) and 5-hydroxycytosine (5-OH-C) in chromosomal DNA increased by up to 4- and 15-fold, respectively, compared to untreated samples. The progeny DNA sequences, derived from plasmid DNA exposed to the plasma, indicated that the production rate of 5-OH-C exceeded that of 8-OH-G, as G:C to A:T transitions accounted for 65% of all base changes, but only a few G:C to T:A transversions were observed. The cell viabilities of E. coli cells decreased in direct proportion to increases in the applied energy. Therefore, the plasma-induced bactericidal mechanism appears to relate to oxidative damage caused to bacterial DNA. These results were confirmed by observing the generation of hydroxyl radicals and hydrogen peroxide molecules following the plasma exposure. We also compared our results with the plasma to those obtained with 137Cs γ-rays, as a well-known ROS generator to confirm the DNA-damaging mechanism involved.

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

    PubMed

    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). In chronic hypoxia group, MDA level was significantly higher than that in the control group (P < 0.05), whereas SOD level had no significant difference between the two groups (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.

  20. The Anti-Oxidative Role of Micro-Vesicles Derived from Human Wharton-Jelly Mesenchymal Stromal Cells through NOX2/gp91(phox) Suppression in Alleviating Renal Ischemia-Reperfusion Injury in Rats

    PubMed Central

    Miao, Shuai; Chen, Jinjun; Du, Tao; Zhong, Liang; Ju, Guanqun; Liu, Guohua; Zhu, Yingjian

    2014-01-01

    Oxidative stress is known as one of the main contributors in renal ischemia/reperfusion injury (IRI). Here we hypothesized that Micro-vesicles (MVs) derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs) could protect kidney against IRI through mitigating oxidative stress. MVs isolated from hWJMSCs conditioned medium were injected intravenously in rats immediately after unilateral kidney ischemia for 60 min. The animals were sacrificed at 24h, 48h and 2 weeks respectively after reperfusion. Our results show that the expression of NOX2 and reactive oxygen species (ROS) in injured kidney tissues was declined and the oxidative stress was alleviated in MVs group at 24h and 48h in parallel with the reduced apoptosis and enhanced proliferation of cells. IRI-initiated fibrosis was abrogated by MVs coincident with renal function amelioration at 2 weeks. NOX2 was also found down-regulated by MVs both in human umbilical vein endothelial cells (HUVEC) and NRK-52E cell line under hypoxia injury model in vitro. In conclusion, a single administration of hWJMSC-MVs might protect the kidney by alleviation of the oxidative stress in the early stage of kidney IRI through suppressing NOX2 expression. Moreover, it could reduce the fibrosis and improved renal function. PMID:24637475

  1. Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats.

    PubMed

    Ishizuka, Toshiaki; Niwa, Atsuko; Tabuchi, Masaki; Ooshima, Kana; Higashino, Hideaki

    2008-03-26

    Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.

  2. Oxidative Stress and DNA Damage Induced by Chromium in Liver and Kidney of Goldfish, Carassius auratus

    PubMed Central

    Velma, Venkatramreddy; Tchounwou, Paul B.

    2013-01-01

    Chromium (Cr) is an abundant element in the Earth’s crust. It exhibits various oxidation states, from divalent to hexavalent forms. Cr has diverse applications in various industrial processes and inadequate treatment of the industrial effluents leads to the contamination of the surrounding water resources. Hexavalent chromium (Cr (VI)) is the most toxic form, and its toxicity has been associated with oxidative stress. The present study was designed to investigate the toxic potential of Cr (VI) in fish. In this research, we investigated the role of oxidative stress in chromium-induced genotoxicity in the liver and kidney cells of goldfish, Carassius auratus. Goldfish were acclimatized to the laboratory conditions and exposed them to 5% and 10% of 96 hr-LC50 (85.7 mg/L) of aqueous Cr (VI) in a continuous flow through system. Fish were sampled every 7 days for a period of 28 days to analyze the lipid hydroperoxides (LHP) levels and genotoxic potentials in the liver and kidney. LHP levels were analyzed by spectrophotometry while genotoxicity was assessed by single cell gel electrophoresis (comet) assay. LHP levels in the liver increased significantly at week 1, followed by a decrease. LHP levels in the kidney increased significantly at weeks 1, 2, and 3, and decreased at week 4 compared to the control. The percentage of DNA damage increased in both liver and kidney at both test concentrations. The results clearly indicate that Cr (VI) induces significant levels of DNA damage in liver and kidney cells of goldfish. The induced LHP levels in both organs were concentration-dependent and were directly correlated with the levels of DNA damage. The two tested Cr (VI) concentrations induced significant levels of oxidative stress in both organs, however the kidney appears to be more vulnerable and sensitive to Cr-induced toxicity than the liver. PMID:23700361

  3. Zn(II)-curcumin protects against oxidative stress, deleterious changes in sperm parameters and histological alterations in a male mouse model of cyclophosphamide-induced reproductive damage.

    PubMed

    Lu, Wen-Ping; Mei, Xue-Ting; Wang, Yu; Zheng, Yan-Ping; Xue, Yun-Fei; Xu, Dong-Hui

    2015-03-01

    The poor bioavailability and stability of curcumin limit its clinical application. A novel Zn(II)-curcumin complex was synthesized and its effects against cyclophosphamide (CP)-induced reproductive damage were compared with curcumin. Oral administration of Zn(II)-curcumin significantly prevented CP-induced elevation of malondialdehyde (MDA) level and reductions in superoxide dismutase (SOD) activity and glutathione (GSH) content in mouse testis. Zn(II)-curcumin significantly ameliorated CP-induced reductions in body and reproductive organs weights. Zn(II)-curcumin dose-dependently ameliorated CP-induced reproductive system impairments, by improving sperm parameters (sperm count, viability, motility) and reducing serum testosterone and histological alterations. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively alleviated CP-induced reproductive injury, leading to a reduced severity of testicular pathologic changes, lower MDA level, elevated SOD activity and GSH content, and increased sperm parameters and serum testosterone. These results suggest Zn(II)-curcumin more effectively protects against CP-induced reproductive damage than curcumin alone due to a synergistic reduction in oxidative stress.

  4. Different mechanisms between copper and iron in catecholamines-mediated oxidative DNA damage and disruption of gene expression in vitro.

    PubMed

    Nishino, Yoshihiko; Ando, Motozumi; Makino, Rena; Ueda, Koji; Okamoto, Yoshinori; Kojima, Nakao

    2011-07-01

    Catechols produce reactive oxygen species (ROS) and induce oxidative DNA damage through reduction-oxidation reactions with metals such as copper. Here, we examined oxidative DNA damage by neurotransmitter catecholamines in the presence of copper or iron and evaluated the effects of this damage on gene expression in vitro. Dopamine induced strand breaks and base oxidation in calf thymus DNA in the presence of Cu(II) or Fe(III)-NTA (nitrilotriacetic acid). The extent of this damage was greater for Cu(II) than for Fe(III)-NTA. For the DNA damage induced by dopamine, the responsible reactive species were hydrogen peroxide and Cu(I) for Cu(II) and hydroxyl radicals and Fe(II) for Fe(III)-NTA. Cu(II) induced DNA conformational changes, but Fe(III)-NTA did not in the presence of dopamine. These differences indicate different modes of action between Cu and Fe-NTA with regard to the induction of DNA damage. Expression of the lacZ gene coded on plasmid DNA was inhibited depending on the extent of the oxidative damage and strand breaks. Endogenous catecholamines (dopamine, adrenaline, and noradrenaline) were more potent than catechols (no aminoalkyl side chains) or 3,4-dihydroxybenzylamine (aminomethyl side chain). These results suggest that the metal-mediated DNA damage induced by dopamine disrupts gene expression, and leukoaminochromes (further oxidation products of O-quinones having aminoethyl side chain) are involved in the DNA damage. These findings indicate a possibility that metal (especially iron and copper)-mediated oxidation of catecholamines plays an important role in the pathogenesis of neurodegenerative disorders including Parkinson's disease.

  5. Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.

    PubMed

    Wei, Na; Shi, Yi; Truong, Lan N; Fisch, Kathleen M; Xu, Tao; Gardiner, Elisabeth; Fu, Guangsen; Hsu, Yun-Shiuan Olivia; Kishi, Shuji; Su, Andrew I; Wu, Xiaohua; Yang, Xiang-Lei

    2014-10-23

    Tyrosyl-tRNA synthetase (TyrRS) is known for its essential aminoacylation function in protein synthesis. Here we report a function for TyrRS in DNA damage protection. We found that oxidative stress, which often downregulates protein synthesis, induces TyrRS to rapidly translocate from the cytosol to the nucleus. We also found that angiogenin mediates or potentiates this stress-induced translocalization. The nuclear-localized TyrRS activates transcription factor E2F1 to upregulate the expression of DNA damage repair genes such as BRCA1 and RAD51. The activation is achieved through direct interaction of TyrRS with TRIM28 to sequester this vertebrate-specific epigenetic repressor and its associated HDAC1 from deacetylating and suppressing E2F1. Remarkably, overexpression of TyrRS strongly protects against UV-induced DNA double-strand breaks in zebrafish, whereas restricting TyrRS nuclear entry completely abolishes the protection. Therefore, oxidative stress triggers an essential cytoplasmic enzyme used for protein synthesis to translocate to the nucleus to protect against DNA damage.

  6. Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress.

    PubMed

    Kim, Ki Cheon; Piao, Mei Jing; Madduma Hewage, Susara Ruwan Kumara; Han, Xia; Kang, Kyoung Ah; Jo, Jin Oh; Mok, Young Sun; Shin, Jennifer H; Park, Yeunsoo; Yoo, Suk Jae; Hyun, Jin Won

    2016-01-01

    The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, th