Oxidative stress induced by atrazine in rat erythrocytes: Mitigating effect of vitamin E

The present study investigates the propensity of atrazine to induce oxidative stress and its possible attenuation by vitamin E in rat erythrocytes, which is a convenient model to understand the oxidative damage induced by various xenobiotics. Experimental animals were administered atrazine (300?mg/kg body weight, daily) and/or vitamin E (100?mg/kg body weight, daily) orally for a period of 7, 14, and 21 days. Results indicated that the reduced glutathione (GSH) content of the erythrocytes of atrazine treated rats was significantly decreased as compared to the control group. Co-administration of vitamin E along with atrazine restored the GSH content of erythrocytes nearly to control levels. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione-s-transferase were found to be increased significantly in the erythrocytes accompanied by a decrease in the activity of the glucose-6-phosophate dehydrogenase, following atrazine exposure. On the other hand, when vitamin E was co-administered along with atrazine, activities of these enzymes were found to be restored significantly. In conclusion, results of the study demonstrated that atrazine induced oxidative stress in rat erythrocytes, in terms of increased activities of the various antioxidant enzymes, and decreased content of reduced glutathione. However, vitamin E administration ameliorated the effects of atrazine, suggesting that vitamin E is a potential antioxidant against atrazine-induced oxidative stress.     

Oxidative stress induced by lambda-cyhalothrin (LTC) in rat erythrocytes and brain: Attenuation by vitamin C

The objective of this study was to investigate the propensity of lambda-cyhalothrin (LTC) to induce oxidative stress in blood and brain of male Wistar rats and its possible attenuation by vitamin C. Rats were randomly divided into four groups: group I served as control rats. group II was treated daily with 200mgvit C/(kgbw) administered by intraperitoneal way. Rats of group III have received orally 668ppm LTC. Animals of group IV were treated with LTC and vitamin C. A decrease of some hematologic parameters (RBC, Hb, Ht: p<0.01) and a significant increase of MDA levels (p<0.05) in erythrocytes and brain were observed in LTC group compared to controls. Antioxidant enzyme activities in both tissues were modified in LTC group compared to controls. Administration of vitamin C ameliorated these parameters. Our results indicated the potential effects of LTC to induce oxidative damage in tissues and the ability of vitamin C to attenuate LTC-induced oxidative damage.     

丙烯腈对大鼠脑皮层氧化应激效应的研究

目的　评价长期低浓度接触AN对大鼠脑组织的氧化性应激效应 ,探讨AN神经毒性机制。方法　SD雄性大鼠 3 0只 ,随机分成 3组 :对照组、低剂量组和高剂量组 ,通过饮水分别给予 0、5 0和 2 0 0mg L的AN溶液。染毒时间为 12周。染毒结束后从每组随机选取 7只大鼠 ,取双侧大脑皮层测定氧化性应激指标。结果　染毒组的MDA水平(nmol mg蛋白 )明显高与对照组 (16 60± 6 49) ,且高剂量组 (15 7 7± 85 40 )明显高于低剂量组 (98 5 3± 5 0 3 5 ) ,其剂量 效应关系有显著性 ;3组之间的GSH Px活力差异未见显著性 ;虽然低剂量组的SOD活力和对照组的差异未见显著性 ,但高剂量组明显高于对照组和低剂量组。高剂量组GSH明显低于对照组和低剂量组 ,但低剂量组和对照组的差异无显著性。结论　诱导氧化性应激可能是AN神经毒性的重要作用机制。     

Oxidative stress and mitochondrial dysfunction in glaucoma

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Highlights► Oxidative stress is thought to contribute to the pathogenesis of glaucoma. ► Mitochondria are a central source and target of oxidative stress. ► Signs of oxidative stress and damage are present in glaucomatous tissue. ► Reactive oxygen species can cause retinal ganglion cell death directly or indirectly. ► Mitochondrial antioxidants may improve disease outcomes in glaucoma.     

Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat erythrocytes

Isoproterenol, upon oxidation, produces quinones which react with oxygen to produce superoxide anions (O2.-) and H2O2. In the present study, isoproterenol was administered to rats in two doses so as to evaluate its beta adrenergic and toxicological action in terms of lipid peroxidation (LPO) and antioxidant enzymes in erythrocytes. Isoproterenol (30 mg/100 g body wt.) was administered to rats and the animals were followed up to 7 days after administration. Some of these animals were treated with a second dose of isoproterenol 24 h after the first dose and the animals were followed up to 12 h. The result showed increased lipid peroxidation (LPO) and superoxide dismutase (SOD) activity in erythrocytes in response to isoproterenol. Catalase (CAT) activity in erythrocytes decreased with isoproterenol between day 2-7 as compared to control. The second injection of isoproterenol showed increased CAT activity in erythrocytes which decreased at 12 h as compared to control. The erythrocyte GSH content and glutathione-S-transferase (GST) activity decreased with isoproterenol treatment as compared to control. However, erythrocyte GSH content as well as GST activity both recovered towards control with time. Elevated serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and glutamate oxaloacetate transaminase (GOT) activity was observed after isoproterenol treatment. The results show increased LPO and altered antioxidant system in erythrocytes in response to isoproterenol induced oxidative stress.     

Modulation of N-nitrosodiethylamine (NDEA) induced oxidative stress by vitamin E in rat erythrocytes

Nitrosamines, such as N-nitrosodiethylamine (NDEA), induced oxidative stress due to the generation of reactive oxygen species, which are capable of initiating peroxidative damage to the cell. The present study was designed to establish whether pre-treatment with vitamin E (40 mg/kg body wt, intraperitoneally (ip), twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress caused by NDEA. A single necrogenic dose of NDEA (200 mg/kg body wt) was administered intraperitoneally (ip) to the rats with or without vitamin E pre-treatment and the animals were sacrificed on Day 7, 14 or 21 after NDEA administration. Lipid peroxidation (LPO) and the activities of antioxidant enzymes were determined in erythrocytes as indices of oxidative damage. The result showed elevated levels of LPO in erythrocytes with NDEA treatment, however, vitamin E pre-treated rats administered NDEA showed decreased LPO (Day 14 and 21). Superoxide dismutase (SOD) enzyme activity and the glutathione (GSH) content increased with NDEA treatment and remained high in vitamin E pre-treated group. Catalase (CAT), glutathione reductase (GSH-R) and glutathione-S-transferase (GST) enzyme activities declined with NDEA treatment; however, vitamin E pre-treated rats administered NDEA, showed elevation in the enzyme activities. Glutathione peroxidase (GSH-Px) activity increased in erythrocytes in vitamin E pre-treated rats administered NDEA, while Se-GSH-Px activity was not affected significantly. This study demonstrates that the pre-treatment with vitamin E prior to the administration of NDEA was effective in counteracting and modulating oxidative stress in rat erythrocytes in a time-dependent manner.     

帕博利珠单抗致甲状腺功能障碍文献分析

目的 探索帕博利珠单抗致甲状腺功能障碍发生的规律和临床特点,为临床安全用药提供参考。方法 检索知网、维普、万方、PubMed、Web of Science数据库,收集关于帕博利珠单抗致免疫性皮肤病的文献数据并进行统计分析。结果 纳入16篇文献,共16例甲状腺功能障碍病例,年龄为30～77岁;甲状腺功能障碍发生时间最早为给药后14 d,最晚为给药后240 d;常规给予左甲状腺素治疗甲状腺功能减退及给予甲硫咪唑治疗甲状腺功能亢进,经过治疗后多数患者甲状腺功能障碍好转。结论 在使用帕博利珠单抗时要注意监测甲状腺功能障碍不良反应,一旦发生应及时进行相应治疗。     

Oxidative stress and apoptosis in cardiomyocyte induced by high-dose alcohol

Binge drinking of alcohol causes cardiac dysfunction in some people. The mechanism remains unclear. This study was designed to investigate high doses of alcohol-induced oxidative stress and apoptosis in cardiomyocytes and protective effects of antioxidants. Cardiomyocytes isolated from 1- to 2-day-old Sprague-Dawley rats were treated with ethanol at doses of 0 mM, 50 mM, 100 mM, and 200 mM for 24 hours. Vitamin E (1 mM) and vitamin C (0.2 mM) were added to medium 1 hour before addition of ethanol. Results showed typical apoptosis: chromatin condensation, membrane blebbing, shrinkage, and cytoplasm condensation. Apoptosis is concentration-dependent in the range of 0 to 100 mM ethanol (apoptosis rates were respectively 0.68%, 2.03%, and 9.66% at ethanol concentration of 0 mM, 50 mM, and 100 mM). Necrotic cells became greatly increased in the 200 mM ethanol-treated group. Intracellular production of reactive oxygen intermediates increased as mitochondrial membrane potential decreased after ethanol treatment. Cytochrome c was found to be greater in the cytosol of the ethanol-treated groups. Activity of caspase-3 was higher in ethanol-treated groups (P < 0.05). Both vitamin E and vitamin C inhibited oxidative stress and myocyte apoptosis in ethanol-treated groups (P < 0.05). In conclusion, our data indicated that acute high-dose ethanol treatment primarily induces cardiomyocyte apoptosis at concentration up to 100 mM while necrosis is predominate at 200 mM. The underlying mechanism appears to involve mitochondrial damage via an increase in oxidative stress and releasing cytochrome c, which activates caspases that initiate chromatin fragmentation and apoptosis. Antioxidants, to a large extent, inhibit oxidative stress and apoptosis induced by ethanol.     

Oxidative stress and mitochondrial dysfunction in type 2 diabetes

Diabetes is a chronic disease and as a consequence of the overproduction of reactive oxygen species (ROS), is related with oxidative stress. There are different sources of ROS, of which mitochondria is the main one. Oxidative stress seems to play an important role in mitochondria- mediated disease processes, though the exact molecular mechanisms responsible remain elusive. There are evidences which supports the idea that impaired mitochondrial function is a cause of the insulin insensitivity in different type of cells that arised as a result of an insufficient supply of energy or defects in the insulin signaling pathway. ROS are generally necessary for the proper functioning of the cell, but excessive ROS production can be harmful, which makes antioxidant defenses essential. Moreover, some substances with antioxidant properties, such as vitamin C or vitamin E, erradicate the oxidative stress associated with diabetes. The results of clinical trials employing anti-oxidative stress reagents in patients with diabetes are contradictory, which may be a result of inadequate study design or selected targets. This review considers the process of diabetes from a mitochondrial perspective, and describes the role of autophagy in the development of diabetes. Furthermore, we discuss the possible beneficial effects of selectively targeting antioxidants to mitochondria as a strategy for modulating mitochondrial function in diabetes.     

木犀草素减轻氧化应激引起的血管内皮损伤

目的：探讨木犀草素对叔丁基过氧化氢致血管内皮损伤的保护作用及相关机制。方法：首先通过制备大鼠胸主动脉环,观察木犀草素对叔丁基过氧化氢所致血管张力变化的影响;再采用叔丁基过氧化氢诱导血管内皮细胞氧化损伤模型,观察木犀草素对其细胞形态学变化及细胞活力的影响,并用RT-PCR检测eNOS和COX-1 mRNA的含量变化。结果：木犀草素能够浓度依赖性地对抗叔丁基过氧化氢导致的血管舒张功能损伤及细胞损伤作用,且浓度依赖性地减弱叔丁基过氧化氢对内皮细胞eNOS mRNA表达抑制的影响。结论：木犀草素是一种有效的舒血管物质,它可以起到抗氧化的作用,减轻氧化应激反应,并可能通过维持eNOS活性等血管内皮途径舒张血管。     

Oral administration of geranylgeranylacetone blunts the endothelial dysfunction induced by ischemia and reperfusion in the rat heart

It has been shown that geranylgeranylacetone (GGA) protects heart against ischemia/reperfusion injury via enhanced heat shock protein 72 (HSP72) expression in rats. In the present study, we investigated the protective effect of GGA on ischemia/reperfusion-induced endothelial dysfunction. Rats were given oral GGA (GGA group) or vehicle (CON group), and 24 hours later their hearts were removed and placed in the Langendorff apparatus for 30-minute low-flow ischemia followed by 30-minute reperfusion. GGA improved the postischemic functional recovery (P < 0.01), which was abolished by N-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor). NO production during both ischemia and reperfusion were increased in the GGA group, and the acetylcholine (ACh)-induced (endothelium-dependent) vasodilation, measured as the percentage decrease in coronary perfusion pressure after ischemia/reperfusion (14.9 +/- 1.3%), was preserved as compared with that in the CON group (7.9 +/- 1.4%). LY294002, a phosphatidylinositol 3 (PI3) kinase inhibitor, abolished the protective effects of GGA on endothelial-dependent coronary vasodilation and NO production, whereas Y27632 (Rho kinase inhibitor) increased endothelium-dependent coronary vasodilation and NO production in CON group toward the level seen in GGA group. The amount of adrenomedullin in the coronary effluent at basal condition was lower in the GGA group than in the CON group (P < 0.05), and during both ischemia and reperfusion there was no difference in the amount of adrenomedullin between the GGA and CON groups. In addition, no difference was observed in the amount of endothelin-1 between the GGA and CON groups. These results indicate that GGA attenuates the ischemia/reperfusion-induced coronary endothelial dysfunction, which may contribute to its cardioprotective effect. The PI3 kinase and/or Rho kinase pathways appear to be involved in this process, whereas adrenomedullin and endothelin-1 are not necessary for the GGA-induced cardioprotection.     

Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain.

Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neurodegenerative disorders. We have previously demonstrated that chronic stress induced an increase in nitric oxide (NO) production via an expression of inducible NO synthase (iNOS) in brain. Since it has been demonstrated that NO regulates mitochondrial function, we sought to study the susceptibility of the mitochondrial respiratory chain complexes to chronic restrain stress exposure in brain cortex. In adult male rats, stress (immobilization for six hours during 21 days) inhibits the activities of the first complexes of the mitochondrial respiratory chain (inhibition of 69% in complex I-III and of 67% in complex II-III), without affecting complex IV activity, ATP production and oxygen consumption. The mitochondrial marker citrate synthase is not significantly affected by stress after 21 days, indicating that at this time the mitochondrial structure is still intact. Moreover, the administration of the preferred inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (400 mg/kg i.p. daily from days 7 to 21 of stress) protects against the inhibition of the activity of complexes of the mitochondrial respiratory chain as well as prevents NO(x)(-) accumulation, lipid peroxidation and glutathione depletion induced by stress. These results suggest that a sustained overproduction of NO via iNOS is responsible, at least in part, of the inhibition of mitochondrial respiratory chain caused by stress and that this pathway also accounts for the oxidative stress found in this situation.     

Oxidative stress in Cyprinus carpio induced by hospital wastewater in Mexico

Ecotoxicology - The very wide range of activities performed in hospitals (care, diagnosis, hygiene, maintenance, research) require the use of a large variety of potentially ecotoxic substances such...     

香烟烟雾溶液作用下大鼠淋巴细胞的氧化应激反应

目的　以细胞内活性氧自由基 (ROS)水平、DNA损伤、脂质过氧化物 (LPO)水平以及超氧化物歧化酶 (SOD)活力为指标 ,研究细胞在香烟烟雾溶液作用下产生的氧化应激反应。方法　以PBS作吸收液 ,用大包氏管收集香烟主流烟雾 ,将香烟烟雾溶液 (CSS)分别以 0、1× 10 - 3、2× 10 - 3、4× 10 - 3、8× 10 - 3、12× 10 - 3、16× 10 - 3支 ml的浓度作用于大鼠淋巴细胞。用 2′ ,7′ 二乙酰二氯荧光素 (DCFH DA)测定细胞内ROS水平 ,用彗星试验检测细胞DNA损伤 ,同时检测细胞内SOD活力和LPO水平。结果　 2× 10 - 3支 ml以上剂量组二氯荧光素 (DCF)荧光强度、彗星尾长以及LPO水平均显著高于对照组 ,且随剂量增加而增加。 16× 10 - 3支 ml组SOD活力显著低于对照组。与对照组相比 ,1× 10 - 3支 ml组LPO水平显著降低、SOD活力则显著增高。结论　CSS达到一定剂量时使细胞内ROS水平增高 ,引起细胞DNA损伤和脂质过氧化 ,高剂量时SOD活力降低 ,而低剂量时能够诱导SOD活力     

Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria

Isoniazid (INH or isonicotinic hydrazide) is used for the treatment and prophylaxis of tuberculosis. Liver and brain are two important target organs in INH toxicity. However, the exact mechanisms behind the INH hepatotoxicity or neurotoxicity have not yet been completely understood. Considering the mitochondria as one of the possible molecular targets for INH toxicity, the aim of this study was to evaluate the mechanisms of INH mitochondrial toxicity on isolated mitochondria. Mitochondria were isolated by differential ultracentrifugation from male Sprague–Dawley rats and incubated with different concentrations of INH (25–2000?μM) for the investigation of mitochondrial parameters. The results indicated that INH could interact with mitochondrial respiratory chain and inhibit its activity. Our results showed an elevation in mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation and mitochondrial membrane potential collapse after exposure of isolated liver mitochondria in INH. However, different results were obtained in brain mitochondria. Noteworthy, significant glutathione oxidation, adenosine triphosphate (ATP) depletion and lipid peroxidation were observed in higher concentration of INH, as compared to liver mitochondria. In conclusion, our results suggest that INH may initiate its toxicity in liver mitochondria through interaction with electron transfer chain, lipid peroxidation, mitochondrial membrane potential decline and cytochrome c expulsion which ultimately lead to cell death signaling.     

DNA fragmentation and DNA repair synthesis induced in rat and human thyroid cells by four rat thyroid carcinogens

Four chemicals that are known to induce in rats thyroid follicular-cell adenomas and carcinomas were assayed for their ability to induce DNA damage and DNA repair synthesis in primary cultures of human thyroid cells. Significant dose-dependent increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measures by the Comet assay, were obtained after a 20-h exposure to the following subtoxic concentrations of the four test compounds: 2,4-diaminoanisole (DAA) from 0.10 to 1.0 mM, 4,4'-methylene-bis(N,N-dimethyl)benzenamine (MDB) from 0.32 to 1.8 mM, propylthiouracil (PTU) from 1.8 to 5.6 mM, and 4,4'-thiodianiline (THA) from 0.032 to 0.18 mM. Under the same experimental conditions, DNA repair synthesis, as evaluated by quantitative autoradiography, was present in thyreocytes exposed to DAA but absent after treatment with MDB, PTU, and THA. Consistent with their thyroid-specific carcinogenic activity, all the four chemicals, administered p.o. in rats in a single dose corresponding to 1/2 LD50, induced a statistically significant degree of DNA fragmentation in the thyroid, whereas any substantial evidence of DNA lesions was absent in liver, kidney, and lung, which, with the exception of liver tumors caused by THA, are not targets of the carcinogenic activity of the four test compounds. These findings indicate that the DNA damage observed in thyroid cells was consistent with the carcinogenicity of the four test compounds, and suggest that DAA, MDB, PTU, and THA might be carcinogenic to thyroid in humans.     

Role of the hepatic xanthine oxidase in thyroid dysfunction: effect of thyroid hormones in oxidative stress in rat liver

The effect of thyroid hormones on the hepatic xanthine oxidase activity was studied in rats after the intraperitoneal injections of comthyroid (triiodotyronine: thyroxine=1 :4) at 0.3 mg/kg for 3 consecutive days. The aim of this study was to understand the precise mechanism of hyperthyroidism induced by oxidative stress. The concentration of lipid peroxides determined indirectly by the measurement of thiobarbituric acid reactants was increased in comthyroid treated rats. The hepatic glutathione content was decreased in comthyroid injected rat compared to the euthyroid state. It was also observed that the increment of xanthine oxidase activity has a profound role in oxygen radicals generation system in comthyroid treated rat. These findings suggest that the enhanced xanthine oxidase activity and depleting glutathione content in comthyroid treated rats result in pathophysiological oxidative stress including an increment of hepatic lipid peroxidation.     

Oxidative stress during myocardial ischaemia and heart failure

Oxidative stress is a condition in which oxidant metabolites exert their toxic effect because of an increased production or an altered cellular mechanism of protection. The heart needs oxygen avidly and, although it has powerful defence mechanisms, it is susceptible to oxidative stress, which occurs, for instance, during post-ischaemic reperfusion. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals, mainly a reduction in the activity of mitochondrial superoxide dismutase and a depauperation of tissue content of reduced glutathione. At the same time, production of oxygen free radicals increases in the mitochondria and leukocytes and toxic oxygen metabolite production is exacerbated by re-admission of oxygen during reperfusion. Oxidative stress, in turn, causes oxidation of thiol groups and lipid peroxidation leading first to reversible damage, and eventually to necrosis. In man, there is evidence of oxidative stress (determined by release of oxidised glutathione in the coronary sinus) during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. Data on oxidative stress in the failing heart are scant. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Relevant to heart failure is the finding that tumour necrosis factor, which is found increased in failing patients, induces a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but occurs also at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. It is therefore, possible that the immunological response to heart failure results in endothelial and myocyte dysfunction through oxidative stress mediated apoptosis. Clarification of these mechanisms may lead to novel therapeutic strategies.     

High fat diet aggravates arsenic induced oxidative stress in rat heart and liver

Arsenic is a well known global groundwater contaminant. Exposure of human body to arsenic causes various hazardous effects via oxidative stress. Nutrition is an important susceptible factor which can affect arsenic toxicity by several plausible mechanisms. Development of modern civilization led to alteration in the lifestyle as well as food habits of the people both in urban and rural areas which led to increased use of junk food containing high level of fat. The present study was aimed at investigating the effect of high fat diet on heart and liver tissues of rats when they were co-treated with arsenic. This study was established by elucidating heart weight to body weight ratio as well as analysis of the various functional markers, oxidative stress biomarkers and also the activity of the antioxidant enzymes. Histological analysis confirmed the biochemical investigations. From this study it can be concluded that high fat diet increased arsenic induced oxidative stress.     

氯丁二烯吸入染毒致大鼠急性肝损害的氧化应激机理

大鼠吸入浓度为6.08 mg·L~(-1)氯丁二烯4 h后。2,12和24 h处死.染毒后2 h时血清SDH即明显升高,继而ALT升高,前者增高的幅度大于后者,肝匀浆GSH明显下降,然后升高,脂质过氧化产物MDA形成增多,肝线粒体膜脂流动性下降,与线粒体膜结合的ANS荧光增强,表明氯丁二烯所致急性肝损害可能与氧化应激机理有关。