Role of oxidative stress and nitric oxide in the protective effects of α-lipoic acid and aminoguanidine against isoniazid–rifampicin-induced hepatotoxicity in rats

Despite the great efficacy of isoniazid (INH) and rifampicin (RIF) combination, in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of α-lipoic acid and aminoguanidine; against combination-induced hepatotoxicity was investigated in the present study. Administration of INH–RIF combination (50 mg/kg each for 14 days) resulted in an elevation of serum hepatic marker enzymes and a significant increase in lipid profile parameters. Combinations treatment increased lipid peroxidation products, decreased glutathione content, superoxide dismutase, catalase and myeloperoxidase activities. Furthermore, liver total nitrite level was significantly increased in INH–RIF treated rats. Co-administration of either α-lipoic acid or aminoguanidine significantly ameliorate combination-induced alterations in hepatic marker enzymes. These effects were directly linked to a greater decrease in the combination-induced elevation in lipid peroxidation products and total nitrite levels. Furthermore, co-administration of α-lipoic acid and aminoguanidine restore superoxide dismutase, catalase and myeloperoxidase activities and maintained the imbalance in the glutathione level. Additionally, such beneficial effect of α-lipoic acid was linked to a marked lipid-lowering effect. Histopathological examination revealed preservation of liver integrity of the protected groups compared to combination-treated rats alone.     

Changes in tissue oxidative stress,brain biogenic amines and acetylcholinesterase following co-exposure to lead,arsenic and mercury in rats

The present study investigated the toxic effects of individual, combined (binary and ternary) exposure to lead, arsenic and mercury on, (i) oxidative stress (ii) alterations in brain biogenic amines and (iii) tissue metals concentration. Rats were exposed to lead, arsenic and mercury either individually (30 ppm in drinking water), various binary (15 ppm each) or ternary combination (10 ppm each) for a period of 6 months. Lead + arsenic and lead + arsenic + mercury co-exposure led to a significant increase in the blood oxidative stress. Mercury + arsenic and lead + arsenic + mercury co-exposure produced a more pronounced hepatotoxicity while, lead + arsenic and lead + arsenic + mercury produced a significant increase in hepatic oxidative stress. Kidney oxidative stress and changes in brain biogenic amines were more prominent in animals exposed to three metals. Accumulation of three metals did not exhibit the pattern as in the case of oxidative stress. Exposure to two toxic metals also showed less accumulation of toxic metals suggesting possible antagonism. The present study thus provides some interesting observations on the interaction between lead, arsenic and mercury. Co-exposure to lead + arsenic + mercury led to a more pronounced increase in oxidative stress in liver and kidneys compared to other exposed groups.     

Lipid homeostasis and oxidative stress in the liver of male rats exposed to perfluorododecanoic acid

Perfluorododecanoic acid (PFDoA), a perfluorinated carboxylic acid (PFCA) with twelve carbon atoms, has broad industrial applications and is widely distributed in both wildlife and the environment. Unlike other PFCAs with short carbon chain, however, limited studies have been performed to date on the toxic effects of PFDoA on animals. To determine the hepatotoxicity of PFDoA, male rats were orally dosed by gavage for 14 days with 0, 1, 5, or 10 mg PFDoA/kg/day. Absolute liver weights were diminished, but the relative liver weight was significantly increased in the 5 and 10 mg PFDoA/kg/day groups. Meanwhile, serum triglyceride (TG) concentrations were decreased significantly in rats dosed with 1 and 5 mg PFDoA/kg/day, while the liver lipid accumulation was observed in ultrastructure. The expression of peroxisome proliferator-activated receptor (PPAR)-alpha and its target genes, and to a lesser extent PPARgamma, was induced by PFDoA. No significant changes in the expression of liver X receptor alpha (LXRalpha) or its target genes CYP7A1 and acetyl-CoA carboxylase 1 (ACC1) were noted, although the mRNA levels of several genes involved in lipogenesis and lipid transport were changed significantly in the certain of the experimental groups. In addition, superoxide dismutase (SOD) and catalase (CAT) activities were activated significantly in the 1 mg PFDoA/kg/day group and inhibited significantly with a concomitant increase of lipid peroxidation (LPO) levels in the 5 and 10 mg PFDoA/kg/day groups. Our results demonstrate that PFDoA exerts notable hepatotoxicity in male rats and that PPAR and its target genes, SOD and CAT activity, and LPO levels exhibited sensitivity to the toxicity of PFDoA.     

褪黑素对烫伤大鼠脑组织抗氧化能力与星形胶质细胞的影响

目的 观察褪黑素(melatonin,MT)对烫伤大鼠脑组织GSH、SOD与MDA含量与星形胶质细胞的影响,以探讨烫伤后MT的神经保护机制.方法 随机将30只SD大鼠,分为正常对照组、烫伤组和MT治疗组;MT治疗组在烫伤后10 min,3 h分别给予MT (10 mg/kg)腹腔注射治疗,对照组与烫伤组给予等量体积的生理盐水.MT治疗结束后1 h取脑行GSH、SOD与MDA含量检测,然后取额叶皮质行GFAP免疫组化染色,光镜下观察星形胶质细胞的形态变化并进行计量分析.结果 与正常对照组相比,烫伤组大鼠脑组织GSH含量下降,而SOD与MDA含量增加,GFAP阳性神经元增多(P<0.05).与烫伤组相比,MT治疗组大鼠脑组织GSH含量增加,SOD与MDA含量下降,GFAP阳性神经元减少 (P<0.05).结论 烫伤后早期应用MT治疗,可以改善机体的氧化应激水平和神经系统的继发性损伤.     

Combination of chlorogenic acid and salvianolic acid B protects against polychlorinated biphenyls-induced oxidative stress through Nrf2

Caffeic acid derivatives (CADs) are well-known phytochemicals with multiple physiological and pharmacological activities. This study aimed to investigate the combined protective effects of CADs on PCB126-induced liver damages and oxidative stress in mice. Here, we used chemiluminescence and chose chlorogenic acid (CGA), salvianolic acid B (Sal B) as the best antioxidants. Then, mice were intragastrically administered with 60 mg/kg/d CGA, Sal B, and CGA plus Sal B (1:1) for 3 weeks before exposing to 0.05 mg/kg/d PCB126 for 2 weeks. We found that pretreatment with CGA, Sal B, and CGA plus Sal B effectively attenuated liver injury and cytotoxicity caused by PCB126, but improved the expressions of superoxide dismutase (SOD), glutathione reduced (GSH), heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf2), CGA plus Sal B especially, was found to have the best effects that indicated a synergetic protective effect. Taken together, as the Nrf2 regulates the cyto-protective response by up-regulating the expression of antioxidant genes, we suggested that CGA plus Sal B had a combined protection on PCB126-induced tissue damages and that the Nrf2 signaling might be involved.     

Reversal of propoxur-induced impairment of step-down passive avoidance, transfer latency and oxidative stress by piracetam and ascorbic acid in rats

Propoxur, a carbamate pesticide has been shown to adversely affect memory and induce oxidative stress. The present study was designed to correlate the effect of propoxur, piracetam (a nootropic drug) and ascorbic acid (an antioxidant) on oxidative stress and cognitive function. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and non-protein thiol (NP-SH) levels. A significant reduction in SDL and prolongation of TL was found for the propoxur-treated group at weeks 6 and 7 as compared with control (p < 0.001). One week treatment by piracetam (400 mg/kg/d, i.p.) or ascorbic acid (120 mg/kg/d, i.p.) antagonized the effect of propoxur on SDL as well as TL. Both piracetam and ascorbic acid attenuated the propoxur-induced increase in brain MDA levels and decrease in brain NP-SH levels. Results of the present study show that ascorbic acid and piracetam have the potential to reverse cognitive dysfunction and oxidative stress induced by propoxur in the brain.     

Metallothionein attenuates carmustine-induced oxidative stress and protects against pulmonary fibrosis in rats

The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) against carmustine (BCNU)-induced lung toxicity in rats. A total of 60 rats were randomly divided into four groups (15/group): control group in which the animals received 0.5 ml physiologic saline containing 10% ethanol (IP) weekly, MT-administered group in which rats received MT (30 μmol/kg, IP) weekly, BCNU-administered group in which rats received BCNU (5 mg/kg, IP) weekly and MT + BCNU group in which rats received weekly doses of BCNU (5 mg/kg, IP) followed 24 h later by MT (30 μmol/kg, IP). At the end of the experiment (after 6 weeks), lung histological changes, collagen staining, the activity of glutathione reductase (GR) and contents of reduced glutathione (GSH) and hydroxyproline (Hpr) in the lung as well as serum level of tumor necrosis factor-alpha (TNF-α) were evaluated. The obtained data revealed that BCNU induced pathological changes and markedly increased lung collagen and level of Hpr but decreased GSH content and GR activity and increased serum TNF-α compared to both control and MT-administered rats. Administration of MT + BCNU markedly improved histological features and decreased staining of collagen along with increased GR activity, GSH content but decreased level of Hpr in lung tissue as well as decreased serum level of TNF-α compared with BCNU-treated rats. Based on our results, it is possible to postulate that exogenous MT can act against BCNU-induced lung toxicity by a mechanism related, at least in part, to its ability to decrease oxidative stress and fibrosis.     

单宁酸对糖尿病模型大鼠肾脏氧化应激水平及炎性因子表达的抑制作用

目的 观察单宁酸对糖尿病模型大鼠抗氧化能力的影响及对机体微炎症状态的改善作用.方法 选择6周龄健康雄性Wistar大鼠68只,随机选取其中8只作为正常对照组,其余60只给予高糖高脂饲料喂养4周后以链脲佐菌素（STZ）按52 mg/kg单次腹腔注射制造糖尿病大鼠模型,造模成功的大鼠进一步随机分为模型组、氨基胍组、单宁酸低剂量组、单宁酸高剂量组,各15只.氨基胍组及单宁酸低、高剂量组分别腹腔注射氨基胍40 mg/（kg·d）及单宁酸[20、30 mg/（kg·d）],正常对照组和模型组给予0.9％氯化钠注射液[30 mg/（kg·d）],10周后处死大鼠取材.化学比色法检测各组大鼠血清及肾皮质丙二醛含量及谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性;酶联免疫吸附测定法检测肾组织匀浆8-羟基脱氧鸟苷（8-OHdG）含量、血清C反应蛋白（CRP）水平;免疫组织化学检测肾组织细胞间黏附分子1（ICAM-1）、单核细胞趋化蛋白1（MCP-1）的蛋白表达,逆转录-聚合酶链反应检测肾组织ICAM-1、MCP-1 mRNA表达.结果 单宁酸低、高剂量组大鼠血清丙二醛含量明显低于模型组[（23.5±8.5）、（19.8±5.3） μmol/L比（35.5±14.6） μmol/L]（P＜0.05或P＜0.01）,GSH-Px、总SOD及CAT活性明显高于模型组[GSH-Px：（295 ±58）、（322±52） U/L比（232 ±72） U/L,总SOD：（75±13）、（86±15） U/ml比（49±13） U/ml,CAT：（6.9±2.2）、（7.2±2.9） U/ml比（3.7±1.4） U/ml]（P＜0.05或P＜0.01）;单宁酸低、高剂量组大鼠肾组织匀浆丙二醛含量明显低于模型组[（344±120）、（269±52） μmol/L比（464±62） μmol/L]（P＜0.05或P＜0.01）;单宁酸高剂量组GSH-Px活性明显高于模型组[（32 ±8）U/L比（17±4） U/L]（P＜0.01）;单宁酸低剂量组总SOD活性明显高于模型组[（23±4）U/ml比（17±4） U/ml] （P＜0.05）;单宁酸高剂量组大鼠肾组织8-O     

Concomitant exposure to arsenic and organophosphates on tissue oxidative stress in rats

Increased use of organophosphates (OPs) and ever increasing arsenic levels in drinking water and their co-existence in the environment could be potentially hazardous. The present study examines the effects of dichlorvos (DDVP) or monocrotophos (MCP) and sodium meta arsenite, individually or in combination for 16 weeks on variables indicative of hematological and tissue oxidative injury in rats. Co-exposure to DDVP, MCP or arsenic produced significant inhibition of brain and serum AChE levels suggesting synergism. Significant increase in hepatic reactive oxygen species and brain thiobarbituric acid reactive substances was observed in arsenic and OPs exposed animals. Co-exposure to arsenic and OPs exhibited synergism in case of ROS while antagonism was noted in case of TBARS. Serum transaminases increased significantly on exposure to OPs and arsenic suggesting liver injury which was less pronounced in case of co-exposure to DDVP and arsenic. WBC counts too showed less pronounced increase on co-exposure to arsenic with OPs compared to all other exposure. Blood arsenic level decreased on co-exposure to arsenic with OPs. The present study points to some interesting observations regarding interaction between arsenic and organophosphates. While, exposure to arsenic, DDVP and MCP lead to significant oxidative stress, their co-exposure not necessarily produce synergistic effects.     

Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides

Oxidative stress by increased production of reactive oxygen species has been implicated in the toxicity of many pesticides. Therefore, the aim of the present study was to investigate the effect of a broad spectrum insecticide, composed of a mixture of organophosphate plus pyrethroids (fenitrothion 25%, lambda cyhalothrin 2.5% and piperonyl butoxide 6%), on antioxidant status and oxidative stress biomarkers in rat brain. Different insecticide concentrations (0, 0.1, 1, 10, 100 and 1000 mM) were incubated with brain homogenate at 37 °C for time intervals (0, 30, 60, 120, 180 and 240 min). Exposure to insecticide mixture resulted in a significant increase (p < 0.05) in thiobarbituric acid reactive substances (TBARS), which might be associated with decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and acetylcholinesterase activities and beside protein content in rat brain. However, a significant induction of lactate dehydrogenase (LDH) activities was observed. The response was concentration and time dependent. Results showed that the used insecticides had the propensity to cause significant oxidative damage in rat brain, which is associated with marked perturbations in antioxidant defense system in addition to antioxidant enzymes can be used as potential biomarkers of toxicity associated with pesticides exposure.     

Exposure to diphenyl ditelluride,via maternal milk,causes oxidative stress in cerebral cortex,hippocampus and striatum of young rats

The present study evaluated the effect of diphenyl ditelluride [(PhTe)₂] exposure to mothers on the cerebral oxidative status of their offspring. The dams received (PhTe)₂ or canola oil via subcutaneous injection once daily during the first 14 days of lactational period. At post natal day 28, biochemical parameters of oxidative stress were evaluated in cerebral structures—cortex, hippocampus and striatum—of young rats. Exposure to (PhTe)₂ increased lipid peroxidation levels and inhibited δ-ALA-D, catalase and SOD activities in hippocampus and striatum of young rats. (PhTe)₂ induced changes in the levels of non-enzymatic antioxidant defenses in cortex and striatum of young rats. The exposure to (PhTe)₂, via maternal milk, caused oxidative stress in cerebral structures of young rats. Thus, the possible role of disrupted prooxidant/antioxidant balance in (PhTe)₂ toxicity was demonstrated. These results highlighted a possible molecular mechanism involved in toxicity caused by (PhTe)₂.     

氧化应激在氟中毒脑损伤中的意义

氟是机体必需的微量元素,如果体内氟蓄积增多,可以引起氟中毒。氟中毒是一种全身性疾病,氟可以在软组织器官蓄积引起不同程度的损害,脑是氟中毒的重要靶器官之一,吸收入体内的氟可以透过血脑屏障在脑组织中蓄积。氧化损伤主要是机体在遭受有害刺激时,活性氧自由基产生过多,氧化程度超出氧化物的清除,氧化系统和抗氧化系统之间严重失衡,从而造成包括蛋白质、脂质、DNA 和RNA在内的多种底物发生氧化应激,影响细胞的正常功能。在氟中毒发病机制的研究中,自由基与氧化应激是近年来的热点之一。本文对氧化应激在氟中毒脑损伤中的意义作出综述。     

Ascorbic acid attenuates cognitive impairment and brain oxidative stress in ovariectomized mice

Background

Menopause is associated with increased oxidative stress and memory impairment. Based on the antioxidant property of ascorbic acid (AA), It’s effect on cognitive function, the serum level of the brain-derived neurotrophic factor (BDNF) and the activity of antioxidant enzymes within the brain in ovariectomized (OVX) mice was investigated.

a-硫辛酸及缬沙坦对糖尿病肾病氧化应激的调节作用

目的 观察a-硫辛酸、缬沙坦对糖尿病肾病（DN）患者氧化应激的调节作用。方法186名志愿者被纳入研究,包括健康对照组40例、单纯糖尿病组38例（DM组）、DNa-硫辛酸治疗组35例（DNA组）、DN缬沙坦治疗组40例（DNX组）、DN联合治疗组（DNAX组）33例,对纳入对象进行血清超氧化物歧化酶（SOD）、总抗氧化能力（T—AOC）、丙二醛（MDA）、晚期蛋白氧化物（AOPP）含量及尿微量白蛋白排泄率（UAER）的测定,分析比较DN与氧化应激的相关性及a-硫辛酸、缬沙坦对糖尿病肾病的疗效与作用机制。结果与对照组相比,治疗前DM、DN组血清MDA（4．64±0．47、4．97±0．43）mol／ml、AOPP（45．28±5．99、70．80±12．40）μmol／L均显著升高,SOD（92．62±7．48、80．92±5．98）U／ml、T—AOC（8．17±0．94、7．19±0．73）U／ml均显著降低（p〈0．05）,以DN组最为明显,相关性分析显示UAER与MDA、AOPP呈正相关,与SOD、T—AOC呈负相关;治疗后DN各组血清MDA、AOPP及UAER较治疗前均显著降低,SOD、T—AOC显著升高（P〈0．05）,以DNAX组MDA（3．95±0．52）mol／ml、AOPP（61．79±11．08）umol／L、SOD（89．35±9．57）U／ml、T—AOC（7．95±0．77）U／ml变化最为显著。结论氧化应激参与人体糖尿病及糖尿病肾病的发生发展,仅一硫辛酸联合缬沙坦能够有效改善机体的氧化应激状态,改善DN预后。     

Inula crithmoides extract protects against ochratoxin A-induced oxidative stress, clastogenic and mutagenic alterations in male rats

Ochratoxin A (OTA) is a mycotoxin often found in cereals and agricultural products. There is unequivocal evidence of renal carcinogenicity of OTA in male rats, although the mechanism of action is unknown. Several reports suggest that exposure to OTA resulted in oxidative stress, genotoxicity and DNA damage. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Inula crithmoides growing in Egypt against OTA-induced mutagenicity and oxidative stress. Forty male Sprague-Dawley rats were divided into four groups and treated for 15 days as follows: control group and the groups treated with OTA (3mg/kg b.w), I. crithmoides extract alone (370mg/kg b.w) and OTA+I. crithmoides extract. Blood and tissue samples were collected for different biochemical analyses. Bone marrow micronucleus test and blood for random amplified polymorphism DNA-PCR (RAPD-PCR) method were performed to assess the antigenotoxic effect of the extract. The results indicated that OTA induced toxicological effects typical to those reported in the literature and increased the frequencies of MnPCEs in bone marrow. The RAPD-PCR analysis revealed the appearance of new bands in DNA resulting from genetic alteration. The extract alone was safe and succeeded in counteracting the oxidative stress and protect against the cytotoxicity resulting from OTA.     

Dihydrolipoic acid inhibits skin tumor promotion through anti-inflammation and anti-oxidation

α-Lipoic acid (LA) has been intensely investigated as a therapeutic agent for several diseases, including hepatic disorder and diabetic polyneuropathy. However, the effects of LA or its reduced form, dihydrolipoic acid (DHLA), on cancer chemoprevention has never been reported. In the present study, we examined the effects of DHLA/LA on the production of nitric oxide (NO) by inducible NO synthase (iNOS) and the formation of prostaglandin E2 (PGE₂) by cyclooxygenase-2 (COX-2), two important mediators associated with inflammation. DHLA/LA significantly inhibited lipopolysaccharide (LPS)-induced NO and PGE₂ formation in RAW 264.7 cells. Meanwhile, treatment with DHLA/LA suppressed the expression of iNOS protein but, unexpectedly, did not affect or increase the expression of COX-2 protein. The in vivo anti-inflammatory and antitumor-promoting activities were evaluated by a topical 12-O-tetradecanoylphorbol 13-acetate (TPA) application to mouse skin with measurement of edema formation, epidermal thickness and hydrogen peroxide production. DHLA significantly inhibited the priming and activation stages of skin inflammation induced by a double TPA application, by decreasing the inflammatory parameters. Furthermore, DHLA inhibited DMBA (0.3 μmol)/TPA (2.0 nmol)-induced skin tumor formation by reducing the tumor incidence and tumor multiplicity. When applied topically onto the shaven backs of mice prior to TPA, DHLA markedly inhibited the expression of iNOS protein. DHLA also strongly and directly inhibited COX-2 activity. These results suggest that DHLA can be a possible chemopreventive agent in inflammation-associated tumorigenesis.     

葛根素对油酸致急性肺损伤大鼠的保护作用

目的探讨葛根素对油酸致急性肺损伤大鼠的保护作用。方法24只健康雄性SD大鼠,完全随机分为5组：正常对照组,油酸组和葛根素干预组,各8只。通过静脉注射油酸建立大鼠急性肺损伤模型。正常对照组：大鼠静脉注射0．9％氯化钠溶液0．1ml／kg;油酸组：大鼠静脉注射油酸0．1ml／kg;葛根素干预组：大鼠在注射油酸前30min腹腔注射葛根素30mg／kg。光镜下观察大鼠肺组织形态学改变;检测血清中肿瘤坏死因子α（TNF-α）含量,肺组织中超氧化物歧化酶（SOD）活性和丙二醛含量。结果肺组织形态学变化提示葛根素干预组大鼠肺组织炎症反应较油酸组减轻。油酸组和葛概素干预组均较正常对照组大鼠血清中TNF—α含量增加、肺组织中SOD活性降低、丙二醛含量增加[分别为（41．7±3．4）、（19．0±1．3）ng／L比（5．8±0．8）ng／L;（78±6）、（93±7）U／mg比（113±9）U／mg;（11．89±0．64）、（7．87±0．81）μmol／g比（2．49±0．28）μmol／g]（均P〈0．05）;但葛根素干预组上述3项指标均优于油酸组（均P〈0．05）。结论葛根素对油酸致急性肺损伤大鼠具有一定的保护作用,其机制可能与提高大鼠抗氧化能力、降低血清中TNF—α含量有关。     

Curcumin protects rats against gentamicin-induced nephrotoxicity by amelioration of oxidative stress,endoplasmic reticulum stress and apoptosis

ContextGentamicin (GM) is an aminoglycoside antibiotic which is commonly used against Gram-negative bacterial infection; however, serious complications including nephrotoxicity could limit its clinical use.ObjectiveThe present study examined the protective effects of curcumin (CUR) on endoplasmic reticulum (ER) stress-mediated apoptosis through its antioxidative property in GM-induced nephrotoxicity in rats.Materials and methodsMale Sprague-Dawley rats (n = 3) were divided into six groups to receive normal saline (control), GM (100 mg/kg/day), co-treatment with GM and CUR (100, 200 and 300 mg/kg/day) and CUR (200 mg/kg/day) alone for 15 days by gavage feeding. Then, the renal function, kidney injury as well as oxidative stress, antioxidative markers and ER stress-mediated apoptosis were evaluated.ResultsPre-treatment of CUR rescued the nephrotoxicity in GM-treated rats. Several nephrotoxicity hallmarks were reversed in the CUR-pre-treatment group. At the dose of 200 mg/kg/day, it could significantly lower serum creatinine (from 0.95 to 0.50 mg/dL), blood urea nitrogen (from 35.00 to 23.50 mg/dL) and augmented creatinine clearance (from 0.83 to 1.71 mL/min). The normalized expression of oxidative stress marker, malondialdehyde was decreased (from 13.00 to 5.98) in line with the increase of antioxidant molecules including superoxide dismutase (from 5.59 to 14.24) and glutathione (from 5.22 to 12.53). Furthermore, the renal ER stress and apoptotic protein biomarkers were lowered in CUR treatment.Discussion and conclusionsOur findings pave the way for the application of CUR as a supplement in the prevention of nephrotoxicity and other kidney diseases in the future.     

Evaluation of 8-hydroxy-2-deoxyguanosine and NFkB activation,oxidative stress response,acetylcholinesterase activity,and histopathological changes in rainbow trout brain exposed to linuron

Linuron is a widely used herbicide to control grasses and annual broad leaf weeds. It is known that linuron has toxic effects on different organisms. However, the toxic effects of linuron on aquatic organisms, especially fish, is completely unknown. Thus, we aimed to investigate changes in 8-hydroxy-2-deoxyguanosine (8-OHdG) and nuclear factor kappa B (NFkB) activity, histopathological changes, antioxidant responses and acetylcholinesterase (AChE) activity in rainbow trout brain after exposure to linuron. Fish were exposed to 30 μg/L, 120 μg/L and 240 μg/L concentrations of linuron for twenty-one days. Brain tissues were taken from fish for 8-OHdG and NFkB activity, histopathological examination and determination of superoxide dismutase (SOD), catalase (CAT) enzyme activity, lipid peroxidation (LPO), and reduced glutathione (GSH) levels. Our data indicated that high linuron concentrations caused a decrease in GSH levels, SOD and CAT activities in brain tissues (p < 0.05). LPO levels were significantly increased by 240 μg/L linuron. All concentrations caused a significant inhibition in brain AChE enzyme activity (p < 0.05). Immunopositivity was detected for 8-OHdG and NFkB, and linuron exposure caused histopathological damage to the brain tissues. The results of this study can provide useful information for understanding of linuron-induced toxicity.     

Association of oxidative stress with arsenic methylation in chronic arsenic-exposed children and adults

Though oxidative stress is recognized as an important pathogenic mechanism of arsenic, and arsenic methylation capacity is suggested to be highly involved in arsenic-related diseases, the association of arsenic methylation capacity with arsenic-induced oxidative stress remains unclear. To explore oxidative stress and its association with arsenic methylation, cross-sectional studies were conducted among 208 high and 59 low arsenic-exposed subjects. Levels of urinary arsenic species [inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] were determined by hydride generation atomic absorption spectrometry. Proportions of urinary arsenic species, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were used as indicators for arsenic methylation capacity. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations were analyzed by enzyme-linked immunosorbent assay kits. Reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in whole blood were determined to reflect anti-oxidative status. The high arsenic-exposed children and adults were significantly increased in urinary 8-OHdG concentrations but decreased in blood GSH levels compared with the low exposed children and adults. In multiple linear regression models, blood GSH levels and urinary 8-OHdG concentrations of arsenic-exposed children and adults showed strong associations with the levels of urinary arsenic species. Arsenic-exposed subjects in the lower and the upper quartiles of proportions of urinary arsenic species, FMR or SMR were significantly different in urinary 8-OHdG, blood GSH and SOD. The associations of arsenic methylation capacity with 8-OHdG, GSH and SOD were also observed in multivariate regression analyses. These results may provide linkage between arsenic methylation capacity and oxidative stress in humans and suggest that adverse health effects induced by arsenic are related to arsenic methylation through oxidative stress.