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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. Effects of montmorillonite on alleviating dietary Cd-induced oxidative damage in carp (Carassius auratus).

    PubMed

    Kim, Song Gwan; Dai, Wei; Xu, Zirong; Li, Guanghuan

    2011-06-01

    The present study was designed to investigate the effects of montmorillonite (MMT) on dietary Cd-induced oxidative damage in liver and kidney of carp (Carassius auratus). One hundred eighty carp were randomly divided into four groups and fed with a basal diet, a basal diet supplemented with 0.5% MMT, Cd-comtaminated basal diet (120 mg Cd/kg dry weight) and Cd-contaminated basal diet supplemented with 0.5% MMT, respectively. After 60 days, fish were sacrificed to measure malondialdehyde (MDA) content and antioxidative indices in liver and kidney. The results showed that the exposure of carp to dietary Cd caused decreases in glutathione peroxidase activity, catalase activity, superoxide dismutase activity, glutathione content and total antioxidant capacity level, while MMT supplemented in diet compensated Cd-induced decreases in above antioxidant indices to some extent in liver and kidney. As compared with the control group, increases in MDA content were observed in both measured tissues of carp exposed to dietary Cd, while MDA content decreased in carp exposed to Cd-contaminated basal diet supplemented with MMT in comparison with the Cd-contaminated group. It was suggested that MMT, when co-administered with Cd in diet, could alleviate dietary Cd-induced oxidative damage in liver and kidney of carp.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  9. Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage.

    PubMed

    Salem, Ahmed M; Mohammaden, Tarek F; Ali, Mohamed A M; Mohamed, Enas A; Hassan, Hesham F

    2016-09-01

    Ionizing radiation interacts with biological systems through the generation of free radicals, which induce oxidative stress. Aluminium (Al) can negatively impact human health by direct interaction with antioxidant enzymes. Ellagic acid (EA) and Ferulic acid (FA) are plant polyphenolic compounds, have gained attention due to their multiple biological activities. To date, no studies investigating the antioxidant effect of EA/FA in a model involving both γ radiation and aluminium chloride (AlCl3) have been reported. Herein, we investigated the protective effect of EA and FA against oxidative stress induced by γ radiation and AlCl3 in rats. Rats were divided into thirteen groups: a negative control group, 3 positive control groups (γ-irradiated, AlCl3-treated and γ-irradiated+AlCl3-treated) and 9 groups (3 γ-irradiated, 3 AlCl3-treated and 3 γ-irradiated+AlCl3-treated) treated with EA and/or FA. Liver function and lipid profile were assessed. Levels of lipid peroxidation, protein oxidation and endogenous antioxidants as well as the concentrations of copper, iron and zinc were estimated in liver tissue homogenate. Furthermore, liver tissue sections were histologically examined. Oral administration of EA and/or FA resulted in 1) amelioration of AlCl3 and/or γ-radiation-induced hepatic function impairment, dyslipidemia and hepatic histological alterations; 2) reduction in liver MDA and PCC levels; 3) elevation of liver CAT, GPx and SOD activity as well as GSH level; 4) elevation in liver Cu concentrations which was accompanied by a reduction in Fe and Zn concentrations. Oral administration of EA and/or FA may be useful for ameliorating γ radiation and/or AlCl3-induced oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. 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.

  11. Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy.

    PubMed

    Yerra, Veera Ganesh; Kalvala, Anil Kumar; Kumar, Ashutosh

    2017-09-01

    Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells. Diabetic rats and high glucose-exposed N2A cells showed reduction in SIRT1 expression with consequent decline in mitochondrial biogenesis and autophagy. ILQ (10 & 20 mg/kg, po) administration to diabetic rats for 2 weeks and exposure to glucose-insulted N2A cells resulted in significant SIRT1 activation with concurrent increase in mitochondrial biogenesis and autophagy. ILQ administration also enhanced NAD(+)/NADH ratio in peripheral sciatic nerves which explains its possible SIRT1 modulatory effect. Functional and behavioural studies show beneficial effect of ILQ as it alleviated nerve conduction and nerve blood flow deficits in diabetic rats along with improvement in behavioural parameters (hyperalgesia and allodynia). ILQ treatment to N2A cells reduced high glucose-driven ROS production and mitochondrial membrane depolarization. Further, ILQ-mediated SIRT1 activation facilitated the Nrf2-directed antioxidant signalling. Overall, results from this study suggest that SIRT1 activation by ILQ mimic effects of calorie restriction, that is, PGC-1α-mediated mitochondrial biogenesis, FOXO3a mediated stress resistance and AMPK mediated autophagy effects to counteract the multiple manifestations in experimental DN. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Photoprotection regulated by phosphorus application can improve photosynthetic performance and alleviate oxidative damage in dwarf bamboo subjected to water stress.

    PubMed

    Liu, Chenggang; Wang, Yanjie; Jin, Yanqiang; Pan, Kaiwen; Zhou, Xingmei; Li, Na

    2017-09-01

    Water and nutrients, particularly phosphorus (P), are the two most limiting factors for dwarf bamboo growth in tropical and subtropical areas. Dwarf bamboo is highly sensitive to water stress and often causes severe P deficiency in its growing soils due to the characteristics of shallower roots and expeditious growth. However, little is known about its photoprotective response to soil water deficit and the underlying mechanisms regulated by P application. In this study, a completely randomized design with two factors of two water regimes (well-watered and water-stressed) and two P levels (with and without P application) was arranged to investigate this issue in dwarf bamboo (Fargesia rufa) plants. Water stress not only decreased water status and photochemical activity but also increased lipid peroxidation due to reactive oxygen species (ROS) accumulation irrespective of P application. In this case, thermal dissipation and antioxidative defense were promoted. Moreover, the role of the water-water cycle under this stress still could not be ignored because it accounted for a large proportion of total energy (JPSII). P application significantly enhanced photochemical activity accompanied by increased chlorophyll content in water-stressed plants. Meanwhile, P application remarkably reduced thermal dissipation and hardly affected photorespiration and the water-water cycle under water stress. Although P application only enhanced ascorbate (AsA) level, ROS, particularly hydrogen peroxide (H2O2), and lipid peroxidation were significantly reduced in water-stressed plants. Therefore, P application can improve the photosynthetic capacity by regulating the redistribution of energy absorbed by PSII antennae and independently activating of the H2O2-scavenging function of AsA to alleviate oxidative damage in F. rufa plants, thereby improving their survival under water stress conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Melatonin Alleviates Intracerebral Hemorrhage-Induced Secondary Brain Injury in Rats via Suppressing Apoptosis, Inflammation, Oxidative Stress, DNA Damage, and Mitochondria Injury.

    PubMed

    Wang, Zhong; Zhou, Feng; Dou, Yang; Tian, Xiaodi; Liu, Chenglin; Li, Haiying; Shen, Haitao; Chen, Gang

    2017-08-01

    Intracerebral hemorrhage (ICH) is a cerebrovascular disease with high mortality and morbidity, and the effective treatment is still lacking. We designed this study to investigate the therapeutic effects and mechanisms of melatonin on the secondary brain injury (SBI) after ICH. An in vivo ICH model was induced via autologous whole blood injection into the right basal ganglia in Sprague-Dawley (SD) rats. Primary rat cortical neurons were treated with oxygen hemoglobin (OxyHb) as an in vitro ICH model. The results of the in vivo study showed that melatonin alleviated severe brain edema and behavior disorders induced by ICH. Indicators of blood-brain barrier (BBB) integrity, DNA damage, inflammation, oxidative stress, apoptosis, and mitochondria damage showed a significant increase after ICH, while melatonin reduced their levels. Meanwhile, melatonin promoted further increasing of expression levels of antioxidant indicators induced by ICH. Microscopically, TUNEL and Nissl staining showed that melatonin reduced the numbers of ICH-induced apoptotic cells. Inflammation and DNA damage indicators exhibited an identical pattern compared to those above. Additionally, the in vitro study demonstrated that melatonin reduced the apoptotic neurons induced by OxyHb and protected the mitochondrial membrane potential. Collectively, our investigation showed that melatonin ameliorated ICH-induced SBI by impacting apoptosis, inflammation, oxidative stress, DNA damage, brain edema, and BBB damage and reducing mitochondrial membrane permeability transition pore opening, and melatonin may be a potential therapeutic agent of ICH.

  14. 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.

  15. 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.

  16. 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.

  17. NO accumulation alleviates H2 O2 -dependent oxidative damage induced by Ca(NO3 )2 stress in the leaves of pumpkin-grafted cucumber seedlings.

    PubMed

    Li, Lin; Shu, Sheng; Xu, Qing; An, Ya-Hong; Sun, Jin; Guo, Shi-Rong

    2017-05-01

    Nitric oxide (NO) and hydrogen peroxide (H2 O2 ), two important signaling molecules, are stimulated in plants by abiotic stresses. In this study, we investigated the role of NO and its interplay with H2 O2 in the response of self-grafted (S-G) and salt-tolerant pumpkin-grafted (Cucurbita maxima × C. moschata) cucumber seedlings to 80 mM Ca(NO3 )2 stress. Endogenous NO and H2 O2 production in S-G seedlings increased in a time-dependent manner, reaching maximum levels after 24 h of Ca(NO3 )2 stress. In contrast, a transient increase in NO production, accompanied by H2 O2 accumulation, was observed at 2 h in rootstock-grafted plants. N(w) -Nitro-l-Arg methyl ester hydrochloride (l-NAME), an inhibitor of nitric oxide synthase (NOS), tungstate, an inhibitor of nitrate reductase (NR), and 2-(4-carboxyphenyl)-4,4,5,5-tetramethy-limidazoline-1-oxyl-3-oxide (cPTIO), a scavenger of NO, were found to significantly inhibit NO accumulation induced by salt stress in rootstock-grafted seedlings. H2 O2 production was unaffected by these stress conditions. Ca(NO3 )2 stress-induced NO accumulation was blocked by pretreatment with an H2 O2 scavenger (dimethylthiourea, DMTU) and an inhibitor of NADPH oxidase (diphenyleneiodonium, DPI). In addition, maximum quantum yield of PSII (Fv/Fm), as well as the activities and transcript levels of antioxidant enzymes, were significantly decreased by salt stress in rootstock grafted seedlings after pretreatment with these above inhibitors; antioxidant enzyme transcript levels and activities were higher in rootstock-grafted seedlings compared with S-G seedlings. These results suggest that rootstock grafting could alleviate the oxidative damage induced by Ca(NO3 )2 stress in cucumber seedlings, an effect that may be attributable to the involvement of NO in H2 O2 -dependent antioxidative metabolism. © 2016 Scandinavian Plant Physiology Society.

  18. Exogenous sodium nitroprusside and glutathione alleviate copper toxicity by reducing copper uptake and oxidative damage in rice (Oryza sativa L.) seedlings.

    PubMed

    Mostofa, Mohammad Golam; Seraj, Zeba Islam; Fujita, Masayuki

    2014-11-01

    Nitric oxide (NO) and glutathione (GSH) regulate a variety of physiological processes and stress responses; however, their involvement in mitigating Cu toxicity in plants has not been extensively studied. This study investigated the interactive effect of exogenous sodium nitroprusside (SNP) and GSH on Cu homeostasis and Cu-induced oxidative damage in rice seedlings. Hydroponically grown 12-day-old seedlings were subjected to 100 μM CuSO4 alone and in combination with 200 μM SNP (an NO donor) and 200 μM GSH. Cu exposure for 48 h resulted in toxicity symptoms such as stunted growth, chlorosis, and rolling in leaves. Cu toxicity was also manifested by a sharp increase in lipoxygenase (LOX) activity, lipid peroxidation (MDA), hydrogen peroxide (H2O2), proline (Pro) content, and rapid reductions in biomass, chlorophyll (Chl), and relative water content (RWC). Cu-caused oxidative stress was evident by overaccumulation of reactive oxygen species (ROS; superoxide (O2 (•-)) and H2O2). Ascorbate (AsA) content decreased while GSH and phytochelatin (PC) content increased significantly in Cu-stressed seedlings. Exogenous SNP, GSH, or SNP + GSH decreased toxicity symptoms and diminished a Cu-induced increase in LOX activity, O2 (•-), H2O2, MDA, and Pro content. They also counteracted a Cu-induced increase in superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR), and glyoxalase I and glyoxalase II activities, which paralleled changes in ROS and MDA levels. These seedlings also showed a significant increase in catalase (CAT), glutathione peroxidase (GPX), dehydroascorbate reductase (DHAR), glutathione S-transferase (GST) activities, and AsA and PC content compared with the seedlings stressed with Cu alone. Cu analysis revealed that SNP and GSH restricted the accumulation of Cu in the roots and leaves of Cu-stressed seedlings. Our results suggest that Cu exposure provoked an oxidative burden while

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

    PubMed

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

    2015-12-01

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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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. © 2014 Scandinavian Plant Physiology Society.

  6. 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

  7. Genistein alleviates testicular ischemia and reperfusion injury-induced spermatogenic damage and oxidative stress by suppressing abnormal testicular matrix metalloproteinase system via the Notch 2/Jagged 1/Hes-1 and caspase-8 pathways.

    PubMed

    Al-Maghrebi, M; Renno, W M

    2016-02-01

    The aim of the study is to examine the role of matrix metalloproteinases (MMPs) and their inhibitors (TIMP) during testicular ischemia/reperfusion (t I/R). The involvement of the Notch pathway, and their modulation by the antioxidant genistein is also studied. Three groups of male Sprague-Dawley rats were used: sham rats, t I/R rats, and genistein-treated rats (10 mg/kg). The t I/R rat model underwent testicular artery occlusion of the left testis and was subjected to 60 min ischemia followed by 4 h reperfusion. Protein expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured in testicular tissue. Histological examination was performed to assess spermatogenesis. Protein levels of Notch 2, Jagged 1, and hairy/enhancer of split 1 (hes-1) was quantified. The degree of testicular oxidative stress, DNA damage and germ cell apoptosis were also evaluated. T I/R induced severe tubular damage, a significant increase in MMP- 2 and MMP-9 expression and decreased expression TIMP-1 and TIMP-2. Genistein treatment normalized the MMP-TIMP imbalance. Rats subjected to t I/R had low total antioxidant capacity of the testis, decreased superoxide dismutase activity, and increased oxidative DNA damage. Enhanced activities of caspase 8, caspase 3 and PARP were also observed during t I/R. Genistein reversed the t I/R-induced suppression of the Notch 2/Jagged 1/hes-1 pathway. Genistein was also able to salvage the testicular structure and function through restoring the MMP-TIMP anti-proteolytic balance, suppressing spermatogenic damage, alleviating oxidative stress and apoptosis. The Notch pathway is partly involved in inhibiting the t I/R-induced testicular impairment.

  8. 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.

  9. 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

  10. 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.

  11. Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant and anti-inflammation activities and inhibiting apoptosis pathway.

    PubMed

    Peng, Zhengwu; Wang, Shiquan; Chen, Guanjie; Cai, Min; Liu, Rui; Deng, Jiao; Liu, Jiangzheng; Zhang, Tao; Tan, Qingrong; Hai, Chunxu

    2015-04-01

    Gastrodin (GAS), an active constituent of the Chinese herbal medicine Tianma, has anti-oxidant and anti-inflammation activities but its protective effect to the prevention of neurotoxicity induced by ischemic stroke is unclear. In the present study, middle cerebral artery occlusion (MCAO) was used to establish a mice ischemic stroke model. Infarct volume ratio and neurobehavioral score were evaluated, Nissl staining was performed and the expression of cleaved Caspase 3, Bax and B cell lymphoma 2 (Bcl-2) were assessed at 24 h or 7 days after reperfusion. In addition, the total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, as well as the expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), SOD1, phospho-Akt and total Akt and TNF-α and IL-1β in the ischemic hemispheres were also observed at 6 h after reperfusion to assess oxidative stress and inflammatory changes after GAS treatment. It was found that GAS, especially at high dose (100 mg/kg) reduced tested neuronal injury and neurobehavioral deficient in MCAO mice. Enhanced expression of cleaved Caspase 3 and Bax and decreased expression of Bcl-2 by MCAO were also reversed by GAS. Moreover, GAS treatment decreased the MDA content and the expression of TNF-α and IL-1β, and increased amount of SOD activity and the expression of HO-1 and SOD1 in GAS-treated ischemic brain. Furthermore, GAS significantly increased Akt phosphorylation and Nrf2 expression. These results support the neuroprotective effects of GAS, and the activation of Akt/Nrf2 pathway may play a critical role in the pharmacological action of GAS.

  12. Alleviation of Aflatoxin B1-Induced Genomic Damage by Proanthocyanidins via Modulation of DNA Repair.

    PubMed

    Bakheet, Saleh A; Alhuraishi, Ahmed M; Al-Harbi, Naif O; Al-Hosaini, Khaled A; Al-Sharary, Shakir D; Attia, Mohammed M; Alhoshani, Ali R; Al-Shabanah, Othman A; Al-Harbi, Mohammed M; Imam, Faisal; Ahmad, Sheikh F; Attia, Sabry M

    2016-11-01

    In order to study the mechanisms underlying the alleviation of aflatoxin B1-induced genomic damage by proanthocyanidins (PAs), we examined the modulation of oxidative DNA damage induced by aflatoxin B1 in PAs-pretreated animals. The effects of PAs on changes in the expression of DNA damage and repair genes induced by aflatoxin B1 were also evaluated in rat marrow cells. Administration of PAs before aflatoxin B1 significantly mitigated aflatoxin B1-induced oxidative DNA damage in a dose-dependent manner. Aflatoxin B1 treatment induced significant alterations in the expression of specific DNA repair genes, and the pre-treatment of rats with PAs ameliorated the altered expression of these genes. Conclusively, PAs protect against aflatoxin B1-induced oxidative DNA damage in rats. These protective effects are attributed to the antioxidant effects of PA and enhanced DNA repair through modulation of DNA repair gene expression. Therefore, PAs are a promising chemoprotective agent for averting genotoxic risks associated with aflatoxin B1 exposure.

  13. Effects of Funnelliformis mosseae inoculation on alleviating atrazine damage in Canna indica L. var. flava Roxb.

    PubMed

    Dong, Jing; Wang, Li; Ma, Fang; Yang, Jixian; Zhang, Xue; Zhao, Ting; Qi, Shanshan

    2017-01-02

    Atrazine residue in the environment continually damages plants and therefore requires immediate attention and effective development of methods for its decontamination. The effects of Funnelliformis mosseae inoculation on growth and physiology in atrazine-treated Canna indica L. var. flava Roxb. were investigated. At atrazine concentrations up to 15 mg L(-1), the growth of C. indica plants were negatively affected. Inoculation with F. mosseae alleviated the atrazine inhibition of plant growth and biomass. Furthermore, the chlorophyll content and root function increased under F. mosseae inoculation, and the oxidative stress of malondialdehyde, peroxidase, and superoxide dismutase activities induced by atrazine were also alleviated by F. mosseae inoculation. The removal rate of atrazine by untreated C. indica was significant, with removal rates of 20.5-55.3% by the end of a 14-day experiment; however, F. mosseae inoculation increased the removal rate to 35.6-75.1%. In conclusion, F. mosseae inoculation can alleviate the damage induced by atrazine in C. indica. Accordingly, C. indica inoculated with F. mosseae has excellent potential to be used in phytoremediation in habitats polluted by high atrazine concentrations.

  14. Partial alleviation of oxidative stress induced by gamma irradiation in Vigna radiata by polyamine treatment.

    PubMed

    Sengupta, Mandar; Raychaudhuri, Sarmistha Sen

    2017-08-01

    Environmental changes generate free radicals and reactive oxygen species (ROS) resulting in abiotic stress in plants. This causes alterations in germination, morphology, growth and development ultimately leading to yield loss. Gamma irradiation was used to experimentally induce oxidative damage in an important pulse crop Vigna radiata (L.) Wilczek or mung bean. Our research was aimed towards augmentation of oxidative stress tolerance through treatment with a group of aliphatic amines known as polyamines. We used sub-lethal doses of gamma irradiation to generate oxidative damage which was evaluated using Nitro blue tetrazolium (NBT) staining, total antioxidant activity, 1, 1-Diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assay, proline content and lipid peroxidation. Changes in internal free polyamines and messenger ribonucleic acid (mRNA) expression of key rate-limiting S-adenosylmethionine decarboxylase (SAMDC) enzyme in polyamine biosynthetic pathway was studied using real-time polymerase chain reaction (PCR). We observed increased oxidative damage with higher irradiation dose which was partially alleviated by putrescine treatment. Internal levels of putrescine and spermidine increased with 1 mM (50 and 100 Gy) and 2 mM putrescine treatment. Expression of SAMDC also increased with putrescine treatment. This study shows that treatment with putrescine can partially alleviate oxidative damage caused by gamma rays.

  15. Chronic heart damage following doxorubicin treatment is alleviated by lovastatin.

    PubMed

    Henninger, Christian; Huelsenbeck, Stefanie; Wenzel, Philip; Brand, Moritz; Huelsenbeck, Johannes; Schad, Arno; Fritz, Gerhard

    2015-01-01

    The anticancer efficacy of anthracyclines is limited by cumulative dose-dependent early and delayed cardiotoxicity resulting in congestive heart failure. Mechanisms responsible for anthracycline-induced heart damage are controversially discussed and effective preventive measures are preferable. Here, we analyzed the influence of the lipid lowering drug lovastatin on anthracycline-induced late cardiotoxicity three month after treatment of C57BL/6 mice with five low doses of doxorubicin (5×3mg/kg BW; i.p.). Doxorubicin increased the cardiac mRNA levels of BNP, IL-6 and CTGF, while the expression of ANP remained unchanged. Lovastatin counteracted these persisting cardiac stress responses evoked by the anthracycline. Doxorubicin-induced fibrotic alterations were neither detected by histochemical collagen staining of heart sections nor by analysis of the mRNA expression of collagens. Extensive qRT-PCR-array based analyses revealed a large increase in the mRNA level of heat shock protein Hspa1b in doxorubicin-treated mice, which was mitigated by lovastatin co-treatment. Electron microscopy together with qPCR-based analysis of mitochondrial DNA content indicate that lovastatin attenuates doxorubicin-stimulated hyperproliferation of mitochondria. This was not paralleled by increased expression of oxidative stress responsive genes or senescence-associated proteins. Echocardiographic analyses disclosed that lovastatin protects from the doxorubicin-induced decrease in the left ventricular posterior wall diameter (LVPWD), while constrictions in fractional shortening (FS) and ejection fraction (EF) evoked by doxorubicin were not amended by the statin. Taken together, the data suggest beneficial effects of lovastatin against doxorubicin-induced delayed cardiotoxicity. Clinical studies are preferable to scrutinize the usefulness of statins for the prevention of anthracycline-induced late cardiotoxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet

    PubMed Central

    Pan, Qing-Rong; Ren, Yan-Long; Zhu, Jia-Jia; Hu, Yan-Jin; Zheng, Jin-Su; Fan, Hui; Xu, Yuan; Wang, Guang; Liu, Wen-Xian

    2014-01-01

    Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression. PMID:25025298

  4. 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.

  5. 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.

  6. 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.

  7. Method for alleviating thermal stress damage in laminates. [metal matrix composites

    NASA Technical Reports Server (NTRS)

    Hoffman, C. A.; Weeton, J. W.; Orth, N. W. (Inventor)

    1980-01-01

    A method is provided for alleviating the stress damage in metallic matrix composites, such as laminated sheet or foil composites. Discontinuities are positively introduced into the interface between the layers so as to reduce the thermal stress produced by unequal expansion of the materials making up the composite. Although a number of discrete elements could be used to form one of the layers and thus carry out this purpose, the discontinuities are preferably produced by simply drilling holes in the metallic matrix layer or by forming grooves in a grid pattern in this layer.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Gilaburu (Viburnum opulus L.) fruit extract alleviates testis and sperm damages induced by taxane-based chemotherapeutics.

    PubMed

    Sarıözkan, Serpil; Türk, Gaffari; Eken, Ayşe; Bayram, Latife Çakır; Baldemir, Ayşe; Doğan, Gülden

    2017-09-18

    In this study, it was aimed to investigate the possible protective effects of gilaburu (Viburnum opulus L., Glb) fruit extract on testis and sperm damages induced by docetaxel (DTX) and paclitaxel (PTX) chemotherapeutics in rats. Sixty adult male Wistar albino rats were divided into 6 equal groups, 10 animals each. The groups were created as control (weekly i.p. saline injection), Glb (weekly i.p. saline injection and daily oral 100mg/kg Glb), DTX (weekly i.p. injection of 5mg/kg DTX), PTX (weekly i.p. injection of 4mg/kg PTX), DTX+Glb (weekly i.p. injection of 5mg/kg DTX and daily oral 100mg/kg Glb) and PTX+Glb (weekly i.p. injection of 4mg/kg PTX and daily oral 100mg/kg Glb). Following 10-week chronic application, spermatological, biochemical, histopathological, cytopathological and immunohistochemical examinations were performed. DTX and PTX caused significant decreases in absolute and relative weights of all reproductive organs, testosterone level, sperm motility, concentration, Bcl-2 anti-apoptotic immunopositive cell scores of testes and spermatozoa as well as catalase activity in epididymal tissue, superoxide dismutase and glutathione peroxidase activities of testicular and epididymal tissues when compared with the control group. Both drugs also significantly increased abnormal sperm rate, testicular and epididymal malondialdehyde level, Bax pro-apoptotic immunopositive cell scores of testes and spermatozoa, and caused remarkable testicular histological and cytological damages. However, Glb consumption mitigated the PTX-induced decreases in absolute weights of epididimis, seminal vesicles, ventral prostate and both taxanes-induced disturbances in sperm characteristics, imbalances in oxidant/antioxidant system, increments in germ cell apoptosis and testicular histo-and cyto-pathological damages. It was concluded that long-term Glb consumption alleviates the taxanes-induced damages in reproductive system of male rats. Copyright © 2017 Elsevier Masson SAS. All

  15. 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.

  16. 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

  17. Oxidative DNA damage & repair: An introduction.

    PubMed

    Cadet, Jean; Davies, Kelvin J A

    2017-06-01

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

  18. [Curcumin alleviated liver oxidative stress injury of rat induced by paraquat].

    PubMed

    Han, Wenwen; Wu, Dong; Liu, Hong; Lu, Yang; Wang, Lei; Hong, Guangliang; Qiu, Qiaomeng; Lu, Zhongqiu

    2014-05-01

    To investigate the effect of curcumin on liver injury in rats induced by paraquat-mediated oxidative stress and the mechanism underlying its effect. Sixty rats were randomly divided into 4 groups: control group, curcumin control group (curcumin 50 mg/kg), paraquat group (2% paraquat solution 100 mg/kg), and curcumin intervention group (curcumin 50 mg/kg at 15 min, 24 h, or 48 h after paraquat exposure). On days 1, 3, or 7 after paraquat administration, and liver tissue was collected thereafter. The content of malonaldehyde (MDA) and the activities of superoxide dismutase activity (SOD) and catalase (CAT) in the liver tissue were determined by chemical colorimetry. The activities of heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO-1) in the liver tissue were determined by ELISA. The mRNA and protein levels of NF-E2-related factor 2 (Nrf2) were determined by RT-PCR and Western blot, respectively. The pathological changes of liver tissue were examined by optical microscopy. No significant change was observed between the control group and the curcumin control group in any examination of this study (P > 0.05). Both paraquat group and curcumin intervention group showed increase in MDA content, decreases in SOD and CAT activities, increases in HO-1 and NQO-1 activities, and increases in the protein and mRNA levels of Nrf2, in comparison with the control group (P < 0.05 for all except HO-1 activity in paraquat group on day 7). In comparison with the parquet group on the same day, the curcumin intervention group showed decrease in MDA content, increases in the activities of SOD, CAT, HO-1, and NQO-1, and increases in the mRNA and protein levels of Nrf2 on days 1, 3, and 7 (P < 0.05). The pathological examination revealed that the damage of liver tissue in the paraquat group was the most serious on the 3rd day after paraquat exposure, and the damage was consistently alleviated by curcumin intervention on days 1, 3, and 7, as compared with the paraquat group

  19. Immunochemical detection of oxidatively damaged DNA.

    PubMed

    Rossner, Pavel; Sram, Radim J

    2012-04-01

    Oxidatively damaged DNA is implicated in various diseases, including neurodegenerative disorders, cancer, diabetes, cardiovascular and inflammatory diseases as well as aging. Several methods have been developed to detect oxidatively damaged DNA. They include chromatographic techniques, the Comet assay, (32)P-postlabelling and immunochemical methods that use antibodies to detect oxidized lesions. In this review, we discuss the detection of 8-oxo-7,8-dihydro-29-deoxyguanosine (8-oxodG), the most abundant oxidized nucleoside. This lesion is frequently used as a marker of exposure to oxidants, including environmental pollutants, as well as a potential marker of disease progression. We concentrate on studies published between the years 2000 and 2011 that used enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry to detect 8-oxodG in humans, laboratory animals and in cell lines. Oxidative damage observed in these organisms resulted from disease, exposure to environmental pollutants or from in vitro treatment with various chemical and physical factors.

  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. Profiling of rutin-mediated alleviation of cadmium-induced oxidative stress in Zygophyllum fabago.

    PubMed

    Yildiztugay, Evren; Ozfidan-Konakci, Ceyda

    2015-07-01

    Zygophyllum fabago grows in arid, saline soil, or disturbed sites, such as former industrial or mining areas. This species is able to grow in coarse mineral substrates contaminated with heavy metals. To investigate the effects of the flavonoid rutin (Rtn) on certain heavy metal stress responses such as antioxidant defense systems and water status, seedlings were subjected to 100 and 200 μM CdCl2 treatment without or with 0.25 and 1 mM Rtn for 7 and 14 d (days). Cd stress decreased growth (RGR), water content (RWC), leaf osmotic potential (Ψ(Π)), and chlorophyll fluorescence, all of which could be partly alleviated by addition of Rtn. Activities of superoxide dismutase, peroxidase (POX), ascorbate peroxidase, and glutathione reductase increased within the first 7 d after exposure to Cd. However, failure of antioxidant defense in the scavenging of reactive oxygen species (ROS) was evidenced by an abnormal rise in superoxide anion radical ( O2(•-)) and hydrogen peroxide contents and a decline in hydroxyl radical (OH(•)) scavenging activity, resulting in enhancement of lipid peroxidation (TBARS) as a marker of Cd-induced oxidative stress. However, exogenously applied Rtn considerably improved the stress tolerance of plants via a reduction in Cd accumulation, modulation of POX activity, increase of proline (Pro) content, decrease in TBARS and ROS content and consequent lowering of oxidative damage of membrane. Overall, 0.25 and 1 mM Rtn could protect Z. fabago from the harmful effects of 100 μM Cd-induced oxidative stress throughout the experiment. © 2014 Wiley Periodicals, Inc.

  2. Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats.

    PubMed

    Gargouri, M; Magné, C; Ben Amara, I; Ben Saad, H; El Feki, A

    2017-02-28

    Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.

  3. Arabinoxylan activates lipid catabolism and alleviates liver damage in rats induced by high-fat diet.

    PubMed

    Chen, Hong; Fu, Yuanfang; Jiang, Xiujuan; Li, Dongmei; Qin, Wen; Zhang, Qing; Lin, Derong; Liu, Yaowen; Tan, Cui; Huang, Zhiqing; Liu, Yuntao; Chen, Daiwen

    2017-06-06

    Arabinoxylan was thought to have the potential to change lipid metabolism and redox homeostasis in human and animal. However, the effect of arabinoxylan on the liver damage induced by high-fat diet needs further exploiting. Six-weeks-old 30 male Sprague-Dawley Rats were assigned randomly to three groups (n = 10 per group), i.e. a control diet (CON) group, a high-fat diet (HF) group and a high-fat diet supplemented with arabinoxylan (6% AX, HF-AX) group. Results showed that final body weight and liver weight were similar in CON group and HF-AX group, but higher in the HF group. In serum, the HF-AX group showed lower triglyceride concentrations than did the HF group. In liver, higher lipoprotein lipase, hepatic lipase, total lipase, and acyl-CoA oxidase activities and lower triglyceride and cholesterol level were observed in the HF-AX group than in the HF group. For the redox homeostasis, arabinoxylan supplemented in HF increased T-SOD activity and GSH-PX activity and reduced MDA + 4-HNE level in liver and/or compared with those in the HF group. Lipid droplets and liver cell damage were observed in the HF group compared with the CON and HF-AX groups. Arabinoxylan could improve lipid metabolic disorder and alleviate liver damage in rats induced by high-fat diet via activating lipid catabolism and suppressing lipid peroxidation. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. 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.

  5. 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.

  6. 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. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. 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.

  8. Electron beam damage in oxides: a review.

    PubMed

    Jiang, Nan

    2016-01-01

    This review summarizes a variety of beam damage phenomena relating to oxides in (scanning) transmission electron microscopes, and underlines the shortcomings of currently popular mechanisms. These phenomena include mass loss, valence state reduction, phase decomposition, precipitation, gas bubble formation, phase transformation, amorphization and crystallization. Moreover, beam damage is also dependent on specimen thickness, specimen orientation, beam voltage, beam current density and beam size. This article incorporates all of these damage phenomena and experimental dependences into a general description, interpreted by a unified mechanism of damage by induced electric field. The induced electric field is produced by positive charges, which are generated from excitation and ionization. The distribution of the induced electric fields inside a specimen is beam-illumination- and specimen-shape- dependent, and associated with the experimental dependence of beam damage. Broadly speaking, the mechanism operates differently in two types of material. In type I, damage increases the resistivity of the irradiated materials, and is thus divergent, resulting in phase separation. In type II, damage reduces the resistivity of the irradiated materials, and is thus convergent, resulting in phase transformation. Damage by this mechanism is dependent on electron-beam current density. The two experimental thresholds are current density and irradiation time. The mechanism comes into effect when these thresholds are exceeded, below which the conventional mechanisms of knock-on and radiolysis still dominate.

  9. 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.

  10. 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.

  11. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Roles of meditation on alleviation of oxidative stress and improvement of antioxidant system.

    PubMed

    Mahagita, Chitrawina

    2010-11-01

    According to MEDLINE/Pubmed search to December 2009, the modulation effects of meditation on oxidative stress have been increasingly investigated for acute, short and long-term effects. Both invasive and noninvasive measurements have been utilized. Long-term transcendental and Zen meditators have been showed to diminish oxidative stress seen by a reduction of lipid peroxidation and biophoton emission. Glutathione level and activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase) have been facilitated in Yoga and Sudarshan Kriya practitioners. One year of Tai Chi training has been reported to promote superoxide dismutase activity and lessen lipid peroxidation. Performing diaphragmatic breathing after exhaustive exercise has attenuated oxidative stress faster than control. These data suggest possible roles of meditation and meditation-based techniques on the decrease of oxidative stress which may assist to prevent and/or alleviate deterioration of related diseases. However, further research needs to elucidate the cellular and molecular mechanisms which remain challenge to accomplish.

  13. [Recombinant Trichinella spiralis-53000 protein alleviates liver damage due to lipopolysaccharides via M2 macrophage activation].

    PubMed

    Chen, Zhibin; Tang, Hao; Li, Zhenyu; Liang, Yanbing; Wu, Jingguo; Zeng, Lijin; Yang, Qing; Liang, Huaping; Ma, Zhongfu

    2014-08-01

    To evaluate if recombinant Trichinella spiralis-53 000 protein (rTsP53) could alleviate liver damage caused by lipopolysaccharides (LPS) via M2 macrophage activation. Sixty male BALB/c mice were randomly divided into LPS group, LPS + phosphate buffer saline (PBS) group and rTsP53 intervention group by random number table, with 20 mice in each group. Intraperitoneal injection of 15 μg/kg LPS was performed for all the mice in the three groups after 8 hours of fasting. The mice in LPS + PBS group were injected with PBS after 1 hour of LPS injection. The mice in the rTsP53 intervention group were injected with rTsP53 (5 mg/kg) after 1 hour of LPS injection. After 48 hours all the mice were sacrificed. Peritoneal macrophages were harvested and flow cytometry (FCM) was used to detect markers CCR7 (M1) and CD206 (M2) of macrophages. Hepatic tissue was harvested for pathological study after hematoxylin-eosin (HE) staining, and double staining immunofluorescence was used to detect F4/80⁺ HLA-DR⁺ and F4/80⁺ CD163⁺. Peripheral blood serum was harvested to detect the levels of aspartate transaminase (AST) and alanine transaminase (ALT). Compared with LPS and LPS + PBS groups, survival rate of mice of rTsP53 intervention group was significantly elevated (90% vs. 25%, 30%, both P<0.01), and the pathological injury of the liver was significantly ameliorated, and the hepatic structure was better preserved. The transaminase in rTsP53 intervention group was significantly lower than that of LPS and LPS + PBS groups (ALT: 97.7 ± 8.5 U/L vs. 181.7 ± 19.5 U/L, 173.7 ± 17.2 U/L; AST: 142.7 ± 12.1 U/L vs. 235.7 ± 9.9 U/L, 213.7 ± 6.7 U/L, all P<0.05), FITC-CD206⁺ proportion of peritoneal macrophage was significantly higher [(17.75 ± 0.30)% vs. (1.38 ± 0.13)%, (1.36 ± 0.05)%, both P<0.05] while PE-CCR7(+) proportion [(6.89 ± 0.11)% vs. (15.30 ± 0.64)%, (14.96 ± 0.93)%, both P<0.05] was significantly lower. Fluorescence intensity of macrophages with F4/80⁺ CD163

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. MiR-21 alleviates secondary blood-brain barrier damage after traumatic brain injury in rats.

    PubMed

    Ge, Xintong; Han, Zhaoli; Chen, Fanglian; Wang, Haichen; Zhang, Baoliang; Jiang, Rongcai; Lei, Ping; Zhang, Jianning

    2015-04-07

    Our recent studies have identified increased expression of miR-21 in brain following traumatic brain injury (TBI), which alleviated brain edema that related to the blood-brain barrier (BBB) leakage. To analyze the potential effect of miR-21 on secondary BBB damage after TBI, we employed the fluid percussion injury rat model and manipulated the expression level of miR-21 in brain. We found that miR-21 level in brain microvascular endothelial cells (BMVECs) in lesioned cerebral cortex can be upregulated or downregulated by intracerebroventricular infusion of miR-21 agomir or antagomir. Upregulated miR-21 level conferred a better neurological outcome of TBI, and alleviated TBI-induced secondary BBB damage and loss of tight junction proteins. To explore the molecular mechanism underlying this protective effect, we detected the impact of miR-21 on the expression of Angiopoietin-1(Ang-1) and Tie-2, which can promote the expression of tight junction proteins and amplify BBB stabilization. We found that miR-21 exerts the protective effect on BBB by activating the Ang-1/Tie-2 axis in BMVECs. Thus, miR-21 could be a potential therapeutic target for interventions of secondary BBB damage after TBI. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Oxidative and alkylating damage in DNA.

    PubMed

    Martinez, Glaucia R; Loureiro, Ana Paula M; Marques, Sabrina A; Miyamoto, Sayuri; Yamaguchi, Lydia F; Onuki, Janice; Almeida, Eduardo A; Garcia, Camila C M; Barbosa, Lívea F; Medeiros, Marisa H G; Di Mascio, Paolo

    2003-11-01

    Modification of cellular DNA upon exposure to reactive oxygen and nitrogen species is the likely initial event involved in the induction of the mutagenic and lethal effects of various oxidative stress agents. Evidence has been accumulated for the significant implication of singlet oxygen (1O(2)), generated as the result of UVA activation of endogenous photosensitizers as porphyrins and flavins. 7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxodGuo) has been shown to be the exclusive product of the reaction of 1O(2) with the guanine moiety of cellular DNA, in contrast to the hydroxyl radical, which reacts almost indifferently with all the nucleobases and the sugar moiety of DNA. Furthermore 8-oxodGuo is also produced by other oxidants and can be used as an ubiquitous biomarker of DNA oxidation but can not be a specific marker of any particular species. The role of DNA etheno adducts in mutagenic and carcinogenic processes triggered by known occupational and environmental carcinogens has also been studied. Much interest in etheno adducts resulted from the detection of increased levels of 1,N(6)-etheno-2'-deoxyadenosine and 3,N(4)-etheno-2'-deoxycytidine in DNA from human, rat and mouse tissues under pathophysiological conditions associated with oxidative stress. A method involving on-line HPLC with electrospray tandem mass spectrometry detection has been developed for the analysis of 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilondGuo) in DNA. This methodology permits direct quantification of 20 fmol (7.4 adducts/10(8) dGuo) of the etheno adduct from approximately 350 microg of crude DNA hydrolysates. This method provides the first evidence of the occurrence of 1,N(2)-epsilondGuo as a basal endogenous lesion and may be utilized to better assess the biological consequences of etheno DNA damage under normal and pathological conditions. This work addresses the importance of isotope labeling associated with mass spectrometry technique for biomolecule damage studies.

  10. Effectiveness of orally administered cupric oxide needles in alleviating hypocupraemia in sheep and cattle.

    PubMed

    Suttle, N F

    1981-05-09

    The oral administration of a small dose of cupric oxide "needles" (CuOn), providing 0.5 g copper, to hypocupraemic ewes maintained on a copper-deficient diet alleviated hypocupraemia for 111 days when the diet was supplemented with molybdenum and sulphate and for 301 days when the diet was not supplemented. The same amount of copper given as cupric sulphate was approximately half as effective. The administration of a large dose of CuOn, providing 40 g copper, to hypocupraemic steers and heifers alleviated hypocupraemia for not less than 41 days, at which time a substantial reserve of copper (428 mg) remained in the liver. The absorbability of copper in CuOn was estimated to be 8.3 per cent and 3.8 per cent (depending on diet) for sheep. It was calculated that enough absorbable copper could be provided in a single dose to meet the net copper requirements of ewes for several years. This new form of copper therapy demands a totally different approach from that associated with parenteral copper usage.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Mamao Pomace Extract Alleviates Hypertension and Oxidative Stress in Nitric Oxide Deficient Rats.

    PubMed

    Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pannangpetch, Patchareewan; Donpunha, Wanida; Sripui, Jintana; Sae-Eaw, Amporn; Boonla, Orachorn

    2015-07-28

    Reactive oxygen species (ROS)-induced oxidative stress plays a major role in pathogenesis of hypertension. Antidesma thwaitesianum (local name: Mamao) is a tropical plant distributed in the tropical/subtropical areas of the world, including Thailand. Mamao pomace (MP), a by-product generated from Mamao fruits, contains large amounts of antioxidant polyphenolic compounds. The aim of this study was to investigate the antihypertensive and antioxidative effects of MP using hypertensive rats. For this purpose, male Sprague-Dawley rats were given Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), in drinking water (50 mg/kg) for three weeks. MP extract was orally administered daily at doses of 100 and 300 mg/kg. L-NAME administration induced marked increase in blood pressure, peripheral vascular resistance, and oxidative stress. MP treatment significantly prevented the increase in blood pressure, hindlimb blood flow and hindlimb vascular resistance of L-NAME treated hypertensive rats (p < 0.05). The antihypertensive effect of MP treatment was associated with suppression of superoxide production from carotid strips and also with an increase in eNOS protein expression and nitric oxide bioavailability. The present results provide evidence for the antihypertensive effect of MP and suggest that MP might be useful as a dietary supplement against hypertension.

  20. Mamao Pomace Extract Alleviates Hypertension and Oxidative Stress in Nitric Oxide Deficient Rats

    PubMed Central

    Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pannangpetch, Patchareewan; Donpunha, Wanida; Sripui, Jintana; Sae-Eaw, Amporn; Boonla, Orachorn

    2015-01-01

    Reactive oxygen species (ROS)-induced oxidative stress plays a major role in pathogenesis of hypertension. Antidesma thwaitesianum (local name: Mamao) is a tropical plant distributed in the tropical/subtropical areas of the world, including Thailand. Mamao pomace (MP), a by-product generated from Mamao fruits, contains large amounts of antioxidant polyphenolic compounds. The aim of this study was to investigate the antihypertensive and antioxidative effects of MP using hypertensive rats. For this purpose, male Sprague-Dawley rats were given Nω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), in drinking water (50 mg/kg) for three weeks. MP extract was orally administered daily at doses of 100 and 300 mg/kg. l-NAME administration induced marked increase in blood pressure, peripheral vascular resistance, and oxidative stress. MP treatment significantly prevented the increase in blood pressure, hindlimb blood flow and hindlimb vascular resistance of l-NAME treated hypertensive rats (p < 0.05). The antihypertensive effect of MP treatment was associated with suppression of superoxide production from carotid strips and also with an increase in eNOS protein expression and nitric oxide bioavailability. The present results provide evidence for the antihypertensive effect of MP and suggest that MP might be useful as a dietary supplement against hypertension. PMID:26225998

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Apple juice concentrate prevents oxidative damage and impaired maze performance in aged mice.

    PubMed

    Tchantchou, Flaubert; Chan, Amy; Kifle, Lydia; Ortiz, Daniela; Shea, Thomas B

    2005-12-01

    Oxidative stress contributes to age-related cognitive decline. In some instances, consumption of fruits and vegetables rich in antioxidant can provide superior protection than supplementation with purified antioxidants. Our prior studies have shown that supplementation with apple juice concentrate (AJC) alleviates oxidative damage and cognitive decline in a transgenic murine model compromised in endogenous antioxidant potential when challenged with a vitamin-deficient, oxidative stress-promoting diet. Herein, we demonstrate that AJC, administered in drinking water, is neuroprotective in normal, aged mice. Normal mice aged either 9-10 months or 2-2.5 years were maintained for 1 month on a complete diet or a diet lacking folate and vitamin E and containing iron as a pro-oxidant, after which oxidative damage was assayed by thiobarbituric acid-reactive substances and cognitive decline as assayed by performance in a standard Y-maze. Mice 9-12 months of age were unaffected by the deficient diet, while older mice demonstrated statistically-increased oxidative damage and poorer performance in a Y maze test. Supplementation with AJC prevented these neurodegenerative effects. These data are consistent with normal aged individuals being susceptible to neurodegeneration following dietary compromise such as folate deficiency, and a hastened onset of neurodegeneration in those individuals harboring a genetic risk factor such as ApoE deficiency. These findings also support the efficacy of antioxidant supplementation, including consumption of antioxidant-rich foods such as apples, in preventing the decline in cognitive performance that accompanies normal aging.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. Taurine Alleviate Hexabromocyclododecane-Induced Cytotoxicity in PC12 Cells via Inhibiting Oxidative Stress.

    PubMed

    Liu, Lu; Guo, Lianying; Xie, Xizhe; Fan, Ning; Li, Yan; Li, Yachen; Zhang, Xiuli

    2017-01-01

    Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant. Its adverse effects on brain had been observed. Taurine, a sulfur amino acid, take part in many brain physiological functions and exhibits protective effects on a variety of detrimental situations. In this paper, we explored the protections of taurine on cytotoxicity induced by HBCD in PC12 cells. PC12 cells were pretreated with taurine (1 mM, 3 mM and 9 mM) for 30 min before 10 μM HBCD treatment for 24 h. Then, the cell survival was assayed by the lactate dehydrogenase (LDH) release and trypan blue dyeing method. The formation of reactive oxygen species (ROS) and a collapse of mitochondrial membrane potential (MMP) were evaluated with a fluorescence microplate reader using the non-fluorescent probe 2'7'-dichlorofluorescin diacetate (DCFH-DA) and the fluorescent cationic dyestuff Rhodamine 123 (Rh 123), respectively. Further, the activity of many antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and the content of glutathione (GSH) were tested by kits. Our results displayed that taurine significantly decreased the cell death induced by HBCD, prevented ROS production and disruption of mitochondrial membrane potential, and reversed the decline of SOD, CAT, GPx activity and GSH content induced by HBCD. These results suggested that taurine could alleviate cytotoxicity induced by HBCD in PC12 cells through inhibition of oxidative stress.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Oxidative DNA damage during night shift work.

    PubMed

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

    2017-09-01

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

  20. 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

  1. 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

  2. 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

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

    PubMed

    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 [Formula: see text] 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.

  4. 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

  5. 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.

  6. Oxidative stress-related liver dysfunction by sodium arsenite: Alleviation by Pistacia lentiscus oil.

    PubMed

    Klibet, Fahima; Boumendjel, Amel; Khiari, Mohamed; El Feki, Abdelfattah; Abdennour, Cherif; Messarah, Mahfoud

    2016-01-01

    Pistacia lentiscus L. (Anacardiaceae) is an evergreen shrub widely distributed throughout the Mediterranean region. Pistacia lentiscus oil (PLo) was particularly known in North African traditional medicine. Thus, people of these regions have used it externally to treat sore throats, burns and wounds, as well as they employed it internally for respiratory allergies. PLo is rich in essential fatty acids, vitamin E and polyphenols. As a very active site of metabolism, liver is reported to be susceptible to arsenic (As) intoxication. The present study evaluates the protective effect of PLo against sodium arsenite-induced hepatic dysfunction and oxidative stress in experimental Wistar rats. Twenty-eight rats were equally divided into four groups; the first served as a control, the remaining groups were respectively treated with PLo (3.3 mL/kg body weight), sodium arsenite (5.55 mg/kg body weight) and a combination of sodium arsenite and PLo. After 21 consecutive days, cellular functions were evaluated by hematological, biochemical and oxidative stress markers. A significant decrease in the levels of red blood cells, haemoglobin (p ≤ 0.001), hematocrit (p ≤ 0.001), reduced glutathione and metallothionein (p ≤ 0.05) associated with a significant increase of malondialdehyde (p ≤ 0.001) were noticed in the arsenic-exposed group when compared to the control. The As-treated group also exhibited an increase in hepatic antioxidant enzymes namely superoxide dismutase, glutathione peroxidase (p ≤ 0.01) and catalase (p ≤ 0.05). However, the co-administration of PLo has relatively reduced arsenic effect. The results showed that arsenic intoxication disturbed the liver pro-oxidant/antioxidant status. PLo co-administration mitigates arsenic-induced oxidative damage in rat.

  7. Engineered drought-induced biosynthesis of α-tocopherol alleviates stress-induced leaf damage in tobacco.

    PubMed

    Espinoza, Analía; San Martín, Alex; López-Climent, María; Ruiz-Lara, Simón; Gómez-Cadenas, Aurelio; Casaretto, José A

    2013-09-15

    Tocopherols are members of the vitamin E complex and essential antioxidant compounds synthesized in chloroplasts that protect photosynthetic membranes against oxidative damage triggered by most environmental stresses. Tocopherol deficiency has been shown to affect germination, retard growth and change responses to abiotic stress, suggesting that tocopherols may be involved in a number of diverse physiological processes in plants. Instead of seeking constitutive synthesis of tocopherols to improve stress tolerance, we followed an inducible approach of enhancing α-tocopherol accumulation under dehydration conditions in tobacco. Two uncharacterized stress inducible promoters isolated from Arabidopsis and the VTE2.1 gene from Solanum chilense were used in this work. VTE2.1 encodes the enzyme homogentisate phytyltransferase (HPT), which catalyzes the prenylation step in tocopherol biosynthesis. Transgenic tobacco plants expressing ScVTE2.1 under the control of stress-inducible promoters showed increased levels of α-tocopherol when exposed to drought conditions. The accumulation of α-tocopherol correlated with higher water content and increased photosynthetic performance and less oxidative stress damage as evidenced by reduced lipid peroxidation and delayed leaf senescence. Our results indicate that stress-induced expression of VTE2.1 can be used to increase the vitamin E content and to diminish detrimental effects of environmental stress in plants. The stress-inducible promoters introduced in this work may prove valuable to future biotechnological approaches in improving abiotic stress resistance in plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

  8. Nitric oxide alleviates silver nanoparticles (AgNps)-induced phytotoxicity in Pisum sativum seedlings.

    PubMed

    Tripathi, Durgesh Kumar; Singh, Swati; Singh, Shweta; Srivastava, Prabhat Kumar; Singh, Vijay Pratap; Singh, Samiksha; Prasad, Sheo Mohan; Singh, Prashant Kumar; Dubey, Nawal Kishore; Pandey, Avinash Chand; Chauhan, Devendra Kumar

    2017-01-01

    Understanding the adverse impact of nanoparticles in crop plants has emerged as one of the most interesting fields of plant research. Therefore, this study has been conducted to investigate the impact of silver nanoparticles (AgNps) on Pisium sativum seedlings. Besides this, we have also tested whether nitric oxide (NO) is capable of reducing toxicity of AgNps or not. NO has been found as one of the most fascinating molecules, capable of enhancing plant tolerance to different environmental stresses. The results of the present study showed that AgNps treatments (1000 μM and 3000 μM) significantly declined growth parameters, photosynthetic pigments and chlorophyll fluorescence of pea seedlings, which could be correlated with increased accumulation of Ag in root and shoot of pea seedlings. In contrast, addition of SNP (100 μM; a donor of NO) successfully ameliorated AgNp-induced adverse effects on these parameters as it reduced accumulation of Ag and repaired damaged tissues. Levels of oxidative stress markers (SOR, H2O2 and MDA) were enhanced while their levels significantly reduced under SNP addition. AgNps (1000 μM and 3000 μM) significantly stimulated the activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX) while inhibited activities of glutathione reductase (GR) and dehydroascorbate reductase (DHAR). AgNps also considerably declined the total ascorbate and glutathione contents and severely damaged leaf and root anatomical structures. On the other hand, addition of SNP further increased the level of SOD, APX, GR and DHAR and significantly increased the decreased levels of total ascorbate and glutathione contents, and repaired anatomical structures. In conclusion, this study suggests that AgNps treatments adversely decreased growth, pigments and photosynthesis due to enhanced level of Ag and oxidative stress. However, SNP addition successfully ameliorates adverse impact of AgNps on pea seedlings by regulating the Ag uptake, antioxidant

  9. Synthesis of damaged DNA containing the oxidative lesion 3'-oxothymidine.

    PubMed

    Bedi, Mel F; Li, Weiye; Gutwald, Taylor; Bryant-Friedrich, Amanda C

    2017-09-01

    Oxidative events that take place during regular oxygen metabolism can lead to the formation of organic or inorganic radicals. The interaction of these radicals with macromolecules in the organism and with DNA in particular is suspected to lead to apoptosis, DNA lesions and cell damage. Independent generation of DNA lesions resulting from oxidative damage is used to promote the study of their effects on biological systems. An efficient synthesis of oligodeoxyribonucleotides (ODNs) containing the oxidative damage lesion 3'-oxothymidine has been accomplished via incorporation of C3'-hydroxymethyl thymidine as its corresponding 5'-phosphoramidite. Through oxidative cleavage using sodium periodate in aqueous solution, the lesion of interest is easily generated. Due to its inherent instability it cannot be directly isolated, but must be generated in situ. 3'-Oxothymidine is a demonstrated damage product formed upon generation of the C3'-thymidinyl radical in ODN. Copyright © 2017. Published by Elsevier Ltd.

  10. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  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. Repair of Oxidative DNA Damage in Saccharomyces cerevisiae.

    PubMed

    Chalissery, Jisha; Jalal, Deena; Al-Natour, Zeina; Hassan, Ahmed H

    2017-03-01

    Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomolecules including DNA and consequently activates various DNA repair pathways. The nature of DNA damage and the cell cycle stage at which DNA damage occurs determine the appropriate repair pathway to rectify the damage. Oxidized DNA bases are primarily repaired by base excision repair and nucleotide incision repair. Nucleotide excision repair acts on lesions that distort DNA helix, mismatch repair on mispaired bases, and homologous recombination and non-homologous end joining on double stranded breaks. Post-replication repair that overcomes replication blocks caused by DNA damage also plays a crucial role in protecting the cell from the deleterious effects of oxidative DNA damage. Mitochondrial DNA is also prone to oxidative damage and is efficiently repaired by the cellular DNA repair machinery. In this review, we discuss the DNA repair pathways in relation to the nature of oxidative DNA damage in Saccharomyces cerevisiae. Copyright © 2017 Elsevier B.V. All rights reserved.

  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. 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.

  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. 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.

  17. Chronic treatment with resveratrol, a natural polyphenol found in grapes, alleviates oxidative stress and apoptotic cell death in ovariectomized female rats subjected to chronic cerebral hypoperfusion.

    PubMed

    Ozacmak, Veysel Haktan; Sayan-Ozacmak, Hale; Barut, Figen

    2016-05-01

    Resveratrol appears to have neuroprotective potential in various animal models of brain disorders including cerebral ischemia and neurodegenerative diseases. Chronic cerebral hypoperfusion is a well-known pathological condition contributing to the neurodegenerative diseases such as vascular dementia. Purpose of the present study is to evaluate the possible therapeutic potential of resveratrol in a model of vascular dementia of ovariectomized female rats. Assessment of the potential was based on the determination of brain oxidative status, caspase-3 level, glial fibrillary acidic protein (GFAP), and neuronal damage on hippocampus and cerebral cortex. For creating the model of chronic cerebral hypoperfusion, ovariectomized female Wistar rats were subjected to the modified two vessel occlusion method, with the right common carotid artery being occluded first and the left one a week later. At the 15th day following the ligation, neuronal damage was accompanied by the increased immunoreactivities of both GFAP and caspase-3, and significant neurodegeneration was evident in the hippocampus and cortex, all of which were significantly alleviated with resveratrol treatment (10 mg/kg). Biochemical analysis revealed that the resveratrol treatment decreased lipid peroxidation and restored reduced glutathione level as well. The collected data of the present study suggest that the administration of resveratrol may provide a remarkable therapeutic benefit for vascular dementia, which is most likely related to the prevention of both apoptotic cell death and oxidative stress. We believe that therapeutic efficacy of resveratrol deserves to be tested for potential clinical application in postmenopausal elderly women suffering from vascular dementia.

  18. 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

  19. Pathology of perinatal brain damage: background and oxidative stress markers.

    PubMed

    Tonni, Gabriele; Leoncini, Silvia; Signorini, Cinzia; Ciccoli, Lucia; De Felice, Claudio

    2014-07-01

    To review historical scientific background and new perspective on the pathology of perinatal brain damage. The relationship between birth asphyxia and subsequent cerebral palsy has been extensively investigated. The role of new and promising clinical markers of oxidative stress (OS) is presented. Electronic search of PubMed-Medline/EMBASE database has been performed. Laboratory and clinical data involving case series from the research group are reported. The neuropathology of birth asphyxia and subsequent perinatal brain damage as well as the role of electronic fetal monitoring are reported following a review of the medical literature. This review focuses on OS mechanisms underlying the neonatal brain damage and provides different perspective on the most reliable OS markers during the perinatal period. In particular, prior research work on neurodevelopmental diseases, such as Rett syndrome, suggests the measurement of oxidized fatty acid molecules (i.e., F4-Neuroprostanes and F2-Dihomo-Isoprostanes) closely related to brain white and gray matter oxidative damage.

  20. 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...

  1. 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...

  2. 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.

  3. Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways.

    PubMed

    Li, Xiang; Michaeloudes, Charalambos; Zhang, Yuelin; Wiegman, Coen H; Adcock, Ian M; Lian, Qizhou; Mak, Judith C W; Bhavsar, Pankaj K; Chung, Kian Fan

    2017-09-11

    Oxidative stress-induced mitochondrial dysfunction may contribute to inflammation and remodeling in chronic obstructive pulmonary disease (COPD). Mesenchymal stem cells (MSCs) protect against lung damage in animal models of COPD. It is unknown whether these effects occur through attenuating mitochondrial dysfunction in airway cells. To examine the effect of induced-pluripotent stem cell-derived MSCs (iPSC-MSCs) on oxidative stress-induce mitochondrial dysfunction in human airway smooth muscle cells (ASMCs) in vitro and in mouse lungs in vivo. ASMCs were co-cultured with iPSC-MSCs in the presence of cigarette smoke medium (CSM), and mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm) and apoptosis were measured. Conditioned media from iPSC-MSCs and trans-well co-cultures were used to detect any paracrine effects. The effect of systemic injection of iPSC-MSCs on airway inflammation and hyper-responsiveness in ozone-exposed mice was also investigated. Co-culture of iPSC-MSCs with ASMCs attenuated CSM-induced mitochondrial ROS, apoptosis and ΔΨm loss in ASMCs. iPSC-MSC-conditioned media or trans-well co-cultures with iPSC-MSCs reduced CSM-induced mitochondrial ROS but not ΔΨm or apoptosis in ASMCs. Mitochondrial transfer from iPSC-MSCs to ASMCs was observed after direct co-culture and was enhanced by CSM. iPSC-MSCs attenuated ozone-induced mitochondrial dysfunction, airway hyper-responsiveness and inflammation in mouse lungs. iPSC-MSCs offered protection against oxidative stress-induced mitochondrial dysfunction in human ASMCs and in mouse lungs, whilst reducing airway inflammation and hyper-responsiveness. These effects are, at least partly, dependent on cell-cell contact that allows for mitochondrial transfer, and paracrine regulation. Therefore, iPSC-MSCs show promise as a therapy for oxidative stress-dependent lung diseases such as COPD. Copyright © 2017. Published by Elsevier Inc.

  4. 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.

  5. Oxidative Damage in the Guinea Pig Hippocampal Slice

    DTIC Science & Technology

    1989-01-01

    oxidation to the observed damage. the actions of the oxidants, chloramine -T and N-chlorosuccinimide (NCS). were studied on electrophysiological...hippocampus evoked a population postsynaptic potential (population PSP) in the dendritic layer and a population spike in the cell body layer. Chloramine -T (25...produced by free radicals but can rot account for the postsynaptic effects. Keywords- Chloramine -T. N-chlorosuccinimide. Oxidation. Free radical

  6. Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice.

    PubMed

    Sahu, Bidya Dhar; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Borkar, Roshan M; Srinivas, R; Sistla, Ramakrishna

    2016-01-01

    Doxorubicin is a widely used anthracycline derivative anticancer drug. Unfortunately, the clinical use of doxorubicin has the serious drawback of cardiotoxicity. In this study, we investigated whether baicalein, a bioflavonoid, can prevent doxorubicin-induced cardiotoxicity in vivo and we delineated the possible underlying mechanisms. Male BALB/c mice were treated with either intraperitoneal doxorubicin (15 mg/kg divided into three equal doses for 15 days) and/or oral baicalein (25 and 50 mg/kg for 15 days). Serum markers of cardiac injury, histology of heart, parameters related to myocardial oxidative stress, apoptosis and inflammation were investigated. Treatment with baicalein reduced doxorubicin-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and ameliorated the histopathological damage. Baicalein restored the doxorubicin-induced decrease in both enzymatic and non-enzymatic myocardial antioxidants and increased the myocardial expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Further studies showed that baicalein could inverse the Bax/Bcl-2 ratio, suppress doxorubicin-induced p53, cleaved caspase-3 and PARP expression and prevented doxorubicin-induced DNA damage. Baicalein treatment also interferes with doxorubicin-induced myocardial NF-κB signaling through inhibition of IκBα phosphorylation and nuclear translocation of p65 subunit. Doxorubicin elevated iNOS and nitrites levels were also significantly decreased in baicalein treated mice. However, we did not find any significant change (p>0.05) in the myocardial TNF-α and IL-6 levels in control and treated animals. Our finding suggests that baicalein might be a promising molecule for the prevention of doxorubicin-induced cardiotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 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.

  8. 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

  9. 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

  10. 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

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

    PubMed

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

    2017-03-07

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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. DNA damage and oxidative status in PFAPA syndrome.

    PubMed

    Tuğrul, Selahattin; Doğan, Remzi; Kocyigit, Abdurrahim; Torun, Emel; Senturk, Erol; Ozturan, Orhan

    2015-10-01

    PFAPA syndrome is a clinical entity of unknown etiology which presents with periodic episodes of fever, aphthous stomatitis, tonsillitis or pharyngitis, and cervical adenitis. In this study we investigated DNA damage and the oxidative stress parameters in patients diagnosed with PFAPA, to elucidate the underlying pathophysiological mechanism of this syndrome. Thirty-one patients diagnosed with PFAPA (Group 1), 22 patients diagnosed with normal tonsillitis or pharyngitis (Group 2), and 20 healthy volunteers (Group 3) were included in our study. Heparinized peripheral blood samples were drawn from all patients and volunteers. DNA damage was assessed by single cell alkaline electrophoresis assay in peripheral mononuclear leukocytes. Plasma levels of total antioxidant status (TAS) and total oxidative status (TOS) were determined by using a novel automated measurement method, and oxidative stress index (OSI) was calculated. DNA damage in the mononuclear leukocytes of Group 1 was significantly higher than that of Group 2 and Group 3. The oxidative stress parameters revealed that the TOS and OSI values of Group 1 were significantly higher than those of Group 2 and Group 3. TAS values of Group 1 were significantly lower than those of Group 2 and Group 3. Correlation analysis of Group 1 demonstrated a significant correlation between TOS, one of the oxidative stress parameters, and DNA damage. Correlations between DNA damage and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were also significant. Our study indicated that both the inflammatory and the oxidative stress parameters were significantly increased in patients with PFAPA syndrome, accompanied by a significant positive correlation between DNA damage and oxidative stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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

  1. 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

  2. Characterization of Oxidative Guanine Damage and Repair in Mammalian Telomeres

    PubMed Central

    Wang, Zhilong; Rhee, David B.; Lu, Jian; Bohr, Christina T.; Zhou, Fang; Vallabhaneni, Haritha; de Souza-Pinto, Nadja C.; Liu, Yie

    2010-01-01

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

  3. 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.

  4. Effect of procyandin oligomers on oxidative hair damage.

    PubMed

    Kim, Moon-Moo

    2011-02-01

    Procyanidins are a subclass of flavonoids and consist of oligomers of catechin that naturally occur in plants and are known to exert many physiological effects, including antioxidant, anti-inflammatory, and enzyme inhibitory effects. These possible inhibitory effects of the procyanidins were known to involve metal chelation, radical trapping, or direct enzyme binding. The purpose of this study was to investigate the effect of procyandin oligomers on hair damage induced by oxidative stress. In this study, several methods for evaluating oxidative damage in bleached hair are utilized to analyze the protective effect of procyandin oligomers against oxidative hair damage. It was observed that procyanidin oligomers strongly bind to keratin in hair and inhibit the breakdown of hair caused by oxidative damage in an analysis of hair using electrophoresis, transmission electron microscope, and fluorescence dye. These results confirm that procyanidin oligomers can be applicable as a potential candidate to the development of hair care with protective effect on hair damage. © 2011 John Wiley & Sons A/S.

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

    PubMed

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

    2013-06-01

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

  6. 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

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

    PubMed

    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.

  8. 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.

  9. Microsomal oxidative damage promoted by acetaminophen metabolism.

    PubMed

    Letelier, María Eugenia; López-Valladares, Miguel; Peredo-Silva, Liliana; Rojas-Sepúlveda, Daniel; Aracena, Paula

    2011-10-01

    Adverse reactions of acetaminophen have been associated to oxidative stress, which may be elicited by reactive oxygen species (ROS) and/or production of the metabolite NAPQI. Both phenomena would arise through the activity of liver cytochrome P450 (CYP450) system, but their contribution to this oxidative stress is yet to be clarified. A NADPH oxidase activity has been proposed in rat liver microsomes. This activity may be due to the presence of NAD(P)H oxidase (NOX) isoforms in liver endoplasmic reticulum. Both NOX and the CYP450 system activities can catalyze ROS generation using NADPH as a cofactor. Therefore, acetaminophen biotransformation, which requires NADPH, may promote ROS generation through either activity or both. To discriminate between these possibilities, rat liver microsomes were incubated with acetaminophen and NADPH in the presence or absence of specific inhibitors. Incubation with NADPH and acetaminophen elicited lipid peroxidation and decreased thiol content and glutathione-S-transferase (GST) activity. The NOX inhibitors apocynin and plumbagin prevented all these phenomena but the decrease in thiol content. In contrast, this decrease was completely prevented by the specific CYP450 system inhibitor SKF-525A. These data suggest that ROS generation following incubation of microsomes with acetaminophen and NADPH appears to be mainly caused by a NOX activity. In light of these data, toxicity of acetaminophen is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Nek7 Protects Telomeres from Oxidative DNA Damage by Phosphorylation and Stabilization of TRF1.

    PubMed

    Tan, Rong; Nakajima, Satoshi; Wang, Qun; Sun, Hongxiang; Xue, Jing; Wu, Jian; Hellwig, Sabine; Zeng, Xuemei; Yates, Nathan A; Smithgall, Thomas E; Lei, Ming; Jiang, Yu; Levine, Arthur S; Su, Bing; Lan, Li

    2017-03-02

    Telomeric repeat binding factor 1 (TRF1) is essential to the maintenance of telomere chromatin structure and integrity. However, how telomere integrity is maintained, especially in response to damage, remains poorly understood. Here, we identify Nek7, a member of the Never in Mitosis Gene A (NIMA) kinase family, as a regulator of telomere integrity. Nek7 is recruited to telomeres and stabilizes TRF1 at telomeres after damage in an ATM activation-dependent manner. Nek7 deficiency leads to telomere aberrations, long-lasting γH2AX and 53BP1 foci, and augmented cell death upon oxidative telomeric DNA damage. Mechanistically, Nek7 interacts with and phosphorylates TRF1 on Ser114, which prevents TRF1 from binding to Fbx4, an Skp1-Cul1-F box E3 ligase subunit, thereby alleviating proteasomal degradation of TRF1, leading to a stable association of TRF1 with Tin2 to form a shelterin complex. Our data reveal a mechanism of efficient protection of telomeres from damage through Nek7-dependent stabilization of TRF1. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Neuroprotective effects of resveratrol on ischemic injury mediated by improving brain energy metabolism and alleviating oxidative stress in rats.

    PubMed

    Li, Hua; Yan, Zhiying; Zhu, Jian; Yang, Jing; He, Jianshe

    2011-01-01

    In this study, we investigated whether resveratrol could protect against ischemic injury by improving brain energy metabolism and alleviating oxidative stress. Male rats were divided into three groups: sham operation, ischemia treatment, and ischemia combined with resveratrol treatment (resveratrol-treated group, 30 mg/kg intraperitoneally for 7 days). Cerebral ischemia was induced by using the model of middle cerebral artery occlusion. The dialysates in hypothalamus were obtained by brain microdialysis technique. The effects of resveratrol on neurologic functions and histopathologic changes were evaluated. The levels of ATP, ADP, AMP, adenosine, inosine, hypoxanthine and xanthine in microdialysate were monitored by HPLC analysis. The levels of malondialdehyde and the activities of xanthine oxidase in brain tissues were analyzed in three groups. This study shows that the ischemic infarcts were significantly reduced and neurological functions were improved in resveratrol-treated group compared to ischemia group. The analysis results show that resveratrol treatments remarkably enhanced the level of glucose, ATP and energy charge; decreased the levels of lactate during I/R period. Resveratrol treatments significantly increased the basal levels of adesonine and inosine, inhibited the elevations of hypoxanthine and xanthine levels and remarkably decreased xanthine oxidase activity and malondialdehyde levels. This study provides in vivo evidence that resveratrol could exert neuroprotective effect against ischemia injury by improving brain energy metabolism and alleviating oxidative stress via inhibiting xanthine oxidase activity and preventing the production of hypoxanthine, xanthine and oxygen radicals during ischemia/reperfusion. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Alleviation effect of arbutin on oxidative stress generated through tyrosinase reaction with L-tyrosine and L-DOPA.

    PubMed

    Tada, Mika; Kohno, Masahiro; Niwano, Yoshimi

    2014-10-09

    Hydroxyl radical that has the highest reactivity among reactive oxygen species (ROS) is generated through L-tyrosine-tyrosinase reaction. Thus, the melanogenesis might induce oxidative stress in the skin. Arbutin (p-hydroxyphenyl-β-D-glucopyranoside), a well-known tyrosinase inhibitor has been widely used for the purpose of skin whitening. The aim of the present study was to examine if arbutin could suppress the hydroxyl radical generation via tyrosinase reaction with its substrates, L-tyrosine and L-DOPA. The hydroxyl radical, which was determined by an electron spin resonance-spin trapping technique, was generated by the addition of not only L-tyrosine but L-DOPA to tyrosinase in a concentration dependent manner. Arbutin could inhibit the hydroxyl radical generation in the both reactions. It is presumed that arbutin could alleviate oxidative stress derived from the melanogenic pathway in the skin in addition to its function as a whitening agent in cosmetics.

  13. 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.

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

    PubMed

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

    2016-08-01

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

  15. 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.

  16. In vivo oxidation and surface damage in retrieved ethylene oxide-sterilized total knee arthroplasties.

    PubMed

    MacDonald, Daniel; Hanzlik, Josa; Sharkey, Peter; Parvizi, Javad; Kurtz, Steven M

    2012-07-01

    Gas sterilization (eg, ethylene oxide [EtO] and gas plasma) was introduced for polyethylene to reduce oxidation due to free radicals occurring during radiation sterilization. Recently, oxidation has been observed in polyethylenes with undetectable levels of free radicals, which were expected to be oxidatively stable. It is unclear whether in vivo oxidation will occur in unirradiated inserts sterilized with EtO. We analyzed the oxidation, mechanical behavior, and surface damage mechanisms of tibial inserts of a single design sterilized using EtO. We collected 20 EtO-sterilized tibial inserts at revision surgeries. We assessed oxidative using Fourier transform infrared spectroscopy and mechanical properties using the small punch test. Surface damage was assessed using damage scoring techniques and micro-CT. Oxidation indexes were low and uniform between the regions. The subtle changes did not affect the mechanical properties of the polymer. The dominant surface damage modes included burnishing, abrasion, and third-body wear. There was no evidence of delamination in the retrievals. The retrieved EtO-sterilized UHMWPE retrievals remained stable with respect to both oxidative and mechanical properties for up to 10 years in vivo. We did observe slight measurable amounts of oxidation in the inserts; however, it was far below levels that would be expected to compromise the strength of the polymer. Due to the stable oxidative and mechanical properties, EtO-sterilized tibial components appear to be an effective alternative to gamma-sterilized inserts, at least in short-term implantations.

  17. Contribution of Oxidative Damage to Antimicrobial Lethality▿

    PubMed Central

    Wang, Xiuhong; Zhao, Xilin

    2009-01-01

    A potential pathway linking hydroxyl radicals to antimicrobial lethality was examined by using mutational and chemical perturbations of Escherichia coli. Deficiencies of sodA or sodB had no effect on norfloxacin lethality; however, the absence of both genes together reduced lethal activity, consistent with rapid conversion of excessive superoxide to hydrogen peroxide contributing to quinolone lethality. Norfloxacin was more lethal with a mutant deficient in katG than with its isogenic parent, suggesting that detoxification of peroxide to water normally reduces quinolone lethality. An iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) reduced the lethal activity of norfloxacin, indicating that norfloxacin-stimulated accumulation of peroxide affects lethal activity via hydroxyl radicals generated through the Fenton reaction. Ampicillin and kanamycin, antibacterials unrelated to fluoroquinolones, displayed behavior similar to that of norfloxacin except that these two agents showed hyperlethality with an ahpC (alkyl hydroperoxide reductase) mutant rather than with a katG mutant. Collectively, these data are consistent with antimicrobial stress increasing the production of superoxide, which then undergoes dismutation to peroxide, from which a highly toxic hydroxyl radical is generated. Hydroxyl radicals then enhance antimicrobial lethality, as suggested by earlier work. Such findings indicate that oxidative stress networks may provide targets for antimicrobial potentiation. PMID:19223646

  18. Obesity Exacerbates Sepsis-Induced Oxidative Damage in Organs.

    PubMed

    Petronilho, Fabricia; Giustina, Amanda Della; Nascimento, Diego Zapelini; Zarbato, Graciela Freitas; Vieira, Andriele Aparecida; Florentino, Drielly; Danielski, Lucinéia Gainski; Goldim, Mariana Pereira; Rezin, Gislaine Tezza; Barichello, Tatiana

    2016-12-01

    Sepsis progression is linked to the imbalance between reactive oxygen species and antioxidant enzymes. Sepsis affects multiple organs, but when associated with a chronic inflammatory disease, such as obesity, it may be exacerbated. We hypothesized that obesity could aggravate the oxidative damage to peripheral organs of rats submitted to an animal model of sepsis. Male Wistar rats aged 8 weeks received hypercaloric nutrition for 2 months to induce obesity. Sepsis was induced by cecal ligation and puncture (CLP) procedure, and sham-operated rats were considered as control group. The experimental groups were divided into sham + eutrophic, sham + obese, CLP + eutrophic, and CLP + obese. Twelve and 24 h after surgery, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the liver, lung, kidney, and heart. The data indicate that obese rats subjected to sepsis present oxidative stress mainly in the lung and liver. This alteration reflected an oxidative damage to lipids and proteins and an imbalance of SOD and CAT levels, especially 24 h after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate sepsis-induced damage in peripheral organs.

  19. Can graphene oxide cause damage to eyesight?

    PubMed

    Yan, Lu; Wang, Yaping; Xu, Xu; Zeng, Chao; Hou, Jiangping; Lin, Mimi; Xu, Jingzhou; Sun, Fei; Huang, Xiaojie; Dai, Liming; Lu, Fan; Liu, Yong

    2012-06-18

    As graphene becomes one of the most exciting candidates for multifunctional biomedical applications, contact between eyes and graphene-based materials is inevitable. On the other hand, eyes, as a special organ in the human body, have unique advantages to be used for testing new biomedical research and development, such as drug delivery. Intraocular biocompatible studies on graphene-related materials are thus essential. Here, we report our recent studies on intraocular biocompatibility and cytotoxicity of graphene oxide (GO) both in vitro and in vivo. The successful preparation of GO nanosheets was confirmed using atomic force microscopy, contact angle analyzer, Fourier transform infrared spectroscopy, and Raman spectroscopy. The influence of GO on human retinal pigment epithelium (RPE) cells in terms of the cell morphology, viability, membrane integrity, and apoptosis was investigated using various techniques, including optical micrography, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, and apoptosis assay. The addition of GO had little influence on cell morphology, but the change was visible after long-time culturing. RPE cells showed higher than 60% cell viability by CCK-8 assay in GO solutions and less than 8% LDH release, although a small amount of apoptosis (1.5%) was observed. In vitro results suggested good biocompatibility of GO to RPE cells with slight adverse influence, on the cell viability and morphology in long-time periods, along with aggregation of GO. Thus, some further studies are needed to clarify the cytotoxicity mechanism of GO. GO intravitreally injected eyes showed few changes in eyeball appearance, intraocular pressure (IOP), eyesight, and histological photos. Our results suggested that GO did not cause any significant toxicity to the cell growth and proliferation. Intravitreal injection of GO into rabbits' eyes did not lead to much change in the eyeball appearance, IOP, electroretinogram, and histological examination.

  20. Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage.

    PubMed

    Farfán Labonne, Blanca Eugenia; Gutiérrez, Mario; Gómez-Quiroz, Luis Enrique; Konigsberg Fainstein, Mina; Bucio, Leticia; Souza, Verónica; Flores, Oscar; Ortíz, Victor; Hernández, Elizabeth; Kershenobich, David; Gutiérrez-Ruíz, María Concepción

    2009-12-01

    Acetaldehyde (Ac), the main metabolite of ethanol oxidation, is a very reactive compound involved in alcohol-induced liver damage. In the present work, we studied the effect of Ac in mitochondria functionality. Mitochondria from Wistar rats were isolated and treated with Ac. Ac decreased respiratory control by 50% which was associated with a decrease in adenosine triphosphate content (28.5%). These results suggested that Ac could be inducing changes in cell redox status. We determined protein oxidation, superoxide dismutase (SOD) activity, and glutathione ratio, indicating that Ac induced an enhanced oxidation of proteins and a decrease in SOD activity (90%) and glutathione/oxidized GSH ratio (36%). The data suggested that Ac-induced oxidative stress mediated by mitochondria dysfunction can lead to cell sensitization and to a second oxidative challenge. We pretreated hepatocytes with Ac followed by treatment with antimycin A, and this experiment revealed a noticeable decrease in cell viability, determined by neutral red assay, in comparison with cells treated with Ac alone. Our data demonstrate that Ac impairs mitochondria functionality generating oxidative stress that sensitizes cells to a second damaging signal contributing to the development of alcoholic liver disease.

  1. 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.

  2. 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.

  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. 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.

  5. 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.

  6. EMLA cream and nitrous oxide to alleviate pain induced by palivizumab (Synagis) intramuscular injections in infants and young children.

    PubMed

    Carbajal, Ricardo; Biran, Valérie; Lenclen, Richard; Epaud, Ralph; Cimerman, Patricia; Thibault, Pascale; Annequin, Daniel; Gold, Francis; Fauroux, Brigitte

    2008-06-01

    Palivizumab (Synagis [Abbot Laboratories, Kent, United Kingdom]) is recommended for the prevention of severe lower respiratory tract infections caused by respiratory syncytial virus in infants at high risk. These injections are very painful, and currently the use of analgesics is not systematic. The objective of this study was to compare the efficacy of EMLA with premixed 50% nitrous oxide/oxygen, used alone or combined with EMLA, for pain alleviation during palivizumab injections. This randomized, double-blind, multicenter study included children who were younger than 24 months. Each child randomly received during the first 3 monthly injections 3 different analgesic interventions: (1) EMLA: application of EMLA plus air inhalation; (2) nitrous oxide/oxygen: inhalation of 50/50 nitrous oxide/oxygen plus application of a placebo cream; and (3) nitrous oxide/oxygen plus EMLA: inhalation of 50/50 nitrous oxide/oxygen plus application of EMLA. Each child was his or her own control. Procedural pain was assessed through videotapes with the Modified Behavioral Pain Scale. The procedure itself was subdivided in 2 periods: (1) injection and (2) recovery (first 30 seconds after the removal of the needle). Modified Behavioral Pain Scale scores over time (injection and recovery periods) and among treatments were compared by repeated-measures analysis of variance. Fifty-five children were included. Mean +/- SD Modified Behavioral Pain Scale pain scores for EMLA, nitrous oxide/oxygen, and nitrous oxide/oxygen plus EMLA were, respectively, 9.3 +/- 1.0, 8.8 +/- 1.2, and 8.2 +/- 1.8 during the injection and 7.8 +/- 1.7, 7.4 +/- 1.9, and 6.9 +/- 2.4 during the recovery period. A significant time and treatment effect in favor of the combined nitrous oxide/oxygen plus EMLA was observed. The administration of 50/50 nitrous oxide/oxygen to infants and young children is effective in decreasing the pain associated with palivizumab intramuscular injections. The combined nitrous oxide

  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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  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. Large-brained birds suffer less oxidative damage.

    PubMed

    Vágási, C I; Vincze, O; Pătraş, L; Osváth, G; Marton, A; Bărbos, L; Sol, D; Pap, P L

    2016-10-01

    Large brains (relative to body size) might confer fitness benefits to animals. Although the putative costs of well-developed brains can constrain the majority of species to modest brain sizes, these costs are still poorly understood. Given that the neural tissue is energetically expensive and demands antioxidants, one potential cost of developing and maintaining large brains is increased oxidative stress ('oxidation exposure' hypothesis). Alternatively, because large-brained species exhibit slow-paced life histories, they are expected to invest more into self-maintenance such as an efficacious antioxidative defence machinery ('oxidation avoidance' hypothesis). We predict decreased antioxidant levels and/or increased oxidative damage in large-brained species in case of oxidation exposure, and the contrary in case of oxidation avoidance. We address these contrasting hypotheses for the first time by means of a phylogenetic comparative approach based on an unprecedented data set of four redox state markers from 85 European bird species. Large-brained birds suffered less oxidative damage to lipids (measured as malondialdehyde levels) and exhibited higher total nonenzymatic antioxidant capacity than small-brained birds, whereas uric acid and glutathione levels were independent of brain size. These results were not altered by potentially confounding variables and did not depend on how relative brain size was quantified. Our findings partially support the 'oxidation avoidance' hypothesis and provide a physiological explanation for the linkage of large brains with slow-paced life histories: reduced oxidative stress of large-brained birds can secure brain functionality and healthy life span, which are integral to their lifetime fitness and slow-paced life history. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Guarding chromosomes from oxidative DNA damage to the very end.

    PubMed

    Tan, Rong; Lan, Li

    2016-07-01

    The ends of each chromosome are capped by the telomere assembly to protect chromosomal integrity from telomere attrition and DNA damage. In response to DNA damage, DNA repair factors are enriched at damage sites by a sophisticated signaling and recruitment cascade. However, DNA damage response at telomeres is different from non-telomeric region of genomic DNA due to specialized sequences and structures of the telomeres. In the course of normal DNA replication or DNA damage repair, both the telomere shelterin protein complex and the condensed telomeric chromatin structure in mammalian cells are modified to protect telomeres from exposing free DNA ends which are subject to both telemere shortening and chromosome end fusion. Initiation of either homologous recombination or non-homologous end joint repair at telomeres requires disassembling and/or post-translational modifications of the shelterin complex and telomeric chromatin. In addition, cancer cells utilize distinct mechanisms to maintain telomere length and cell survival upon damage. In this review, we summarize current studies that focus on telomere end protection and telomere DNA repair using different methodologies to model telomere DNA damage and disruption. These include genetic ablation of sheltering proteins, targeting endonuclease to telomeres, and delivering oxidative damage directly. These different approaches, when combined, offer better understanding of the mechanistic differences in DNA damage response between telomeric and genomic DNA, which will provide new hope to identify potential cancer therapeutic targets to curtail cancer cell proliferation via induction of telomere dysfunctions. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Silymarin alleviates hepatic oxidative stress and protects against metabolic disorders in high-fat diet-fed mice.

    PubMed

    Feng, Bin; Meng, Ran; Huang, Bin; Shen, Shanmei; Bi, Yan; Zhu, Dalong

    2016-01-01

    Silymarin is a potent antioxidant medicine and has been widely used for the treatment of liver diseases over 30 years. Recent studies suggest that silymarin may benefit patients with glucose intolerance. However, the mechanism underlying the action of silymarin is not clarified. The aim of this work was to assess the impact of silymarin on glucose intolerance in high-fat diet (HFD)-fed mice, and explore the potential therapeutic mechanisms. C57BL/6 mice were fed with HFD for 12 weeks, randomized, and treated orally with vehicle saline or silymarin (30 mg/kg) daily for 30 days. We found that silymarin significantly improved HFD-induced body weight gain, glucose intolerance, and insulin resistance in mice. Silymarin treatment reduced HFD-increased oxidative stress indicators (reactive oxygen species, lipid peroxidation, protein oxidation) and restored HFD-down-regulated activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in the plasma and/or liver of the HFD-fed mice. Furthermore, silymarin decreased HFD-up-regulated hepatic NADPH oxidase expression and NF-κB activation in mice. Additionally, silymarin treatment mitigated HFD-increased plasma IL-1β, TNF-α levels, and HFD-enhanced hepatic NO, TLR4, and iNOS expression in mice. These novel data indicate that silymarin has potent anti-diabetic actions through alleviating oxidative stress and inflammatory response, partially by inhibiting hepatic NADPH oxidase expression and the NF-κB signaling.

  17. 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.

  18. Tetramethylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes.

    PubMed

    Gao, Xin; Zhao, Xiao-long; Zhu, Yan-hui; Li, Xiao-mu; Xu, Qiong; Lin, Huan-dong; Wang, Ming-wei

    2011-04-25

    Tetramethylpyrazine (TMP), one of the active ingredients isolated from a Chinese herbal prescription, possesses protective effects against oxidative stress caused by high glucose in endothelial cells. In this study, the role of TMP in preventing muscle cells from palmitate-induced oxidative damage was investigated and the possible mechanisms of action elucidated. Mitochondrial reactive oxygen species (ROS) were measured in C2C12 myotubes, a palmitate-induced oxidative stress cell model, with or without TMP. Both mitochondrial membrane potential (MMP) and oxygen consumption were assessed in conjunction with quantification of mitochondrial DNA and mitochondrial biogenesis-related factors, such as peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam), by real-time polymerase chain reaction. Expression of mitochondrial respiratory chain complex III as an index of mitochondrial function was evaluated by immunoblotting, and glucose transport into the C2C12 myotube examined by analyzing 2-deoxy-[(3)H]glucose uptake. TMP significantly alleviated palmitate-induced mitochondrial ROS production, mitigated mitochondrial dysfunction and increased D-loop mRNA expression as compared with the control. This was accompanied by a marked reversal of palmitate-induced down-regulation in the expression of mitochondrial biogenesis-related factors (PGC1α, NRF1 and Tfam) and decreased glucose uptake in C2C12 myotubes. As a result, cell respiration, as reflected by the elevated expression of mitochondrial respiratory chain complex III and oxygen consumption, was enhanced. TMP is capable of protecting C2C12 myotubes against palmitate-induced oxidative damage and mitochondrial dysfunction, and improving glucose uptake in muscle cells partially through the up-regulation of mitochondrial biogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

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

    PubMed

    Jørgensen, Anders

    2013-07-01

    Both non-pathological psychological stress states and mental disorders are associated with molecular, cellular and epidemiological signs of accelerated aging. Oxidative stress on nucleic acids is a critical component of cellular and organismal aging, and a suggested pathogenic mechanism in several age-related somatic disorders. The overall aim of the PhD project was to investigate the relation between psychopathology, psychological stress, stress hormone secretion and oxidatively generated DNA and RNA damage, as measured by the urinary excretion of markers of whole-body DNA/RNA oxidation (8-oxodG and 8-oxoGuo, respectively). The main hypothesis was that psychological stress states are associated with increased DNA/RNA damage from oxidation. In a study of 40 schizophrenia patients and 40 healthy controls matched for age and gender, we found that 8-oxodG/8-oxoGuo excretion was increased in schizophrenia patients, providing a possible molecular link between schizophrenia and its associated signs of accelerated aging. We found no association between psychopathology, perceived stress or cortisol secretion and 8-oxodG/8-oxoGuo excretion in the patients. In the controls, there were positive correlations between 8-oxodG/8-ocoGuo excretion and 9AM plasma cortisol, but no associations to perceived stress. In an animal study of experimentally induced chronic stress performed in metabolism cages, we found no increase in urinary 8-oxodG/8-oxoGuo or cerebral (hippocampal and frontal cortex) levels of oxidatively generated nucleic acid damage. However, there was a trend towards an increased expression of genes involved in DNA repair, possibly reflecting a compensatory mechanism. In a study of 220 elderly, mostly healthy individuals from the Italian InChianti cohort, we found a significant association between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between

  6. Tyrosine-dependent oxidative DNA damage induced by carcinogenic tetranitromethane.

    PubMed

    Murata, Mariko; Kurimoto, Saori; Kawanishi, Shosuke

    2006-10-01

    Tetranitromethane (TNM) is used as an oxidizer in rocket propellants and explosives and as an additive to increase the cetane number of diesel fuel. TNM was reported to induce pulmonary adenocarcinomas and squamous cell carcinomas in mice and rats. However, the mechanisms underlying carcinogenesis induced by TNM has not yet been clarified. We previously revealed that nitroTyr and nitroTyr-containing peptides caused Cu(II)-dependent DNA damage in the presence of P450 reductase, which is considered to yield nitroreduction. Since TNM is a reagent for nitration of Tyr in proteins and peptides, we have hypothesized that TNM-treated Tyr and Tyr-containing peptides induce DNA damage by the modification of Tyr. We examined DNA damage induced by TNM-treated amino acids or peptides using (32)P-5'-end-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. TNM-treated Tyr and Lys-Tyr-Lys induced DNA damage including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in the presence of Cu(II) and NADH. DNA damage was inhibited by catalase and bathocuproine, indicating the involvement of H(2)O(2) and Cu(I). The cytosine residue of the ACG sequence complementary to codon 273, well-known hotspots of the p53 gene, was cleaved with piperidine and Fpg treatments. On the other hand, nitroTyr and Lys-nitroTyr-Lys did not induce DNA damage in the presence of Cu(II) and NADH. Time-of-flight mass spectrometry confirmed that reactions between Lys-Tyr-Lys and TNM yielded not only Lys-nitroTyr-Lys but also Lys-nitrosoTyr-Lys. Therefore, it is speculated that the nitrosotyrosine residue can induce oxidative DNA damage in the presence of Cu(II) and NADH. It is concluded that Tyr-dependent DNA damage may play an important role in the carcinogenicity of TNM. TNM is a new type of carcinogen that induces DNA damage not by itself but via Tyr modification.

  7. Salidroside alleviates oxidative stress in the liver with non- alcoholic steatohepatitis in rats.

    PubMed

    Yang, Ze-ran; Wang, Hui-fang; Zuo, Tie-cheng; Guan, Li-li; Dai, Ning

    2016-04-14

    Nonalcoholic steatohepatitis (NASH) is characterized by fat accumulation in the hepatocyte, inflammation, liver cell injury, and varying degrees of fibrosis, and can lead to oxidative stress in liver. Here, we investigated whether Salidroside, a natural phenolic antioxidant product, can protect rat from liver injury during NASH. NASH model was established by feeding the male SD rats with high-fat and high-cholesterol diet for 14 weeks. Four groups of male SD rats including, normal diet control group, NASH model group, and Salidroside treatment group with150mg/kg and 300 mg/kg respectively, were studied. Salidroside was given by oral administration to NASH in rats from 9 weeks to 14 weeks. At the end of 14 weeks, liver and serum were harvested, and the liver injury, oxidative stress and histological features were evaluated. NASH rats exhibited significant increases in the following parameters as compared to normal diet control rats: fat droplets with foci of inflammatory cell infiltration in the liver. ALT, AST in serum and TG, TC in hepatocyte elevated. Oxidative responsive genes including CYP2E1 and Nox2 increased. Additionally, NASH model decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to NASH model group, treatment rats with Salidroside effectively reduced lipid accumulation, inhibited liver injury in a does-dependent manner. Salidroside treatment restored antioxidant enzyme levels, inhibited expression of CYP2E1 and Nox2 mRNA in liver, which prevented the initial step of generating free radicals from NASH. The data presented here show that oral administration of Salidroside prevented liver injury in the NASH model, likely through exerting antioxidant actions to suppress oxidative stress and the free radical-generating CYP2E1 enzyme, Nox2 in liver.

  8. 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.

  9. Homologous recombination is required for recovery from oxidative DNA damage.

    PubMed

    Hayashi, Michio; Umezu, Keiko

    2017-04-03

    We have been studying the genetic events, including chromosome loss, chromosome rearrangements and intragenic point mutations, that are responsible for the deletion of a URA3 marker in a loss of heterozygosity (LOH) assay in the yeast Saccharomycess cerevisiae. With this assay, we previously showed that homologous recombination plays an important role in genome maintenance in response to DNA lesions that occur spontaneously in normally growing cells. Here, to investigate DNA lesions capable of triggering homologous recombination, we examined the effects of oxidative stress, a prominent cause of endogenous DNA damage, on LOH events. Treatment of log-phase cells with H2O2 first caused growth arrest and then, during the subsequent recovery, chromosome loss and various chromosome rearrangements were induced more than 10-fold. Further analysis of the rearrangements showed that gene conversion was strongly induced, approximately 100 times more frequently than in untreated cells. Consistent with these results, two diploid strains deficient for homologous recombination, rad52Δ/rad52Δ and rad51Δ/rad51Δ, were sensitive to H2O2 treatment. In addition, chromosome DNA breaks were detected in H2O2-treated cells using pulsed-field gel electrophoresis. Altogether, these results suggest that oxidative stress induced recombinogenic lesions on chromosomes, which then triggered homologous recombination leading to chromosome rearrangements, and that this response contributed to the survival of cells afflicted by oxidative DNA damage. We therefore conclude that homologous recombination is required for the recovery of cells from oxidative stress.

  10. 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.

  11. Plasmalogen phospholipids protect internodal myelin from oxidative damage.

    PubMed

    Luoma, Adrienne M; Kuo, Fonghsu; Cakici, Ozgur; Crowther, Michelle N; Denninger, Andrew R; Avila, Robin L; Brites, Pedro; Kirschner, Daniel A

    2015-07-01

    Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Alleviation effect of arbutin on oxidative stress generated through tyrosinase reaction with l-tyrosine and l-DOPA

    PubMed Central

    2014-01-01

    Background Hydroxyl radical that has the highest reactivity among reactive oxygen species (ROS) is generated through l-tyrosine-tyrosinase reaction. Thus, the melanogenesis might induce oxidative stress in the skin. Arbutin (p-hydroxyphenyl-β-d-glucopyranoside), a well-known tyrosinase inhibitor has been widely used for the purpose of skin whitening. The aim of the present study was to examine if arbutin could suppress the hydroxyl radical generation via tyrosinase reaction with its substrates, l-tyrosine and l-DOPA. Results The hydroxyl radical, which was determined by an electron spin resonance-spin trapping technique, was generated by the addition of not only l-tyrosine but l-DOPA to tyrosinase in a concentration dependent manner. Arbutin could inhibit the hydroxyl radical generation in the both reactions. Conclusion It is presumed that arbutin could alleviate oxidative stress derived from the melanogenic pathway in the skin in addition to its function as a whitening agent in cosmetics. PMID:25297374

  17. 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

  18. Trichosanthes dioica fruit ameliorates experimentally induced arsenic toxicity in male albino rats through the alleviation of oxidative stress.

    PubMed

    Bhattacharya, Sanjib; Haldar, Pallab Kanti

    2012-08-01

    The present work was focused to evaluate the ameliorative property of aqueous extract of Trichosanthes dioica fruit (AQ T. dioica fruit) against arsenic-induced toxicity in male Wistar albino rats. AQ T. dioica fruit was administered orally to rats at 50 and 100 mg/kg body weight for 20 consecutive days prior to oral administration of sodium arsenite (10 mg/kg) for 10 days. Then the rats were sacrificed for the evaluation of body weights, organ weights, hematological profile, serum biochemical profile, and hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA fragmentation. Pretreatment with AQ T. dioica fruit at both doses markedly and significantly normalized body weights, organ weights, hematological profiles, and serum biochemical profile in arsenic-treated animals. Further, AQ T. dioica fruit pretreatment significantly modulated all the aforesaid hepatic and renal biochemical perturbations and reduced DNA fragmentation in arsenic-intoxicated rats. Therefore, from the present findings, it can be concluded that T. dioica fruit possessed remarkable value in amelioration of arsenic-induced hepatic and renal toxicity, mediated by alleviation of arsenic-induced oxidative stress by multiple mechanisms in male albino rats.

  19. β-Elemene attenuates atherosclerosis in apolipoprotein E-deficient mice via restoring NO levels and alleviating oxidative stress.

    PubMed

    Liu, Meng; Chen, Xiaotong; Ma, Ji; Hassan, Waseem; Wu, Huali; Ling, Jiawei; Shang, Jing

    2017-09-25

    β-Elemene is a major bioactive sesquiterpenoids compound isolated from the essential oils of Curcuma Wenyujin, a Chinese medicinal herb that treats tumor in clinics. However anti-atherosclerotic effects of β-elemene have not been fully investigated in vivo. The objective of this study is to further elucidate the anti-atherosclerotic activities of β-elemene in ApoE(-/-) mice. Staining techniques and immunohistochemistry were used to validate atherosclerosis. Serum lipids, plasma nitrite and nitrate were analyzed by colorometric methods. ROS and antioxidative enzymes were measured through kits. Proteome profiler array was performed to analyze atherosclerosis-related inflammatory Cytokine. Western blot was used for measuring various proteins expressions. These results revealed that β-elemene inhibited atherosclerotic lesion size and increased stability of plaques in ApoE(-/-) mice by alleviating levels of vascular oxidative stress and preventing pro-inflammatory cytokine production. In addition β-elemene maintained endothelial function by significantly improving plasma nitrite and nitrate levels and expression of phosphorylation-eNOS in vivo. β-elemene also increased the production of the nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs) and promoted phosphorylation of eNOS(ser1177) and Akt in vitro. In Conclusive, data revealed that β-elemene attenuated atherosclerosis and enhanced stability of plaques at least partially through its antioxidative and anti-inflammatory features and protected against endothelial dysfunction in ApoE(-/-) mice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Role of brassinosteroids in alleviation of phenanthrene–cadmium co-contamination-induced photosynthetic inhibition and oxidative stress in tomato

    PubMed Central

    Ahammed, Golam Jalal; Yu, Jingquan

    2013-01-01

    Heavy metal pollution often occurs together with organic contaminants. Brassinosteroids (BRs) induce plant tolerance to several abiotic stresses, including phenanthrene (PHE) and cadmium (Cd) stress. However, the role of BRs in PHE+Cd co-contamination-induced stress amelioration is unknown. Here, the interactive effects of PHE, Cd, and 24-epibrassinolide (EBR; a biologically active BR) were investigated in tomato plants. The application of Cd (100 µM) alone was more phytotoxic than PHE applied alone (100 µM); however, their combined application resulted in slightly improved photosynthetic activity and pigment content compared with Cd alone after a 40 d exposure. Accumulation of reactive oxygen species and membrane lipid peroxidation were induced by PHE and/or Cd; however, the differences in effect were insignificant between Cd and PHE+Cd. The foliar application of EBR (0.1 µM) to PHE- and/or Cd-stressed plants alleviated photosynthetic inhibition and oxidative stress by causing enhancement of the activity of the enzymes and related transcript levels of the antioxidant system, secondary metabolism, and the xenobiotic detoxification system. Additionally, PHE and/or Cd residues were significantly decreased in both the leaves and roots after application of EBR, more specifically in PHE+Cd-stressed plants when treated with EBR, indicating a possible improvement in detoxification of these pollutants. The findings thus suggest a potential interaction of EBR and PHE for Cd stress alleviation. These results advocate a positive role for EBR in reducing pollutant residues for food safety and also strengthening phytoremediation. PMID:23201830

  1. OXIDANT CONDITIONING PROTECTS CARTILAGE FROM MECHANICALLY-INDUCED DAMAGE

    PubMed Central

    Ramakrishnan, Prem; Hecht, Benjamin; Pedersen, Doug; Lavery, Matthew; Maynard, Jerry; Buckwalter, Joseph; Martin, James

    2013-01-01

    Articular cartilage degeneration in osteoarthritis has been linked to abnormal mechanical stresses that are known to cause chondrocyte apoptosis and metabolic derangement in in vitro models. Evidence implicating oxidative damage as the immediate cause of these harmful effects suggests that the anti-oxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that anti-oxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant pre-conditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses. Porcine cartilage explants were treated every 48 hours with tert-butyl hydrogen peroxide (tBHP) at non-lethal concentrations (25, 100, 250, 500 µM) for a varying number of times (1, 2 or 4) prior to a bout of unconfined axial compression (5 MPa, 1 Hz, 1800 cycles). When compared with untreated controls, tBHP had significant positive effects on post-compression viability, lactate production, and proteoglycan losses. Overall, the most effective regime was 100 µM tBHP applied 4 times. RNA analysis revealed significant effects of 100 µM tBHP on gene expression. Catalase, hypoxia-inducible factor-1alpha (HIF-1α), and glyceraldehyde 6-phosphate dehydrogenase (GAPDH) were significantly increased relative to untreated controls in explants treated 4 times with 100 µM tBHP, a regime that also resulted in a significant decrease in matrix metalloproteinase-3 (MMP-3) expression. These findings demonstrate that repeated exposure of cartilage to sub-lethal concentrations of peroxide can moderate the acute effects of mechanical stress, a conclusion supported by evidence of peroxide-induced changes in gene expression that could render chondrocytes more resistant to oxidative damage. PMID:20058262

  2. 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.

  3. 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.

  4. 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

  5. Oxidative stress from reflux esophagitis to esophageal cancer: the alleviation with antioxidants.

    PubMed

    Song, Ji Hyun; Han, Young-Min; Kim, Won Hee; Park, Jong-Min; Jeong, Migyeong; Go, Eun Jin; Hong, Sung Pyo; Hahm, Ki Baik

    2016-10-01

    The incidence of reflux esophagitis increases in world, affecting approximately 20% of Western populations and its consequent lesion, Barrett's esophagus (BE), established as the primary precursor lesion of esophageal adenocarcinoma (EAC) or Barrett associated adenocarcinoma (BAA), is also increasing in incidence in Asian countries as well as Western countries. The fact that surveillance strategies have not had a major benefit in decreasing the incidence of EAC increased attention to arrest or delay the progression of BE to EAC. Since sustained inflammation and consequent oxidative stress plays core pathogenic role in reflux esophagitis, BE, and BAA, attention paid to anti-inflammatory and antioxidative agents in the treatment of reflux esophagitis. Since the risk of esophagitis is associated with hiatal hernia, body mass index, and duodenogastric reflux, and acid exposure, lifestyle modification and agents to control gastric acidity might be mainstay for treatment, but several studies consistently showed the implication of robust oxidative stress in reflux associated esophageal diseases. In this review article, the pathogenic implication of oxidative stress will be introduced in the development of reflux esophagitis, BE, and EAC. Also, since there is great interest in complete healing of reflux esophagitis and chemoprevention to prevent or slow malignant transformation, the contribution of antioxidants or antioxidative agents, which was delivered during SFRR-Asia 2015 (Chiangmai, Thailand), will be described. Also, the molecular mechanisms how the antioxidative drugs, rebamipide, ecabet sodium, and pantoprazole exerted significant protection from acids or bile acids-associated esophagitis are included.

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

    PubMed

    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.

  7. Huperzine A alleviates neuroinflammation, oxidative stress and improves cognitive function after repetitive traumatic brain injury.

    PubMed

    Mei, Zhengrong; Zheng, Peiying; Tan, Xiangping; Wang, Ying; Situ, Bing

    2017-07-26

    Traumatic brain injury (TBI) may trigger secondary injury cascades including endoplasmic reticulum stress, oxidative stress, and neuroinflammation. Unfortunately, there are no effective treatments targeting either primary or secondary injuries that result in long-term detrimental consequences. Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) that has been used treatment of Alzheimer's disease (AD). This study aimed to explore the neuroprotective effects of HupA in TBI and its possible mechanisms. Repetitive mild closed head injury (CHI) model was used to mimic concussive TBI. Mice were randomly assigned into three groups including sham, vehicle-treated and HupA-treated injured mice. The HupA was given at dose of 1.0 mg/kg/day and was initiated 30 min after the first injury, then administered daily for a total of 30 days. The neuronal functions including motor functions, emotion-like behaviors, learning and memory were tested. Axonal injury, reactive oxygen species (ROS), and neuroinflammation were examined as well. The results showed that injured mice treated with HupA had significant improvement in Morris water maze performance compared with vehicle-treated injured mice. HupA treatment significantly attenuated markers of neuroinflammation and oxidative stress in the injured mice. Taken together, HupA was effective in reducing neuroinflammation, oxidative stress and behavioral recovery after TBI. HupA is a promising candidate for treatment of TBI.

  8. 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

  9. Oxidative damage in young alcohol drinkers: A preliminary study.

    PubMed

    Rendón-Ramírez, Adela; Cortés-Couto, Miriam; Martínez-Rizo, Abril Bernardette; Muñiz-Hernández, Saé; Velázquez-Fernández, Jesús Bernardino

    2013-11-01

    Oxidative damage (OD) biomarkers have been used to evaluate metabolic stress undergone by alcoholic individuals. In alcoholic patients, these biomarkers are usually measured at late stages, i.e., when the alcoholic patients are showing clear signs of impaired hepatic function. OD biomarkers are sensitive indicators of impaired metabolic function, and might be useful in early stages of alcohol consumption to identify individuals who are at greater risk of damage in later stages of alcohol consumption. The aim of the present work was to evaluate some OD biomarkers in young people at early stages of alcohol consumption. The study was carried out in a group of young people (18-23 years old) who drank alcohol, Youngsters Exposed to Alcohol (YEA) with an average intake of 118 g of ethanol/week, and a control group (CG) of non-drinkers. Blood counts, alcohol dehydrogenase (ADH) activity, glutathione peroxidase (GSH-Px) activity, oxidative damage to DNA, and lipid peroxidation were determined in both groups. The anthropometric and blood parameters of both groups were similar and no clinical symptoms of hepatic damage were observed. Nevertheless, ADH activity, lipid peroxidation, and percentage of damaged DNA cells were higher in the YEA group than in the control group. In contrast, GSH-Px activity was lower in the YEA group than in the control group. Alteration in OD biomarkers can be found in individuals with 4-5 years of alcohol drinking history. To our knowledge, this is the first study giving evidence of OD in individuals at early stages of alcohol abuse. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  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. Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy.

    PubMed

    Fourcade, Stéphane; López-Erauskin, Jone; Galino, Jorge; Duval, Carine; Naudi, Alba; Jove, Mariona; Kemp, Stephan; Villarroya, Francesc; Ferrer, Isidre; Pamplona, Reinald; Portero-Otin, Manuel; Pujol, Aurora

    2008-06-15

    X-linked adrenoleukodystrophy (X-ALD) is a fatal neurodegenerative disorder, characterized by progressive cerebral demyelination cerebral childhood adrenoleukodystrophy (CCALD) or spinal cord neurodegeneration (adrenomyeloneuropathy, AMN), adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFA) in tissues. The disease is caused by mutations in the ABCD1 gene, which encodes a peroxisomal transporter that plays a role in the import of VLCFA or VLCFA-CoA into peroxisomes. The Abcd1 knockout mice develop a spinal cord disease that mimics AMN in adult patients, with late onset at 20 months of age. The mechanisms underlying cerebral demyelination or axonal degeneration in spinal cord are unknown. Here, we present evidence by gas chromatography/mass spectrometry that malonaldehyde-lysine, a consequence of lipoxidative damage to proteins, accumulates in the spinal cord of Abcd1 knockout mice as early as 3.5 months of age. At 12 months, Abcd1- mice accumulate additional proteins modified by oxidative damage arising from metal-catalyzed oxidation and glycoxidation/lipoxidation. While we show that VLCFA excess activates enzymatic antioxidant defenses at the protein expression levels, both in neural tissue, in ex vivo organotypic spinal cord slices from Abcd1- mice, and in human ALD fibroblasts, we also demonstrate that the loss of Abcd1 gene function hampers oxidative stress homeostasis. We find that the alpha-tocopherol analog Trolox is able to reverse oxidative lesions in vitro, thus providing therapeutic hope. These results pave the way for the identification of therapeutic targets that could reverse the deregulated response to oxidative stress in X-ALD.

  14. 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

  15. Oxidative guanine base damage regulates human telomerase activity

    PubMed Central

    Fouquerel, Elise; Lormand, Justin; Bose, Arindam; Lee, Hui-Ting; Kim, Grace S.; Li, Jianfeng; Sobol, Robert W.; Freudenthal, Bret D.; Myong, Sua; Opresko, Patricia L.

    2016-01-01

    Changes in telomere length are associated with degenerative diseases and cancer. Oxidative stress and DNA damage have been linked to both positive and negative alterations in telomere length and integrity. Here we examined how the common oxidative lesion 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxoG) regulates telomere elongation by telomerase. When present in the deoxynucleoside triphosphate pool as 8-oxodGTP, telomerase utilization of the oxidized nucleotide during telomere extension is mutagenic and terminates further elongation. Depletion of the enzyme that removes oxidized dNTPs, MTH1, increases telomere dysfunction and cell death in telomerase positive cancer cells harboring shortened telomeres. In contrast, a pre-existing 8-oxoG within the telomeric DNA sequence promotes telomerase activity by destabilizing G-quadruplex structure in the DNA. We show that the mechanism by which 8-oxoG arises in the telomere, either by insertion of oxidized nucleotides or by direct reaction with free radicals, dictates whether telomerase is inhibited or stimulated and thereby, mediates the biological outcome. PMID:27820808

  16. 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

  17. 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

  18. 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.

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

    PubMed

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

    2014-08-12

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

  20. Relationship between indium exposure and oxidative damage in workers in indium tin oxide production plants.

    PubMed

    Liu, Hung-Hsin; Chen, Chang-Yun; Chen, Gun-Ing; Lee, Lien-Hsiung; Chen, Hsiu-Ling

    2012-05-01

    The study aimed to assess the relationship between indium exposure and surfactant protein and any oxidative damage in indium tin oxide (ITO)-exposed workers. The study was conducted in two typical ITO-manufacturing plants in Taiwan. One hundred and seventy manufacturing workers and 132 administrators were recruited. The geometric mean serum indium (S-In) level in the workers of the manufacturing department was 1.26 μg/l, which was significantly higher than those in the administrative department (0.72 μg/l). The S-In levels of 49 workers were higher than 3 μg/l (49/302, 16.2%), exceeding an occupational exposure limit suggested by the Japan Society for Occupational Health. Significant positive relationships were found between S-In and surfactant protein A (SP-A), and surfactant protein D (SP-D) levels. SP-A and SP-D levels were elevated significantly in the workers with moderately high indium exposure. The present study indicates a significant elevating trend of SP-A and SP-D levels in ITO-manufacturing workers, which are sensitive markers of interstitial lung disease. Though the indium exposure is not directly linked to all indicators of oxidative DNA damage, the ITO-manufacturing workplace is suggested to be related to oxidative DNA damage for the workers in the current study. Therefore, in addition to the indium exposure, there might be other occupational hazards in the ITO workplace to cause oxidative damage.

  1. 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).

  2. Taurine attenuates oxidative stress and alleviates cardiac failure in type I diabetic rats

    PubMed Central

    Wang, Guo-guang; Li, Wei; Lu, Xiao-hua; Zhao, Xue; Xu, Lei

    2013-01-01

    Aim To investigate cardioprotective effect of taurine in diabetic rats. Methods Male Sprague-Dawley rats were assigned randomly into four groups of 15 rats: control group, control + taurine group, streptozotocin (STZ) group, and STZ + taurine group. Rats in STZ and STZ+ taurine groups were treated by a single injection of STZ (70 mg kg-1, intraperitoneally) dissolved in 0.01 M citrate buffer (pH 4.5) for induction of diabetes, and rats in control and control + taurine groups were treated with the same volume citrate buffer. Taurine was orally administered to rats in control + taurine and STZ + taurine groups daily for 8 weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) hemodynamic analysis. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA). Myocardial protein kinase B (Akt/PKB) phosphorylation and heme oxygenase-1 (HO-1) protein levels were measured by Western blot in all rats at the end of the study. Results In untreated diabetic rats, LV systolic pressure, rate of pressure rise, and rate of pressure fall were decreased, while LV end-diastolic pressure was increased, indicating reduced LV contractility and slowing of LV relaxation. The levels of Akt/PKB phosphorylation and SOD activity were decreased and HO-1 protein expression and MDA content increased. Taurine treatment significantly improved LV systolic and diastolic function, and there were persistent increases in activities of Akt/PKB and SOD, and the level of HO-1 protein. Conclusion Taurine treatment ameliorates myocardial function and heart oxidant status, while increasing myocardial Akt/PKB phosphorylation, and HO-1 levels have beneficial effects on diabetic cardiomyopathy. PMID:23630144

  3. Puerarin alleviates cognitive impairment and oxidative stress in APP/PS1 transgenic mice.

    PubMed

    Zhou, Yanyan; Xie, Ning; Li, Libo; Zou, Yu; Zhang, Xiaojie; Dong, Miaoxian

    2014-04-01

    Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer's disease (AD). Thus, there is interest in developing antioxidant therapies for the prevention/treatment of cognitive decline during AD. We reported previously that puerarin has antioxidative properties in vitro. Therefore, the aim of the present study was to determine whether puerarin improves cognitive function and reduces oxidative stress in amyloid precursor protein/presenilin-1 (APP/PS1) mice, a well established AD mouse model, and explore its potential mechanism. Our results show that oral administration of puerarin significantly ameliorates cognitive impairment in APP/PS1 mice assessed by the Morris water maze (MWM) test. This was accompanied by a significant decrease in the levels of lipid peroxidation (LPO) through, at least in part, induction of nuclear factor erythroid 2-related factor 2 (Nrf2) target gene heme oxygenase 1 (HO-1) in the hippocampus of APP/PS1 transgenic mice at 9 months of age, but without altering brain Aβ burden. Furthermore, puerarin significantly activated Akt, reduced activation of glycogen synthase kinase 3β (GSK-3β), and induced nuclear translocation of Nrf2 in the hippocampus of APP/PS1 mice but did not alter ERK1/2 phosphorylation. Thus, puerarin may improve cognitive performance in APP/PS1 mice through activation of the Akt/GSK-3β signaling pathway. These findings suggest that puerarin might be an attractive agent for prevention and treatment of cognitive impairment and dementia.

  4. 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.

  5. Manuka honey protects middle-aged rats from oxidative damage

    PubMed Central

    Jubri, Zakiah; Rahim, Noor Baitee Abdul; Aan, Goon Jo

    2013-01-01

    OBJECTIVE: This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats. METHOD: Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively. RESULTS: Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity. CONCLUSIONS: Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status. PMID:24270958

  6. Textile industrial effluent induces mutagenicity and oxidative DNA damage and exploits oxidative stress biomarkers in rats.

    PubMed

    Akhtar, Muhammad Furqan; Ashraf, Muhammad; Anjum, Aftab Ahmad; Javeed, Aqeel; Sharif, Ali; Saleem, Ammara; Akhtar, Bushra

    2016-01-01

    Exposure to complex mixtures like textile effluent poses risks to animal and human health such as mutations, genotoxicity and oxidative damage. Aim of the present study was to quantify metals in industrial effluent and to determine its mutagenic, genotoxic and cytotoxic potential and effects on oxidative stress biomarkers in effluent exposed rats. Metal analysis revealed presence of high amounts of zinc, copper, chromium, iron, arsenic and mercury in industrial effluent. Ames test with/without enzyme activation and MTT assay showed strong association of industrial effluent with mutagenicity and cytotoxicity respectively. In-vitro comet assay revealed evidence of high oxidative DNA damage. When Wistar rats were exposed to industrial effluent in different dilutions for 60 days, then activities of total superoxide dismutase and catalase and hydrogen peroxide concentration were found to be significantly lower in kidney, liver and blood/plasma of effluent exposed rats than control. Vitamin C in a dose of 50 mg/kg/day significantly reduced oxidative effects of effluent in rats. On the basis of this study it is concluded that industrial effluent may cause mutagenicity, in-vitro oxidative stress-related DNA damage and cytotoxicity and may be associated with oxidative stress in rats. Vitamin C may have ameliorating effect when exposed to effluent. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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.

  8. 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

  9. 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

  10. 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.

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

    PubMed

    Sun, Yulong; Zong, Lin; Gao, Zhen; Zhu, Shunxing; Tong, Jian; Cao, Yi

    2017-03-01

    HL-60 cells, derived from human promyelocytic leukemia, were exposed to continuous wave 900MHz radiofrequency fields (RF) at 120μW/cm(2) power intensity for 4h/day for 5 consecutive days to examine whether such exposure is capable damaging the mitochondrial DNA (mtDNA) mediated through the production of reactive oxygen species (ROS). In addition, the effect of RF exposure was examined on 8-hydroxy-2'-dexoyguanosine (8-OHdG) which is a biomarker for oxidative damage and on the mitochondrial synthesis of adenosine triphosphate (ATP) which is the energy required for cellular functions. The results indicated a significant increase in ROS and significant decreases in mitochondrial transcription factor A, mtDNA polymerase gamma, mtDNA transcripts and mtDNA copy number in RF-exposed cells compared with those in sham-exposed control cells. In addition, there was a significant increase in 8-OHdG and a significant decrease in ATP in RF-exposed cells. The response in positive control cells exposed to gamma radiation (GR, which is also known to induce ROS) was similar to those in RF-exposed cells. Thus, the overall data indicated that RF exposure was capable of inducing mtDNA damage mediated through ROS pathway which also induced oxidative damage. Prior-treatment of RF- and GR-exposed the cells with melatonin, a well-known free radical scavenger, reversed the effects observed in RF-exposed cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. 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

  13. 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.

  14. 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

  15. Nitric oxide and hydrogen peroxide alleviate drought stress in marigold explants and promote its adventitious root development.

    PubMed

    Liao, Wei-Biao; Huang, Gao-Bao; Yu, Ji-Hua; Zhang, Mei-Ling

    2012-09-01

    Drought stress is one of the most important environmental factors that regulates plant growth and development. In this study, we examined the effects of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) on adventitious rooting in marigold (Tagetes erecta L.) under drought stress. The results showed that the promoting effect of NO or H(2)O(2) on rooting under drought stress was dose-dependent, with a maximal biological response at 10 μM NO donor sodium nitroprusside (SNP) or 600 μM H(2)O(2). Results also indicated that endogenous NO and H(2)O(2) may play crucial roles in rooting under drought conditions, and H(2)O(2) may be involved in rooting promoted by NO under drought stress. NO or H(2)O(2) treatment attenuated the destruction of mesophyll cells ultrastructure by drought stress. Similarly, NO or H(2)O(2) increased leaf chlorophyll content, chlorophyll fluorescence parameters (Fv/Fm, ΦPS II and qP), and hypocotyls soluble carbohydrate and protein content, while decreasing starch content. Results suggest that the protection of mesophyll cells ultrastructure by NO or H(2)O(2) under drought conditions improves the photosynthetic performance of leaves and alleviates the negative effects of drought on carbohydrate and nitrogen accumulation in explants, thereby adventitious rooting being promoted. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  16. 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. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Socialization alleviates burden of oxidative-stress in hippocampus and prefrontal cortex in morphine addiction period in male rats .

    PubMed

    Famitafreshi, Hamidreza; Karimian, Morteza

    2017-09-19

    Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction of high-risk behaviors can reduce the burden of addiction in society and can improve the overall prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with socialization will reduce occurrence of high-risk behavior during addiction period. Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized, isolated, addicted socialized and addicted isolated. For inducing morphine dependence, rats received morphine (5 mg/rat/kg/day) for 14 days. Socialization was induced by putting two rats in a large cage for 14 days. On the other hand, isolation was induced by putting rats in separate small cages covered with black plastic for the same period. At the end of study, rats were experimented with shuttle box for assessing avoidance memory and also tested with social interaction test to measure novelty-seeking behavior and anxiety level. Then animals were sacrificed for neurochemical analysis. Brain was isolated to assess oxidative-stress (OS) indices such as malondialdehyde (MDA), glutathione and nitrite/nitrate in prefrontal cortex and hippocampus. After 14 days of morphine injection, rats in socialized group had improved avoidance memory, increased anxiety levels and reduced novelty-seeking behavior. Furthermore, isolated rats had reduced glutathione and nitrite/nitrate, and higher MDA levels in prefrontal cortex and hippocampus as compared to socialized rats. Pair state had positive effect on OS indices in prefrontal cortex and hippocampus and results in reduction of relapse and poor prognosis. Thus, OS has an important role for alleviation of severity of addiction period. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. 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.

  5. Alleviation of Rosup-induced oxidative stress in porcine granulosa cells by anthocyanins from red-fleshed apples

    PubMed Central

    He, Guifang; Li, Yapeng; Yang, Leilei; Shen, Wei; Huo, Heqiang; Zhu, Jun; Dai, Hongyi

    2017-01-01

    Anthocyanins are the polyphenolic phytochemicals which have been shown to scavenge free radicals. In this study, we investigated the effects of anthocyanins extracted from red-fleshed apples (Malus sieversii) on reducing oxidative damage by Rosup in porcine granulosa cells (GCs) by measuring intracellular reactive oxygen species (ROS), content of glutathione (GSH), activities of superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPX1) and the gene expression of SOD1, CAT, GPX1. Apoptosis was determined with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and apoptosis-related proteins were quantified with Western blotting. The results indicate that Rosup increases oxidative stress by inducing reactive oxygen species production in porcine GCs and the oxidative stress could be reduced by anthocyanins. The gene expression of SOD1, CAT, GPX1 and the activities of these enzymes were increased when GCs were treated with anthocyanins and Rosup for 6 hours. Anthocyanins inhibit Rosup-induced apoptosis by increasing expression of antiapoptotic protein Bcl-2 and suppressing the expression of pro-apoptotic protein Bax. Collectively, anthocyanins from red-fleshed apples reduce oxidative stress and inhibit apoptosis in porcine GCs in vitro. This approach indicates that antioxidants might be developed from red-fleshed apples. PMID:28850606

  6. 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.

  7. 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

  8. 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

  9. Direct contribution of obesity to oxidative damage to macromolecules.

    PubMed

    Karbownik-Lewinska, Małgorzata; Szosland, Janusz; Kokoszko-Bilska, Agnieszka; Stępniak, Jan; Zasada, Krzysztof; Gesing, Adam; Lewinski, Andrzej

    2012-01-01

    Obesity constitutes a common modifiable risk factor for certain non-communicable diseases (NCDs) associated with enhanced oxidative stress. The aim of the study was to examine serum concentrations of malondialdehyde + 4-hydroxyalkenals (MDA+4-HDA), as an index of lipid peroxidation (LPO), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) concentration in peripheral blood lymphocytes, as an index of nuclear DNA damage, in overweight and obese adult patients. LPO and 8-oxodG, as well as clinical and laboratory parameters, which are frequently affected by obesity, were evaluated in 58 overweight and obese adult patients, and in 20 healthy volunteers. Both LPO and 8-oxodG levels were increased in overweight and obese patients, with further increase observed with the increasing body mass index (BMI). LPO correlated positively with body mass, BMI, waist circumference, hip circumference, waist:hip ratio, systolic or diastolic blood pressure, glucose, C-reactive protein and ferritin concentrations. 8-oxodG correlated positively with body mass, BMI, hip circumference and triglyceride concentration, whereas it correlated negatively with iron concentration. Expectedly, positive correlation between LPO and 8-oxodG was also found. BMI constituted the only independent determinant (predictor) of LPO in overweight and obese patients. Consistently, LPO did constitute the only independent determinant of obesity. Overweight and obesity in adults are directly associated with increased oxidative damage to macromolecules.

  10. Ethylene production is associated with alleviation of cadmium-induced oxidative stress by sulfur in mustard types differing in ethylene sensitivity.

    PubMed

    Asgher, Mohd; Khan, Nafees A; Khan, M Iqbal R; Fatma, Mehar; Masood, Asim

    2014-08-01

    We studied the response of ethylene-sensitive (Pusa Jai Kisan) and ethylene-insensitive (SS2) mustard (Brassica juncea) cultivars to 0, 0.5, 1.0 and 2.0 mM SO₄(2-), and the effect of 1.0 mM SO₄(2-) was studied in the amelioration of 50 µM cadmium (Cd). The Cd-induced oxidative stress and Cd accumulation were greater in SS2 than Pusa Jai Kisan, but sulfur (S) application alleviated Cd-induced oxidative stress more prominently in Pusa Jai Kisan by increasing S-metabolism and synthesis of reduced glutathione (GSH) and ethylene production; and promoted photosynthesis and plant dry mass under Cd stress. The ethylene-sensitive cultivar responded more to S treatment under Cd stress and showed increased activity of antioxidant system resulting in increased photosynthesis and growth. Cadmium treatment resulted in rapid increase in ethylene formation which adversely influenced photosynthesis and plant dry mass. However, S and ethephon application to Cd-treated plants lowered ethylene formation to optimal range responsible for maximal GSH synthesis and protection against Cd-induced oxidative stress. The similarity of the effectiveness of 1.0 mM SO₄(2-) with 200 µL L(-1) ethylene source as ethephon in alleviation of 50 µM Cd further verifies that differential alleviation of Cd toxicity in the two cultivars by S was dependent on ethylene production. The results suggest that ethylene production determines Cd stress alleviation by S via regulatory interaction with antioxidant metabolism. Thus, ethylene production and sensitivity bear a prominent role in alleviation of Cd stress by S and can be used as a criterion for developing Cd tolerant genotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Li-Gan-Shi-Liu-Ba-Wei-San improves non-alcoholic fatty liver disease through enhancing lipid oxidation and alleviating oxidation stress.

    PubMed

    Jiang, Youzhao; Chen, Liu; Wang, Hui; Narisi, Bao; Chen, Bing

    2015-12-24

    Mongolian medicine is an important constituent of traditional Chinese medicine. Its representative prescription, Li-Gan-Shi-Liu-Ba-Wei-San (LGSLBWS), is widely used for long-term treatment of chronic liver disease and nonalcoholic fatty liver disease (NAFLD). This study explored the effects and mechanism of LGSLBWS on NAFLD. NAFLD rat model was established with high-fat diet. The effects of LGSLBWS on lipid metabolism, liver function, and hepatic morphology were observed in NAFLD rats. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver, as well as the expression levels of peroxisome proliferator-activated receptor (PPAR)α, PPARβ, inhibitor of nuclear factor κB α(IκBα), and inducible nitric oxide synthase (iNOS) were all detected. Finally, the effects of LGSLBWS on fatty acid oxidation, PPARα, PPARβ, IκBα, and iNOS were determined in HepG2 cells. LGSLBWS significantly reduced the fat deposition in the liver and the serum aspartate aminotransferase levels in NAFLD rats. Serum triglyceride and free fatty acid levels were reduced by LGSLBWS. Total cholesterol and triglyceride contents in the liver were also downregulated. SOD and MDA levels were increased and decreased by LGSLBWS, respectively. LGSLBWS can significantly promote fatty acid oxidation of HepG2 cells. Upregulation of PPARα, PPARβ, and IκBα and downregulation of iNOS by LGSLBWS were both observed in the NAFLD model and HepG2 cells. LGSLBWS can significantly improve NAFLD by enhancing fatty acid oxidation and alleviating oxidative stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. 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

  13. Oxidative damage of naphthenic acids on the Eisenia fetida earthworm.

    PubMed

    Wang, Jie; Cao, Xiaofeng; Chai, Liwei; Liao, Jingqiu; Huang, Yi; Tang, Xiaoyan

    2016-11-01

    Naphthenic acids (NAs) have been gaining recognition in recent years as potentially harmful environmental contaminants. Few studies have focused on the potential ecotoxicity of NAs to terrestrial environment. In this study, the responses of antioxidant system and lipid peroxidation and DNA damage were investigated after exposing Eisenia fetida to soil contaminated with NAs. The results indicated that NAs induced a significant increase (p < 0.05) in superoxide dismutase and catalase enzyme activities. The glutathione peroxidase enzyme activities were significantly inhibited (p < 0.05) in the medium and high dose treatments. An increase in malondialidehyde indicated that NAs could cause cellular lipid peroxidation in the tested earthworms. The percentage of DNA in the tail of comet assay of coelomocytes as an indication of DNA damage increased after treatment with different doses of NAs, and a dose-dependent DNA damage of coelomocytes was found. In conclusion, oxidative stress caused by NAs exposure induces physiological responses and genotoxicity on earthworms. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1337-1343, 2016. © 2015 Wiley Periodicals, Inc.

  14. DNA photo-oxidative damage hazard in transfection complexes.

    PubMed

    Rudiuk, Sergii; Franceschi-Messant, Sophie; Chouini-Lalanne, Nadia; Perez, Emile; Rico-Lattes, Isabelle

    2011-01-01

    Complexes of DNA with various cationic vectors have been largely used for nonviral transfection, and yet the photochemical stability of DNA in such complexes has never been considered. We studied, for the first time, the influence of DNA complexation by a cationic lipid and polymers on the amount of damage induced by benzophenone photosensitization. The localization of benzophenone inside the hydrophobic domains formed by a cationic lipid, DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride), and close to DNA, locally increases the photoinduced cleavage by the reactive oxygen species generated. The same effect was found in the case of DNA complexation with an amphiphilic polymer (polynorbornenemethyleneammonium chloride). However, a decrease in DNA damage was observed in the case of complexation with a hydrophilic polymer (polyethylenimine). The DNA protection in this case was because of the absence of benzophenone hydrophobic incorporation into the complex, and to DNA compaction which decreased the probability of radical attack. These results underline the importance of the chemical structure of the nonviral transfection vector in limiting the risks of photo-oxidative damage of the complexed DNA. © 2010 The Authors. Photochemistry and Photobiology © 2010 The American Society of Photobiology.

  15. 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

  16. Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats.

    PubMed

    Senthil Kumaran, Vadivel; Arulmathi, Karpagavinayagam; Srividhya, Ravichandran; Kalaiselvi, Periandavan

    2008-03-01

    Ageing is defined as the loss of ability to maintain cellular homeostasis of an organism associated with the free radical-elicited oxidative damage to cellular macromolecules. The aim of this study was to evaluate the efficacy of epigallocatechin-3-gallate (EGCG), the key component of green tea catechins on attenuating the age associated oxidative perturbances by assessing the redox status in mitotic (liver) and post-mitotic (skeletal muscle) tissues of young and aged rats. From the results, we observed an increase in the marker for oxidative damage such as lipid peroxidation and protein carbonyl content in aged rats, when compared to young rats. This was accompanied with decreased levels of both enzymic and non-enzymic antioxidants and redox index. On supplementation with EGCG (100 mg/kg body weight by oral gavage for 30 days), the levels of lipid peroxidation and protein carbonyl content were significantly decreased in aged rats, possibly by enhancing the GSH redox status, and both enzymic and non-enzymic antioxidants status. In conclusion, this study supports the beneficial effect of EGCG in alleviating oxidative disturbances in ageing and retard the age associated derangements in both mitotic and post-mitotic tissues.

  17. 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.

  18. Condensin II Alleviates DNA Damage and Is Essential for Tolerance of Boron Overload Stress in Arabidopsis[W

    PubMed Central

    Sakamoto, Takuya; Inui, Yayoi Tsujimoto; Uraguchi, Shimpei; Yoshizumi, Takeshi; Matsunaga, Sachihiro; Mastui, Minami; Umeda, Masaaki; Fukui, Kiichi; Fujiwara, Toru

    2011-01-01

    Although excess boron (B) is known to negatively affect plant growth, its molecular mechanism of toxicity is unknown. We previously isolated two Arabidopsis thaliana mutants, hypersensitive to excess B (heb1-1 and heb2-1). In this study, we found that HEB1 and HEB2 encode the CAP-G2 and CAP-H2 subunits, respectively, of the condensin II protein complex, which functions in the maintenance of chromosome structure. Growth of Arabidopsis seedlings in medium containing excess B induced expression of condensin II subunit genes. Simultaneous treatment with zeocin, which induces DNA double-strand breaks (DSBs), and aphidicolin, which blocks DNA replication, mimicked the effect of excess B on root growth in the heb mutants. Both excess B and the heb mutations upregulated DSBs and DSB-inducible gene transcription, suggesting that DSBs are a cause of B toxicity and that condensin II reduces the incidence of DSBs. The Arabidopsis T-DNA insertion mutant atr-2, which is sensitive to replication-blocking reagents, was also sensitive to excess B. Taken together, these data suggest that the B toxicity mechanism in plants involves DSBs and possibly replication blocks and that plant condensin II plays a role in DNA damage repair or in protecting the genome from certain genotoxic stressors, particularly excess B. PMID:21917552

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. Intraglandular Transplantation of Adipose-Derived Stem Cells for the Alleviation of Irradiation-Induced Parotid Gland Damage in Miniature Pigs.

    PubMed

    Wang, Zhifa; Ju, Zhaoyu; He, Longlong; Li, Zhijin; Liu, Yanpu; Liu, Bin

    2017-08-01

    In a previous study, the authors verified the protective efficacy of adipose-derived stem cells (ADSCs) on the prevention of salivary gland (SG) damage induced by irradiation in mice. As a critical step before implementation in clinical practice, the present study investigated the protective effect of ADSCs in a miniature pig SG model, because miniature pigs share many characteristics with humans. Third-passage autologous ADSCs at a concentration of 4 × 10(6) cells/mL were transplanted by intraglandular injection into parotid glands (PGs) immediately after local irradiation at a single dose of 20 Gy. The injection process was repeated twice a week for 6 consecutive weeks. At 12 weeks after irradiation, functional and histologic evaluations were performed by measuring salivary flow rate (SFR) and hematoxylin and eosin and periodic acid-Schiff staining. Immunohistochemical and transmission electron microscopic examinations also were conducted to evaluate amylase (AMY) production, microvessel density (MVD), and microstructural changes. The irradiated PGs showed remarkable decreases in SFR, AMY production, and MVD. However, transplantation of ADSCs alleviated irradiated PG morphology and function by preserving more functional acinar cells and increasing SFR and AMY production. In addition, greater MVD was observed in the ADSC-treated group than in the irradiated group. These results indicated that intraglandular transplantation of autologous ADSCs is an effective method to protect PGs against damage from irradiation in miniature pigs, which might have clinic application in the future. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Mitochondria are the main target for oxidative damage in leaves of wheat (Triticum aestivum L.).

    PubMed

    Bartoli, Carlos Guillermo; Gómez, Facundo; Martínez, Dana Ethel; Guiamet, Juan José

    2004-08-01

    Photosynthesis, respiration, and other processes produce reactive oxygen species (ROS) that can cause oxidative modifications to proteins, lipids, and DNA. The production of ROS increases under stress conditions, causing oxidative damage and impairment of normal metabolism. In this work, oxidative damage to various subcellular compartments (i.e. chloroplasts, mitochondria, and peroxisomes) was studied in two cultivars of wheat differing in ascorbic acid content, and growing under good irrigation or drought. In well-watered plants, mitochondria contained 9-28-fold higher concentrations of oxidatively modified proteins than chloroplasts or peroxisomes. In general, oxidative damage to proteins was more intense in the cultivar with the lower content of ascorbic acid, particularly in the chloroplast stroma. Water stress caused a marked increase in oxidative damage to proteins, particularly in mitochondria and peroxisomes. These results indicate that mitochondria are the main target for oxidative damage to proteins under well-irrigated and drought conditions.

  13. Dietary enzymatically treated Artemisia annua L. supplementation alleviates liver oxidative injury of broilers reared under high ambient temperature

    NASA Astrophysics Data System (ADS)

    Wan, Xiaoli; Zhang, Jingfei; He, Jintian; Bai, Kaiwen; Zhang, Lili; Wang, Tian

    2017-03-01

    Heat stress induced by high ambient temperature is a major concern in commercial broiler production. To evaluate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation on growth performance and liver oxidative injury of broilers reared under heat stress, a total of 320 22-day-old male broilers were randomly allotted into five groups with eight replicates of eight birds each. Broilers in the control group were housed at 22 ± 1 °C and fed the basal diet. Broilers in the HS, HS-EA1, HS-EA2, and HS-EA3 groups were fed basal diet supplemented with 0, 0.75, 1.00, and 1.25 g/kg EA, respectively, and reared under cyclic high temperature (34 ± 1 °C for 8 h/day and 22 ± 1 °C for 16 h/day). Broilers fed EA diets had higher final body weight, average daily body weight gain, and average daily feed intake, as well as liver concentration of reduced glutathione, activities of antioxidant enzymes, abilities to inhibit hydroxyl radical and superoxide radical (HS-EA2 and HS-EA3), and lower liver concentrations of reactive oxygen metabolites, malondialdehyde, and protein carbonyl (HS-EA1, HS-EA2, and HS-EA3) than HS group (P < 0.05). EA treatment downregulated the mRNA levels of heat shock proteins 70 and 90, upregulated the mRNA levels of nuclear factor erythroid 2-related factor 2 (HS-EA1, HS-EA2, and HS-EA3) and heme oxygenase 1 (HS-EA2 and HS-EA3) in liver of heat-treated broilers (P < 0.05). In conclusion, EA alleviated heat stress-induced growth depression and liver oxidative injury in broilers, possibly through improving the antioxidant capacity and regulating the pertinent mRNA expression. The appropriate inclusion level of EA in broiler diet is 1.00-1.25 g/kg.

  14. Phenolics from Garcinia mangostana alleviate exaggerated vasoconstriction in metabolic syndrome through direct vasodilatation and nitric oxide generation.

    PubMed

    Abdallah, Hossam M; El-Bassossy, Hany M; Mohamed, Gamal A; El-Halawany, Ali M; Alshali, Khalid Z; Banjar, Zainy M

    2016-09-13

    Exaggerated vasoconstriction plays a very important role in the hypertension, a major component of metabolic syndrome (MetS). In the current work, the potential protective effect of methanol extract of fruit hulls of Garcinia mangostana L. on the exaggerated vasoconstriction in MetS has been investigated. In addition, the bioactive fraction and compounds as well as the possible mechanism of action have been illustrated. The effect of methanol extract of G. mangostana (GMT) fruit hulls on the vascular reactivity of aorta isolated from animals with MetS was investigated through bioassay-guided fractionation procedures. GMT was partitioned with chloroform (I) and the remaining mother liquor was fractionated on a Diaion HP-20 with H2O, 50 and 100 % methanol to give fractions II, III, and IV, respectively. The effect of total extract (GMT), bioactive fraction and the bioactive compounds on the vasoconstriction were examined in aortae isolated from animals with MetS by incubation for 30 min before exposing aortae to cumulative concentrations of phenylephrine (PE). The direct relaxant effect was also examined by adding cumulative concentrations of the bioactive fraction and its bioactive compounds to PE precontracted vessels. In addition, aortic nitric oxide (NO) and reactive oxygen species (ROS) production was investigated. Bioassay-guided fractionation of GMT revealed isolation of garcimangosone D (1), aromadendrin-8-C-β-D-glucopyranoside (2), 2,4,3'-trihydroxy benzophenone-6-O-β-D-glucopyranoside (3), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (4), epicatechin (5), and 2,3',4,5',6-pentahydroxy benzophenone (6). Only compounds 2, 4, and 5 significantly alleviated the exaggerated vasoconstriction of MetS aortae and in the same time showed significant vasodilation of PE pre-contracted aortae. To further illustrate the mechanism of action, the observed vasodilation was completely blocked by the nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl

  15. Dietary enzymatically treated Artemisia annua L. supplementation alleviates liver oxidative injury of broilers reared under high ambient temperature

    NASA Astrophysics Data System (ADS)

    Wan, Xiaoli; Zhang, Jingfei; He, Jintian; Bai, Kaiwen; Zhang, Lili; Wang, Tian

    2017-09-01

    Heat stress induced by high ambient temperature is a major concern in commercial broiler production. To evaluate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation on growth performance and liver oxidative injury of broilers reared under heat stress, a total of 320 22-day-old male broilers were randomly allotted into five groups with eight replicates of eight birds each. Broilers in the control group were housed at 22 ± 1 °C and fed the basal diet. Broilers in the HS, HS-EA1, HS-EA2, and HS-EA3 groups were fed basal diet supplemented with 0, 0.75, 1.00, and 1.25 g/kg EA, respectively, and reared under cyclic high temperature (34 ± 1 °C for 8 h/day and 22 ± 1 °C for 16 h/day). Broilers fed EA diets had higher final body weight, average daily body weight gain, and average daily feed intake, as well as liver concentration of reduced glutathione, activities of antioxidant enzymes, abilities to inhibit hydroxyl radical and superoxide radical (HS-EA2 and HS-EA3), and lower liver concentrations of reactive oxygen metabolites, malondialdehyde, and protein carbonyl (HS-EA1, HS-EA2, and HS-EA3) than HS group ( P < 0.05). EA treatment downregulated the mRNA levels of heat shock proteins 70 and 90, upregulated the mRNA levels of nuclear factor erythroid 2-related factor 2 (HS-EA1, HS-EA2, and HS-EA3) and heme oxygenase 1 (HS-EA2 and HS-EA3) in liver of heat-treated broilers ( P < 0.05). In conclusion, EA alleviated heat stress-induced growth depression and liver oxidative injury in broilers, possibly through improving the antioxidant capacity and regulating the pertinent mRNA expression. The appropriate inclusion level of EA in broiler diet is 1.00-1.25 g/kg.

  16. 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.

  17. Cissus quadrangularis stem alleviates insulin resistance, oxidative injury and fatty liver disease in rats fed high fat plus fructose diet.

    PubMed

    Chidambaram, Jaya; Carani Venkatraman, Anuradha

    2010-01-01

    The study evaluated the protective effects of Cissus quadrangularis stem extract (CQEt) on oxidant-antioxidant balance and insulin resistance (IR) in rats fed high fat-high fructose diet (HFFD) and also tested its free-radical scavenging property in vitro. Rats were fed either control diet or HFFD for 15 days, following which the diet was fortified with CQEt at a dose of 10 g/100g diet. After 60 days, HFFD caused deleterious metabolic effects, including hyperglycemia, IR and liver dysfunction. Rats fed HFFD alone showed increased activities of hepatocellular enzymes in plasma, lipid deposition, significant decline in antioxidants, and elevated lipid peroxidation indices and protein carbonyl in liver. CQEt addition significantly improved insulin sensitivity, reduced liver damage and oxidative changes, and brought back the antioxidants and lipids towards normal. Histopathology of the liver confirmed the changes induced by HFFD and the heptoprotective effect of CQEt. The effects of CQEtin vivo were comparable with that of standard drug, metformin. Through in vitro assays, CQEt was found to contain large quantities of polyphenols, vitamins C and E. CQEt exhibited radical scavenging ability in a dose-dependent manner. These data suggest that CQEt affords hepatoprotection by its antioxidant and insulin-sensitizing activities. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  18. UV-B irradiation alleviates the deterioration of cold-stored mangoes by enhancing endogenous nitric oxide levels.

    PubMed

    Ruan, Jiazhao; Li, Mengya; Jin, Haihong; Sun, Lina; Zhu, Yun; Xu, Maojun; Dong, Jufang

    2015-02-15

    Effects of UV-B radiation on chilling injury, ripening and endogenous nitric oxide (NO) levels in mango fruit were evaluated. Chilling injury index, ion leakage, and malondialdehyde (MDA) content of the fruit pretreated with 5kJm(-2) UV-B for 4h were significantly lower than those of the control during fruit ripening at ambient temperature following cold storage at 6°C for 10days. Fruit firmness of the mangoes irradiated with UV-B was significantly higher than the control during the ripening period. Endogenous NO levels of the UV-B-irradiated fruit were rapidly increased after UV-B treatment. Pre-treatment of mangoes with the NO specific scavenger, not only abolished UV-B-triggered NO accumulation, but also suppressed the UV-B-reduced chilling injury, oxidative damage, and ripening delay of the fruit. Together, the results suggest that UV-B treatment may enhance chilling tolerance and delay fruit ripening of mangoes by triggering endogenous NO generation in the fruit. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. 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.

  20. 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

  1. Lactobacillus plantarum CCFM639 Alleviate Trace Element Imbalance-Related Oxidative Stress in Liver and Kidney of Chronic Aluminum Exposure Mice.

    PubMed

    Yu, Leilei; Zhai, Qixiao; Yin, Ruijie; Li, Peng; Tian, Fengwei; Liu, Xiaoming; Zhao, Jianxin; Gong, Jianhua; Zhang, Hao; Chen, Wei

    2017-04-01

    Aluminum (Al) has various adverse effects on health of humans and animals. The aim of present study was to demonstrate that Lactobacillus plantarum CCFM639 can alleviate the adverse effects on liver and kidney of mice caused by chronic Al exposure. Animals were assigned into control, CCFM639 only, Al only, Al plus CCFM639, and Al plus deferiprone groups. The strain was given by oral gavage for 14 weeks, and Al was introduced via drinking water for the first 8 weeks. Analyses of Al and trace elements levels in feces, blood, and tissues were performed. The biochemical markers (GSH, GPx, SOD, CAT, and MDA) of oxidative stress in livers and kidneys, as well as the levels of ALT, AST, BUN, and CRE in blood, were determined. Our results showed that L. plantarum CCFM639 can significantly reduce Al accumulation in tissues, regulate imbalance of trace elements, and thereby alleviate oxidative stress and pathological changes in hepatic and renal tissues. Therefore, L. plantarum CCFM639 could alleviate Al-induced hepatic and renal injuries, and the possible mechanisms may involve in regulating the imbalance of trace elements.

  2. 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

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

    PubMed

    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.

  4. 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

  5. Alleviation of membrane fouling in a submerged membrane bioreactor with electrochemical oxidation mediated by in-situ free chlorine generation.

    PubMed

    Chung, Chong Min; Tobino, Tomohiro; Cho, Kangwoo; Yamamoto, Kazuo

    2016-06-01

    The control of membrane fouling is still the biggest challenge that membrane bioreactor (MBR) for wastewater treatment faces with. In this report, we evince that an in-situ electrochemical free chlorine generation is effective for membrane fouling mitigation. An electrochemical oxidation (EO) apparatus with perforated Ti/IrO2 anodes and Ti/Pt cathodes was integrated into a conventional MBR with microfiltration module (EO-MBR). The membrane fouling characteristics of EO-MBR fed with synthetic wastewater were monitored for about 2 months in comparison to control MBRs. In the EO-MBR at a direct current density of 0.4 mA/cm(2), the frequency of membrane fouling when the trans-membrane pressure (TMP) reached 30 kPa was effectively reduced by 40% under a physical membrane cleaning regime. The evolution patterns of TMP together with hydraulic resistance analysis based on resistance-in-series model indicated that the electrochemically generated active chlorine alleviated the physically irremovable membrane fouling. Further analysis on extracellular polymeric substances (EPS) of sludge cake layer (SCL) revealed significant reductions of protein contents in soluble EPS and fluorescence emission intensities from humic acids and other fluorophores in bound EPS, which in-turn would decrease the hydrophobic accumulation of organic foulants on membrane pores. The chlorine dosage from the EO apparatus was estimated to be 4.7 mg Cl2/g MLVSS/day and the overall physicochemical properties (bio-solids concentration, floc diameter, zeta-potential) as well as the microbial activity in terms of specific oxygen utilization rate and removal efficiency of dissolved organic carbon (>97%) were not affected significantly. A T-RFLP (terminal restriction fragment length polymorphism) analysis suggested noticeable shifts in microbial community both in mixed liquor and sludge cake layer. Consequently, our electrochemical chlorination would be an efficient fouling control strategy in membrane

  6. 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.

  7. [Observation on the effect of vitamin C in alleviating peroxidative damage in gut of dogs during enteral fluid resuscitation of severe burn shock].

    PubMed

    Hu, Sen; Che, Jin-wei; DU, Ying; Bao, Cheng-mei

    2009-12-01

    To investigate the effect of vitamin C (VC) on alleviating peroxidative damage in gut of dogs during enteral fluid resuscitation of severe burn shock. Eighteen male Beagle dogs were subjected to 50% total body surface area (TBSA) full-thickness burn 24 hours after duodenostomy and cannulation of cervical artery and vein. The dogs were divided into no resuscitation (NR) group (no treatment after burn), enteral resuscitation (ER) group, and ER+VC group according to the random number table, with 6 dogs in each group. Dogs in ER and ER+VC groups were respectively infused with glucose-electrolyte solution (GES) and GES containing 250 mg/kg VC through duodenostomy tube 30 minutes after burn. The infusion rate and volume of GES were in accordance with Parkland formula. Venous blood of dogs was drawn before (0) and at 2, 4, 6, and 8 post burn hours (PBH) to determine the activity of diamine oxidase (DAO) in plasma. Dogs were sacrificed at PBH 8 to collect specimens of jejunum tissue for determining the content of malondialdehyde (MDA), and activity of myeloperoxidase (MPO), xanthine oxidase (XOD) and superoxide dismutase (SOD), and assessment of the water ratio of intestinal tissue by dry-wet weight method. 50% TBSA burn injury resulted in significant elevation of DAO in every group. The activity of DAO in ER group was obviously higher than that in NR group at PBH 6 and 8 (P < 0.05), but DAO activity in ER+VC group was significantly lower than those in the other two groups after PBH 2 (P < 0.05 or P < 0.01). MDA content, MPO and XOD activity and the water ratio of intestinal tissue [(5.74 +/- 0.51) nmol/mg, (2.08 +/- 0.46) U/g, (58.4 +/- 3.8) U/mg, (81.5 +/- 1.8)%] in ER group at PBH 8 was respectively significantly higher than that in NR group [(5.43 +/- 0.25) nmol/mg, (1.55 +/- 0.21) U/g, (50.1 +/- 2.8) U/mg, (78.3 +/- 1.5)%, P < 0.05 or P < 0.01]. While the activity of SOD in ER group (72 +/- 12) U/mg was lower than that in NR group (97 +/- 20) U/mg. MDA content, MPO

  8. 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.

  9. Fructus mume alleviates chronic cerebral hypoperfusion-induced white matter and hippocampal damage via inhibition of inflammation and downregulation of TLR4 and p38 MAPK signaling.

    PubMed

    Lee, Ki Mo; Bang, JiHye; Kim, Bu Yeo; Lee, In Sun; Han, Jung-Soo; Hwang, Bang Yeon; Jeon, Won Kyung

    2015-04-22

    Fructus mume (F. mume) has been used as a traditional medicine for many years in Asian countries. The present study was designed to determine the effect of a 70% ethanol extract of F. mume on white matter and hippocampal damage induced by chronic cerebral hypoperfusion. Permanent bilateral common carotid artery occlusion (BCCAo) was performed on male Wistar rats to induce chronic cerebral hypoperfusion. Daily oral administration of F. mume (200 mg/kg) was initiated 21 days after BCCAo and continued for 42 days. The experimental groups in this study were divided into three groups: a sham-operated group, a BCCAo group, and a BCCAo group that was administered with the F. mume extract. The activation of glial cells, including microglia and astrocytes, and the levels of myelin basic protein (MBP), inflammatory mediators, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and p38 mitogen-activated protein kinase (MAPK) phosphorylation were measured in brains from rats subjected to chronic BCCAo. Our results revealed that F. mume alleviates the reduction in MBP expression caused by chronic BCCAo in the white matter and the hippocampus and significantly attenuates microglial and astrocytic activation induced by chronic BCCAo in the optic tract of white matter. In addition, F. mume treatment reduced the increased expression of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6), as well as the activation of TLR4/MyD88 and p38 MAPK signaling, in the hippocampus of rats subjected to chronic BCCAo. Taken together, our findings demonstrate that brain injury induced by chronic BCCAo is ameliorated by the anti-inflammatory effects of F. mume via inhibition of MBP degradation, microglial and astrocytic activation, increased inflammatory mediator expression, and activated intracellular signalings, including TLR4 and p38 MAPK, implying that F. mume is potentially an effective therapeutics for the treatment of vascular dementia.

  10. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. A study of pyrimidine base damage in relation to oxidative stress and cancer

    PubMed Central

    Iijima, H; Patrzyc, H B; Budzinski, E E; Freund, H G; Dawidzik, J B; Rodabaugh, K J; Box, H C

    2009-01-01

    Background: A long-standing hypothesis is that oxidative stress is a risk factor for cancer. Support for this hypothesis comes from observations of higher levels of oxidative damage in the DNA of WBC of cancer patients compared with healthy controls. Methods: Two generally overlooked types of DNA damage, the formamide modification and the thymine glycol modification, both derived from pyrimidine bases, were assayed as markers of oxidative stress. Damage levels were measured in the DNA of WBC of ovarian cancer patients and of healthy controls. Results: The levels of both modifications were higher in ovarian cancer patients than in healthy controls although in the case of the formamide modification age could not be ruled out as a factor. Conclusion: Our results in combination with other published measurements of oxidative DNA damage support the hypothesis that oxidative damage, on average, is higher in WBC of cancer patients than in healthy controls. PMID:19603029

  12. Enantioselective oxidative damage of chiral pesticide dichlorprop to maize.

    PubMed

    Wu, Tong; Li, Xiuying; Huang, Honglin; Zhang, Shuzhen

    2011-04-27

    To investigate the enantioselective oxidative damage of the pesticide dichlorprop (DCPP) to maize, young seedlings were exposed to solutions of DCPP enantiomers and racemate at different concentrations. Early root development was more influenced by (R)-DCPP than racemic (rac)- and (S)-DCPP. Inhibition rates of seed germination, seedling biomass, and root and shoot elongation were all in the order of (R)-DCPP > (rac)-DCPP > (S)-DCPP treatments. The antioxidant enzyme activities of superoxide dismutase (SOD) and peroxidase (POD) were significantly upregulated by exposure to lower concentrations of (R)-DCPP than (rac)- and (S)-DCPP. Direct determination of the formation of hydroxyl radical (•OH) with electron paramagnetic resonance (EPR) spectroscopy indicated that the •OH level in maize roots followed the order of (R)-DCPP > (rac)-DCPP > (S)-DCPP treatments. All of these results provide solicited evidence of the significant enantioselective phytotoxicity of DCPP to maize with a higher toxicity of (R)-DCPP than (S)- and (rac)-DCPP.

  13. 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

  14. 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.

  15. Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage

    SciTech Connect

    Samuni, A.; Winkelsberg, D.; Pinson, A.; Hahn, S.M.; Mitchell, J.B.; Russo, A. )

    1991-05-01

    The protective effect of stable nitroxide radicals against oxidative damage was studied using cardiomyocyte cultures obtained from newborn rats. Monolayered cardiomyocytes were exposed to H{sub 2}O{sub 2} and the effect on spontaneous beating and leakage of LDH was determined. Hydrogen peroxide irreversibly blocked rhythmic beating and resulted in a significant membrane injury as shown by release of LDH. The injury was prevented by catalase which removes H{sub 2}O{sub 2} and by cell-permeable, metal-chelating agents such as desferrioxamine or bipyridine. In contrast, reagents which are excluded from the cell such as superoxide dismutase or DTPA did not protect the cells against H{sub 2}O{sub 2}. Five- and six-membered ring, stable nitroxide radicals which have previously been shown to chemically act as low-molecular weight, membrane-permeable, SOD-mimetic compounds provided full protection. The nitroxides prevented leakage of LDH and preserved normal cardiomyocyte contractility, presumably by intercepting intracellular O{sub 2}-radicals. Alternatively, protection may result through nitroxides reacting with reduced transition metal ions or by detoxifying secondary organic radicals.

  16. 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

  17. 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.

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

    PubMed Central

    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. PMID:27057276

  19. Gentamicin induced nitric oxide-related oxidative damages on vestibular afferents in the guinea pig.

    PubMed

    Hong, Sung Hwa; Park, Sook Kyung; Cho, Yang-Sun; Lee, Hyun-Seok; Kim, Ki Ryung; Kim, Myung Gu; Chung, Won-Ho

    2006-01-01

    Gentamicin is a well-known ototoxic aminoglycoside. However, the mechanism underlying this ototoxicity remains unclear. One of the mechanisms which may be responsible for this ototoxicity is excitotoxic damage to hair cells. The overstimulation of the N-methyl-d-aspartate (NMDA) receptors increases the production of nitric oxide (NO), which induces oxidative stress on hair cells. In order to determine the mechanism underlying this excitotoxicity, we treated guinea pigs with gentamicin by placing gentamicin (0.5 mg) pellets into a round window niche. After the sacrifice of the animals, which occurred at 3, 7 and 14 days after the treatment, the numbers of hair cells in the animals were counted with a scanning electron microscope. We then performed immunostaining using neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS) and nitrotyrosine antibodies. The number of hair cells in the animals was found to decrease significantly after 7 days. nNOS and iNOS expression levels were observed to have increased 3 days after treatment. Nitrotyrosine was expressed primarily at the calyceal afferents of the type I hair cells 3 days after treatment. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining revealed positive hair cells 3 days after treatment. Our results suggest that inner ear treatment with gentamicin may upregulate nNOS and iNOS to induce oxidative stress in the calyceal afferents of type I hair cells, via nitric oxide overproduction.

  20. 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.

  1. 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

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

    PubMed Central

    Colombo, N.B.R.; Rangel, M.P.; Martins, V.; Hage, M.; Gelain, D.P.; Barbeiro, D.F.; Grisolia, C.K.; Parra, E.R.; Capelozzi, V.L.

    2015-01-01

    The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress. PMID:26200231

  3. 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.

  4. Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP-1 and activation of Nrf2-ARE antioxidant system.

    PubMed

    Sun, Zhengwang; Park, Sang Yong; Hwang, Eunson; Zhang, Mengyang; Seo, Seul A; Lin, Pei; Yi, Tae-Hoo

    2017-02-01

    Solar ultraviolet (UV) radiation-induced reactive oxidative species is mainly responsible for the development of photoageing. Rosmarinic acid was one of the main bioactive components detected in Thymus vulgaris (TV) we extracted. In this study, UVB-induced skin damages have been shown to be ameliorated by treatment with TV in hairless mice (HR-1) skin, demonstrated by decreased matrix metalloproteinases (MMPs) and increased collagen production. However, the underlying molecular mechanism on which TV acted was unclear. We examined the photoprotective effects of TV against UVB and elucidated the molecular mechanism in normal human dermal fibroblasts. Thymus vulgaris remarkably prevented the UVB-induced reactive oxygen species and lactate dehydrogenase. Dose-dependent increase in glutathione, NAD(P)H: quinone oxidoreductase1 and heme oxygenase-1, by TV was confirmed by increased nuclear accumulation of Nrf2. Furthermore, 5-Methoxyindole-2-carboxylic acid was introduced as a specific inhibitor of dihydrolipoyl dehydrogenase (DLD). We demonstrated that Nrf2 expression was regulated by DLD, which was a tricarboxylic acid cycle-associated protein that decreased after UVB exposure. Besides, TV significantly diminished UVB induced phosphorylation of mitogen activated protein kinases pathway, containing extracellular signal-regulated kinase, Jun N-terminal kinase and p38, which consequently reduced phosphorylated c-fos and c-jun. Our results suggest that TV is a potential botanical agent for use against UV radiation-induced oxidative stress mediated skin damages. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  5. 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.

  6. 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.

  7. Preliminary evaluation of a model of stimulant use, oxidative damage, and executive dysfunction

    PubMed Central

    Winhusen, Theresa; Walker, Jessica; Brigham, Gregory; Lewis, Daniel; Somoza, Eugene; Theobald, Jeff; Somoza, Veronika

    2014-01-01

    Background Illicit stimulant use increases oxidative stress and oxidative stress has been found to be associated with deficits in memory, attention, and problem-solving. Objective To test a model of the association among oxidative DNA damage, a severe form of oxidative stress, and stimulant use, executive function, and stimulant-use outcomes. Methods Six sites evaluating 12-step facilitation for stimulant abusers obtained peripheral blood samples from methamphetamine-dependent (n=45) and cocaine-dependent (n=120) participants. The blood samples were submitted to a comet assay to assess oxidative DNA damage. Executive Dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), which is a reliable and valid self-report assessment of executive dysfunction, disinhibition, and apathy. Stimulant-use measures included self-reported stimulant use and stimulant urine drug screens (UDS). Results While more recent cocaine use (<30 days abstinence) was associated with greater oxidative DNA damage (W=2.4, p<.05, d=.36), the results did not support the hypothesized relationship between oxidative DNA damage, executive dysfunction, and stimulant-use outcomes for cocaine-dependent patients. Support for the model was found for methamphetamine-dependent patients, with oxidative DNA damage significantly greater in methamphetamine-dependent patients with executive dysfunction (W=2.2, p<.05, d=.64) and with executive dysfunction being a significant mediator of oxidative DNA damage and stimulant use during active treatment (ab=0.089, p<.05). As predicted, neither disinhibition nor apathy were significant mediators of oxidative damage and future stimulant use. Conclusion These findings provide preliminary support for a model in which oxidative damage resulting from methamphetamine use results in executive dysfunction which in turn increases vulnerability to future stimulant use. PMID:23808868

  8. Magnesium sulfate affords protection against oxidative damage during severe preeclampsia.

    PubMed

    Abad, C; Vargas, F R; Zoltan, T; Proverbio, T; Piñero, S; Proverbio, F; Marín, R

    2015-02-01

    MgSO4 is the drug of choice to prevent seizures in preeclamptic pregnant women, but its mechanism of action at the molecular level remains an enigma. In previous works, we found that treating preeclamptic women with MgSO4 reduces the lipid peroxidation of their red blood cell membranes to normal levels and leads to a significant reduction in the osmotic fragility of the red blood cells that is increased during preeclampsia. In addition, the increase in lipid peroxidation of red cell membranes induced by the Fenton reaction does not occur when MgSO4 is present. The antioxidant protection of MgSO4 was evaluated in UV-C-treated red blood cell ghosts and syncytiotrophoblast plasma membranes by measuring their level of lipid peroxidation. The interaction of MgSO4 with free radicals was assessed for its association with the galvinoxyl radical, the quenching of H2O2-induced chemiluminescence and its effect on sensitized peroxidation of linoleic acid. a) MgSO4 protected red blood cell ghosts and the syncytiotrophoblast plasma membranes of normotensive pregnant women against lipid peroxidation induced by UV-C irradiation. b) MgSO4 does not seem to scavenge the galvinoxyl free radical. c) The quenching of the H2O2-enhanced luminol chemiluminescence is increased by the presence of MgSO4. d) The peroxidation of linoleic acid is significantly blocked by MgSO4. MgSO4 may provide protection against oxidative damage of plasma membranes through interactions with alkyl radicals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 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.

  10. 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.

  11. 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.

  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. [Role of rotenone in mitochondrial oxidative damage and the underlying mechanisms].

    PubMed

    Deng, Yong; Lu, Jun

    2014-10-01

    Rotenone is one of the typical inhibitors of the complex I on the mitochondrial respiratory chain. Numerous studies showed when applied to live animals or cells, rotenone could lead to mitochondrial dysfunction, ROS augment, and thus oxidative damage to proteins, lipids and nucleic acids. Through exploring the process of ROS generation in mitochondria, the relationship between rotenone and mitochondrial ROS generation and the role of rotenone in DNA damage, we elucidated the mechanisms of rotenone induced-mitochondrial oxidative damage. At the same time, we attempted to explore the mtDNA damage and the mutation induced by rotenone.

  14. 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.

  15. 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

  16. 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.

  17. [The effects of oxidative damage induced by organic oxidant t-BHP on cochlear hair cells].

    PubMed

    Chen, Li-mei; Guo, Xiao; Li, Xu-dong; Wang, Zhi; Liu, Yi-min

    2012-03-01

    To establish the oxidative damage model of cochlea hair cells using organic oxidant t-BHP in vitro. HEI-OC1 cells were exposed to t-BHP at 8 doses (30~4000 µmol/L) for 12 h. Trypan blue test was used to detected the cellular viability and MTT assay was utilized to measured the cellular proliferation. The intracellular ROS levels were determined by 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA). The survival rates of HEI-OC1 cells started decrease significantly at the dose of 100 µmol/L t-BHP, the peak of decreased survival rates appeared at the doses of 200~800 µmol/L. The results of MTT assay demonstrated that 30 µmol/L t-BHP could promote cellular proliferation ability, when t-BHP concentrations were higher than 200 µmol/L, the cellular proliferation ability was inhibited. The results of DCFH-DA assay showed that there was no fluorescence in control group, the strong fluorescence was observed in positive control group, the weak fluorescence was observed in 30~50 µmol/L t-BHP groups, the bright fluorescence was observed in 100 µmol/L t-BHP group, still the stronger fluorescence was observed in 200~1000 µmol/L groups, but the cellular number decreased with the doses because of the lower cellular viability. The exposure to 100 µmol/L t-BHP for 12 h could simulate the oxidative damage induced by noise in cochlear hair cells.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. Black tea extract supplementation decreases oxidative damage in Jurkat T cells.

    PubMed

    Erba, D; Riso, P; Foti, P; Frigerio, F; Criscuoli, F; Testolin, G

    2003-08-15

    The purpose of this study was to investigate the protective effect of black tea (BT) extract against induced oxidative damage in Jurkat T-cell line. Cells supplemented with 10 or 25 mg/L BT were subjected to oxidation with ferrous ions. Malondialdehyde (MDA) production as marker of lipid peroxidation, DNA single strand breaks as marker of DNA damage, and modification of the antioxidant enzyme activity, glutathione peroxidase (GPX) were measured. Results show the efficacy of BT polyphenols to decrease DNA oxidative damage and to affect GPX activity (P<0.05), while no effect was shown on MDA production. The succeeding investigation of the activity of caffeine and epigallocatechin gallate demonstrated their antioxidant potential with respect to the cellular markers evaluated. In conclusion, this study supports the protective effect of BT against ferrous ions induced oxidative damage to DNA and the ability of BT to affect the enzyme antioxidant system of Jurkat cells.

  6. Oxidative damage increases with reproductive energy expenditure and is reduced by food-supplementation

    PubMed Central

    Fletcher, Quinn E.; Selman, Colin; Boutin, Stan; McAdam, Andrew G.; Woods, Sarah B.; Seo, Arnold Y.; Leeuwenburgh, Christiaan; Speakman, John R.; Humphries, Murray M.

    2013-01-01

    A central principle in life-history theory is that reproductive effort negatively affects survival. Costs of reproduction are thought to be physiologically-based, but the underlying mechanisms remain poorly understood. Using female North American red squirrels (Tamiasciurus hudsonicus), we test the hypothesis that energetic investment in reproduction overwhelms investment in antioxidant protection, leading to oxidative damage. In support of this hypothesis we found that the highest levels of plasma protein oxidative damage in squirrels occurred during the energetically-demanding period of lactation. Moreover, plasma protein oxidative damage was also elevated in squirrels that expended the most energy and had the lowest antioxidant protection. Finally, we found that squirrels that were food-supplemented during lactation and winter had increased antioxidant protection and reduced plasma protein oxidative damage providing the first experimental evidence in the wild that access to abundant resources can reduce this physiological cost. PMID:23617928

  7. 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...

  8. 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.

  9. 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.

  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 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

  12. Alcoholic beverages and gastric epithelial cell viability: effect on oxidative stress-induced damage.

    PubMed

    Loguercio, C; Tuccillo, C; Federico, A; Fogliano, V; Del Vecchio Blanco, C; Romano, M

    2009-12-01

    Alcohol is known to cause damage to the gastric epithelium independently of gastric acid secretion. Different alcoholic beverages exert different damaging effects in the stomach. However, this has not been systematically evaluated. Moreover, it is not known whether the non-alcoholic components of alcoholic beverages also play a role in the pathogenesis of gastric epithelial cell damage. Therefore, this study was designed to evaluate whether different alcoholic beverages, at a similar ethanol concentration, exerted different damaging effect in gastric epithelial cells in vitro. Moreover, we evaluated whether pre-treatment of gastric epithelial cells with alcoholic beverages prevented oxidative stress-induced damage to gastric cells. Cell damage was assessed, in MKN-28 gastric epithelial cells, by MTT assay. Oxidative stress was induced by incubating cells with xanthine and xanthine oxidase. Gastric cell viability was assessed following 30, 60, and 120 minutes incubation with ethanol 17.5-125 mg/ml(-1) or different alcoholic beverages (i.e., beer, white wine, red wine, spirits) at comparable ethanol concentration. Finally, we assessed whether pre-incubation with red wine (with or without ethanol) prevented oxidative stress-induced cell damage. Red wine caused less damage to gastric epithelial cells in vitro compared with other alcoholic beverages at comparable ethanol concentration. Pre-treatment with red wine, but not with dealcoholate red wine, significantly and time-dependently prevented oxidative stress-induced cell damage. 1) red wine is less harmful to gastric epithelial cells than other alcoholic beverages; 2) this seems related to the non-alcoholic components of red wine, because other alcoholic beverages with comparable ethanol concentration exerted more damage than red wine; 3) red wine prevents oxidative stress-induced cell damage and this seems to be related to its ethanol content.

  13. Cellular and molecular damage of Phanerochaete chrysosporium by the oxidation hair dyes.

    PubMed

    Xiong, Hongxia; Zhou, Qixing

    2012-07-01

    The toxic effect of the oxidation hair dyes on Phanerochaete chrysosporium was investigated by exposure of this fungus in a nitrogen-limited culture medium to various concentrations of the oxidation hair dyes. The results showed that both the size and the dry weight of the mycelial pellets of P. chrysosporium could be reduced when the concentration of the oxidation hair dyes was higher than 300 mg/L. By using the AFLP analysis and the UPGMA dendrogram, the DNA damage of P. chrysosporium by the oxidation hair dyes was also detected. Comparing with that in the control, the percent polymorphism under different concentrations of the oxidation hair dyes increased. In the meantime, the DNA similarity was decreased, which meant that the DNA damage was aggravated with an increase in the concentrations of the oxidation hair dyes. Thus, as an environmental pollutant, the oxidation hair dyes have a toxic effect on P. chrysosporium at both cellular and molecular levels.

  14. 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.

  15. The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression.

    PubMed

    Czarny, Piotr; Wigner, Paulina; Galecki, Piotr; Sliwinski, Tomasz

    2017-06-29

    A growing body of evidence suggests that inflammation, mitochondrial dysfunction and oxidant-antioxidant imbalance may play a significant role in the development and progression of depression. Elevated levels of reactive oxygen and nitrogen species - a result of oxidant-antioxidant imbalance - may lead to increased damage of biomolecules, including DNA. This was confirmed in depressed patients in a research study conducted by our team and other scientists. 8-oxoguanine - a marker of oxidative DNA damage - was found in the patients' lymphocytes, urine and serum. These results were confirmed using a comet assay on lymphocytes. Furthermore, it was shown that the patients' cells repaired peroxide-induced DNA damage less efficiently than controls' cells and that some single nucleotide polymorphisms (SNP) of the genes involved in oxidative DNA damage repair may modulate the risk of depression. Lastly, less efficient DNA damage repair observed in the patients can be, at least partly, attributed to the presence of specific SNP variants, as it was revealed through a genotype-phenotype analysis. In conclusion, the available literature shows that both oxidative stress and less efficient DNA damage repair may lead to increased DNA damage in depressed patients. A similar mechanism may result in mitochondrial dysfunction, which is observed in depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 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...

  17. 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.

  18. 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...

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats

    PubMed Central

    Sun, Wenyan; Yan, Chunhong; Frost, Bess; Wang, Xin; Hou, Chen; Zeng, Mengqi; Gao, Hongli; Kang, Yuming; Liu, Jiankang

    2016-01-01

    High blood pressure, or “hypertension,” is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension. PMID:27713551

  4. 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.

  5. 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. © 2015 Poultry Science Association Inc.

  6. 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

  7. Specialty supplement use and biologic measures of oxidative stress and DNA damage

    PubMed Central

    Kantor, Elizabeth D.; Ulrich, Cornelia M.; Owen, Robert W.; Schmezer, Peter; Neuhouser, Marian L.; Lampe, Johanna W.; Peters, Ulrike; Shen, Danny D.; Vaughan, Thomas L.; White, Emily

    2013-01-01

    Background Oxidative stress and resulting cellular damage have been suggested to play a role in the etiology of several chronic diseases, including cancer and cardiovascular disease. Identifying factors associated with reduced oxidative stress and resulting damage may guide future disease-prevention strategies. Methods In the VITamins And Lifestyle (VITAL) biomarker-study of 209 persons living in the Seattle area, we examined the association between current use of several specialty supplements and oxidative stress, DNA damage, and DNA repair capacity. Use of glucosamine, chondroitin, fish oil, methylsulfonylmethane (MSM), co-enzyme Q10 (CoQ10), ginseng, ginkgo, and saw palmetto was ascertained by a supplement inventory/interview, while use of fiber supplements was ascertained by questionnaire. Supplements used by more than 30 persons (glucosamine and chondroitin) were evaluated as the trend across number of pills/week (non-use, <14 pills/week, 14+ pills/week), while less-commonly used supplements were evaluated as use/non-use. Oxidative stress was measured by urinary 8-isoprostane and PGF2α concentrations using enzyme immunoassays (EIA), while lymphocyte DNA damage and DNA repair capacity were measured using the Comet assay. Multivariate-adjusted linear regression was used to model the associations between supplement use and oxidative stress/DNA damage. Results Use of glucosamine (p-trend:0.01), chondroitin (p-trend:0.003), and fiber supplements (p:0.01) was associated with reduced PGF2α concentrations, while CoQ10 supplementation was associated with reduced baseline DNA damage (p:0.003). Conclusions Use of certain specialty supplements may be associated with reduced oxidative stress and DNA damage. Impact Further research is needed to evaluate the association between specialty supplement use and markers of oxidative stress and DNA damage. PMID:23917455

  8. Anti-oxidant enzyme activities and expression and oxidative damage in patients with non-immediate reactions to drugs

    PubMed Central

    Cornejo-Garcia, J A; Mayorga, C; Torres, M J; Fernandez, T D; R-Pena, R; Bravo, I; Mates, J M; Blanca, M

    2006-01-01

    Adverse drug reactions with an immunological basis (ADRIB) may involve activation of other concomitant, non-specific mechanisms, amplifying the specific response and contributing to the severity and duration. One concomitant mechanism could be the generation of reactive oxygen species (ROS) and/or their detoxification by anti-oxidants, including anti-oxidant enzymes. We analysed the activity of the anti-oxidant enzymes Cu/Zn-superoxide dismutase (SOD), catalase (CAT) and cellular glutathione peroxidase (GPX), as well as certain markers of oxidative damage (thiobarbituric acid reactive substances (TBARS) and carbonyl content) in peripheral blood mononuclear cells from patients with non-immediate ADRIB using spectrophotometric methods and the anti-oxidant enzymes expression by quantitative real-time reverse transcription–polymerase chain reaction. SOD activity and expression were increased in all types of non-immediate reactions (urticaria, maculopapular exanthema and toxic epidermal necrolysis). Regarding oxidative damage, TBARS were increased in urticaria and maculopapular exanthema, and carbonyl groups in all types of reactions. Our observations indicate that oxidative damage occurs in non-immediate reactions. Carbonyl stress and the inadequacy of the anti-oxidant defences are probable causes. PMID:16879248

  9. Anti-oxidant enzyme activities and expression and oxidative damage in patients with non-immediate reactions to drugs.

    PubMed

    Cornejo-Garcia, J A; Mayorga, C; Torres, M J; Fernandez, T D; R-Pena, R; Bravo, I; Mates, J M; Blanca, M

    2006-08-01

    Adverse drug reactions with an immunological basis (ADRIB) may involve activation of other concomitant, non-specific mechanisms, amplifying the specific response and contributing to the severity and duration. One concomitant mechanism could be the generation of reactive oxygen species (ROS) and/or their detoxification by anti-oxidants, including anti-oxidant enzymes. We analysed the activity of the anti-oxidant enzymes Cu/Zn-superoxide dismutase (SOD), catalase (CAT) and cellular glutathione peroxidase (GPX), as well as certain markers of oxidative damage (thiobarbituric acid reactive substances (TBARS) and carbonyl content) in peripheral blood mononuclear cells from patients with non-immediate ADRIB using spectrophotometric methods and the anti-oxidant enzymes expression by quantitative real-time reverse transcription-polymerase chain reaction. SOD activity and expression were increased in all types of non-immediate reactions (urticaria, maculopapular exanthema and toxic epidermal necrolysis). Regarding oxidative damage, TBARS were increased in urticaria and maculopapular exanthema, and carbonyl groups in all types of reactions. Our observations indicate that oxidative damage occurs in non-immediate reactions. Carbonyl stress and the inadequacy of the anti-oxidant defences are probable causes.

  10. Anti-oxidative effects of safranal on immobilization-induced oxidative damage in rat brain.

    PubMed

    Samarghandian, Saeed; Samini, Fariborz; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    2017-09-01

    Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. The present study was designed to investigate the effects of safranal against restraint stress induced oxidative damage in the rat brain. For inducing the chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days, then, the animals received systemic administrations of vehicle (0.1% DMSO) acted as the control group or safranal daily for 21days. Results indicated that the rats submitted to restraint stress showed an increase in the immobility time versus the non-stress rats. In addition, stress decreased number of crossing in the rats submitted to restraint stress versus the non-stress animals. Treatment with safranal (0.75mg/kg) showed a significant reduction in the immobility time compared to the non-treated stress group, while, the treatment improved the number of crossing in rats submitted to restraint stress versus the vehicle-treated stress rats. In the stressed animals that received vehicle, the MDA level was significantly higher and the levels of GSH and antioxidant enzymes were significantly lower than the non-stressed rats. Safranal ameliorated the changes in the stressed animals as compared with the control groups. The present findings indicate that safranal might be effective against depressant-like effects induced by chronic stress via modulating brain oxidative response. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Effect of low and high temperature anneal on process-induced damage of gate oxide

    SciTech Connect

    King, J.C.; Hu, C. . Dept. of Electrical Engineering and Computer Sciences)

    1994-11-01

    The authors have investigated the ability of high and low temperature anneals to repair the gate oxide damage due to simulated electrical stress caused by wafer charging resulting from plasma etching, etc. Even 800 C anneal cannot restore the stability in interface trap generation. Even 900 C anneal cannot repair the deteriorated charge-to-breakdown and oxide charge trapping. As a small consolation, the ineffectiveness of anneal in repairing the process-induced damage allows them to monitor the damages even at the end of the fabrication process.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells.

    PubMed

    Dun, Yun-lou; Zhou, Xiao-lin; Guan, Hua-shi; Yu, Guang-li; Li, Chun-xia; Hu, Ting; Zhao, Xia; Cheng, Xiao-lei; He, Xiao-xi; Hao, Jie-jie

    2015-09-01

    Muscle wasting is associated with a variety of chronic or inflammatory disorders. Evidence suggests that inflammatory cytokines play a vital role in muscle inflammatory pathology and this may result in oxidative damage and mitochondrial dysfunction in skeletal muscle. In our study, we used microwave degradation to prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells induced by tumor necrosis factor alpha (TNF-α), a cell inflammatory cytokine. The results indicated that LMG could alleviate mitochondrial reactive oxygen species (ROS) production, increase the activities of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential (MMP) and upregulate the expression of mitochondrial respiratory chain protein in TNF-α-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-α-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-κB) signaling pathway. These suggest that LMG is capable of protecting TNF-α-induced C2C12 cells against oxidative damage and mitochondrial dysfunction.

  17. 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

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

    PubMed

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

    2010-09-01

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

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

    PubMed Central

    Sahhugi, Zulaikha; Jubri, Zakiah

    2014-01-01

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

  20. 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.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2014-01-01

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

  3. 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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. 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

  5. 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.

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

    PubMed Central

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

    2012-01-01

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

  7. [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.

  8. Selective A2A receptor antagonist SCH 58261 modulates striatal oxidative stress and alleviates toxicity induced by 3-Nitropropionic acid in male Wistar rats.

    PubMed

    Bortolatto, Cristiani F; Reis, Angélica S; Pinz, Mikaela P; Voss, Guilherme T; Oliveira, Renata L; Vogt, Ane G; Roman, Silvane; Jesse, Cristiano R; Luchese, Cristiane; Wilhelm, Ethel A

    2017-08-09

    The aim of the present study was to investigate the effects of SCH58261, a selective adenosine A2A receptor antagonist, on striatal toxicity induced by 3-nitropropionic acid (3-NP) in rats. The experimental protocol consisted of 10 administrations (once a day) of SCH58261 (0.01 or 0.05 mg/kg/day, intraperitoneal, i.p.). From 7th to 10th day, 3-NP (20 mg/kg/day, i.p.) was injected 1 h after SCH58261 administration. Twenty-four hours after the last 3-NP injection, the body weight gain, locomotor activity (open-field test), motor coordination (rotarod test), striatal succinate dehydrogenase (SDH) activity and parameters linked to striatal oxidative status were evaluated in rats. The marked body weight loss resulting from 3-NP injections in rats was partially protected by SCH 58261 at both doses. SCH 58261 at the highest dose was effective against impairments on motor coordination and locomotor activity induced by 3-NP. SCH 58261 was unable to restore the inhibition of SDH activity caused by 3-NP. In addition, the increase in striatal reactive species (RS) levels, depletion of reduced glutathione (GSH) content and stimulation of glutathione reductase (GR) activity provoked by 3-NP injections were alleviated by both doses of SCH 58261. The highest dose of SCH 58261 was also effective in attenuating the increase of protein carbonyl levels as well as the inhibition of glutathione peroxidase (GPx) activity in rats exposed to 3-NP. Our results revealed that reduction of oxidative stress in rat striatum by adenosine A2A receptor antagonism contributes for alleviating 3-NP-induced toxicity.

  9. 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.

  10. 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

  11. 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.

  12. Prenatal exposure to testosterone impairs oxidative damage repair efficiency in the domestic chicken (Gallus gallus).

    PubMed

    Treidel, L A; Whitley, B N; Benowitz-Fredericks, Z M; Haussmann, M F

    2013-10-23

    Elevated levels of maternal androgens in avian eggs affect numerous traits, including oxidative stress. However, current studies disagree as to whether prenatal androgen exposure enhances or ameliorates oxidative stress. Here, we tested how prenatal testosterone exposure affects oxidative stress in female domestic chickens (Gallus gallus) during the known oxidative challenge of an acute stressor. Prior to incubation, eggs were either injected with an oil vehicle or 5 ng testosterone. At either 17 or 18 days post-hatch, several oxidative stress markers were assessed from blood taken before and after a 20 min acute stressor, as well as following a 25 min recovery from the stressor. We found that, regardless of yolk treatment, during both stress and recovery all individuals were in a state of oxidative stress, with elevated levels of oxidative damage markers accompanied by a reduced total antioxidant capacity. In addition, testosterone-exposed individuals exhibited poorer DNA damage repair efficiencies in comparison with control individuals. Our work suggests that while yolk androgens do not alter oxidative stress directly, they may impair mechanisms of oxidative damage repair.

  13. 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.

  14. 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

  15. The effect of two-week L-carnitine supplementation on exercise -induced oxidative stress and muscle damage.

    PubMed

    Parandak, Khadijeh; Arazi, Hamid; Khoshkhahesh, Faegheh; Nakhostin-Roohi, Babak

    2014-06-01

    This study was conducted to assess the effect of Two-week L-carnitine supplementation on known markers of oxidative stress and muscle damage following acute bouts of exercise in active healthy young men. Twenty-one active healthy men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into two groups: L-carnitine (C group; n=10) and placebo group (P group; n=11). They arrived at the laboratory after overnight fasting. A baseline blood sample was taken. Afterwards, subjects consumed either L-carnitine (2 capsules containing totally 2000 mg L-carnitine) or placebo (2 capsules containing totally 2000 mg lactose) daily for 14 days. On the day of the test, participants attended the athletics arena after overnight fasting. Then, participants were asked to run 14 km on the track at their highest ability. Blood samples were taken immediately, 2, and 24 hours after exercise. Plasma total antioxidant capacity (TAC), malondialdehyde (MDA) as thiobarbituric acid-reactive substance (TBARS) as a marker of lipid peroxidation, creatine kinase (CK) and lactate dehydrogenase (LDH) as markers of muscle damage were measured. TAC increased significantly 14 days after supplementation and 24h after exercise in C group compared with P group (P<0.05). Serum MDA-TBARS, CK, and LDH were significantly lower 24h after exercise in C group compared with P group (P<0.05). These results suggest that two-week daily oral supplementation of L-carnitine has alleviating effects on lipid peroxidation and muscle damage markers following an acute bout of exercise in active healthy young men.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Supplementation of ascorbic acid and alpha-tocopherol prevents arsenic-induced protein oxidation and DNA damage induced by arsenic in rats.

    PubMed

    Kadirvel, R; Sundaram, K; Mani, S; Samuel, S; Elango, N; Panneerselvam, C

    2007-12-01

    Contamination of arsenic in drinking water is associated with several human diseases including cancer. It has been reported that oxidative stress plays a vital role in arsenic-induced biochemical and molecular alterations. The aim of the present study was to improve the understanding of arsenic-induced oxidative damage to proteins and to DNA and the role of antioxidants such as ascorbic acid and alpha-tocopherol in alleviating arsenic-induced damages in experimental rats. A significant increase in the levels of protein oxidation, DNA strand breaks, and DNA-protein cross-links was observed in blood, liver, and kidney of rats exposed to arsenic (100 ppm in drinking water) for 30 days. Co-administration of ascorbic acid and alpha-tocopherol to arsenic-exposed rats showed a substantial reduction in the levels of arsenic-induced oxidative products of protein and DNA. The results of this study support that free radical-mediated toxic manifestations of arsenic and also suggest that ascorbic acid and alpha-tocopherol supplementation can improve the arsenic-induced molecular alterations.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Unbalanced oxidant-induced DNA damage and repair in COPD: a link towards lung cancer.

    PubMed

    Caramori, Gaetano; Adcock, Ian M; Casolari, Paolo; Ito, Kazuhiro; Jazrawi, Elen; Tsaprouni, Loukia; Villetti, Gino; Civelli, Maurizio; Carnini, Chiara; Chung, Kian Fan; Barnes, Peter J; Papi, Alberto

    2011-06-01

    Chronic obstructive pulmonary disease (COPD) is characterised by oxidative stress and increased risk of lung carcinoma. Oxidative stress causes DNA damage which can be repaired by DNA-dependent protein kinase complex. To investigate DNA damage/repair balance and DNA-dependent protein kinase complex in COPD lung and in an animal model of smoking-induced lung damage and to evaluate the effects of oxidative stress on Ku expression and function in human bronchial epithelial cells. Protein expression was quantified using immunohistochemistry and/or western blotting. DNA damage/repair was measured using colorimetric assays. 8-OH-dG, a marker of oxidant-induced DNA damage, was statistically significantly increased in the peripheral lung of smokers (with and without COPD) compared with non-smokers, while the number of apurinic/apyrimidinic (AP) sites (DNA damage and repair) was increased in smokers compared with non-smokers (p = 0.0012) and patients with COPD (p < 0.0148). Nuclear expression of Ku86, but not of DNA-PKcs, phospho-DNA-PKcs, Ku70 or γ-H2AFX, was reduced in bronchiolar epithelial cells from patients with COPD compared with normal smokers and non-smokers (p < 0.039). Loss of Ku86 expression was also observed in a smoking mouse model (p < 0.012) and prevented by antioxidants. Oxidants reduced (p < 0.0112) Ku86 expression in human bronchial epithelial cells and Ku86 knock down modified AP sites in response to oxidative stress. Ineffective DNA repair rather than strand breakage per se accounts for the reduced AP sites observed in COPD and this is correlated with a selective decrease of the expression of Ku86 in the bronchiolar epithelium. DNA damage/repair imbalance may contribute to increased risk of lung carcinoma in COPD.

  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. MECHANISMS FOR COUNTERING OXIDATIVE STRESS AND DAMAGE IN RETINAL PIGMENT EPITHELIUM

    PubMed Central

    Plafker, Scott M.; O’Mealey, Gary B.; Szweda, Luke I.

    2013-01-01

    Clinical and experimental evidence supports that chronic oxidative stress is a primary contributing factor to numerous retinal degenerative diseases, such as age-related macular degeneration (AMD). Eyes obtained postmortem from AMD patients have extensive free radical damage to the proteins, lipids, DNA, and mitochondria of their retinal pigment epithelial (RPE) cells. In addition, several mouse models of chronic oxidative stress develop many of the pathological hallmarks of AMD. However, the extent to which oxidative stress is an etiologic component versus its involvement in disease progression remains a major unanswered question. Further, whether the primary target of oxidative stress and damage is photoreceptors or RPE cells, or both, is still unclear. In this review, we discuss the major functions of RPE cells with an emphasis on the oxidative challenges these cells encounter and the endogenous antioxidant mechanisms employed to neutralize the deleterious effects that such stresses can elicit if left unchecked. PMID:22878106

  14. Oxidative Stress in Ischemic Brain Damage: Mechanisms of Cell Death and Potential Molecular Targets for Neuroprotection

    PubMed Central

    Chen, Hai; Yoshioka, Hideyuki; Kim, Gab Seok; Jung, Joo Eun; Okami, Nobuya; Sakata, Hiroyuki; Maier, Carolina M.; Narasimhan, Purnima; Goeders, Christina E.

    2011-01-01

    Abstract Significant amounts of oxygen free radicals (oxidants) are generated during cerebral ischemia/reperfusion, and oxidative stress plays an important role in brain damage after stroke. In addition to oxidizing macromolecules, leading to cell injury, oxidants are also involved in cell death/survival signal pathways and cause mitochondrial dysfunction. Experimental data from laboratory animals that either overexpress (transgenic) or are deficient in (knock-out) antioxidant proteins, mainly superoxide dismutase, have provided strong evidence of the role of oxidative stress in ischemic brain damage. In addition to mitochondria, recent reports demonstrate that NADPH oxidase (NOX), an important pro-oxidant enzyme, is also involved in the generation of oxidants in the brain after stroke. Inhibition of NOX is neuroprotective against cerebral ischemia. We propose that superoxide dismutase and NOX activity in the brain is a major determinant for ischemic damage/repair and that these major anti- and pro-oxidant enzymes are potential endogenous molecular targets for stroke therapy. Antioxid. Redox Signal. 14, 1505–1517. PMID:20812869

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

    PubMed

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

    2017-04-01

    High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H2O2). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H2O2. These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

  16. CUX2 protein functions as an accessory factor in the repair of oxidative DNA damage.

    PubMed

    Pal, Ranjana; Ramdzan, Zubaidah M; Kaur, Simran; Duquette, Philippe M; Marcotte, Richard; Leduy, Lam; Davoudi, Sayeh; Lamarche-Vane, Nathalie; Iulianella, Angelo; Nepveu, Alain

    2015-09-11

    CUX1 and CUX2 proteins are characterized by the presence of three highly similar regions called Cut repeats 1, 2, and 3. Although CUX1 is ubiquitously expressed, CUX2 plays an important role in the specification of neuronal cells and continues to be expressed in postmitotic neurons. Cut repeats from the CUX1 protein were recently shown to stimulate 8-oxoguanine DNA glycosylase 1 (OGG1), an enzyme that removes oxidized purines from DNA and introduces a single strand break through its apurinic/apyrimidinic lyase activity to initiate base excision repair. Here, we investigated whether CUX2 plays a similar role in the repair of oxidative DNA damage. Cux2 knockdown in embryonic cortical neurons increased levels of oxidative DNA damage. In vitro, Cut repeats from CUX2 increased the binding of OGG1 to 7,8-dihydro-8-oxoguanine-containing DNA and stimulated both the glycosylase and apurinic/apyrimidinic lyase activities of OGG1. Genetic inactivation in mouse embryo fibroblasts or CUX2 knockdown in HCC38 cells delayed DNA repair and increased DNA damage. Conversely, ectopic expression of Cut repeats from CUX2 accelerated DNA repair and reduced levels of oxidative DNA damage. These results demonstrate that CUX2 functions as an accessory factor that stimulates the repair of oxidative DNA damage. Neurons produce a high level of reactive oxygen species because of their dependence on aerobic oxidation of glucose as their source of energy. Our results suggest that the persistent expression of CUX2 in postmitotic neurons contributes to the maintenance of genome integrity through its stimulation of oxidative DNA damage repair. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. 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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. 17β-Estradiol Alters Oxidative Stress Response Protein Expression and Oxidative Damage in the Uterus

    PubMed Central

    Yuan, Lisi; Dietrich, Alicia K.; Nardulli, Ann M.

    2014-01-01

    The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels.Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis. PMID:24103313

  19. 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.

  20. 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.

  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. 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.

  3. 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.

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

    PubMed

    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

    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. 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. 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