Protective effects of vitamin C and curcumin against acrylamide toxicity in embryonic fibroblast cells

Abstract

Acrylamide is a highly soluble and widely produced industrial chemical that has been shown to pose numerous health hazards. This study aimed to assess the effects of acrylamide on the cytotoxicity and oxidative damage in embryonic fibroblast cells (BALB/c 3T3) and to measure protective roles of the natural antioxidants vitamin C and curcumin. Embryonic fibroblast cells were exposed to acrylamide at concentrations of 1, 10, 100, and 1000?μmol/L and vitamin C (50?μmol/L) or curcumin (2.5?μmol/L) for 24?h. Cell viability, cytotoxicity, the activities of antioxidant enzymes superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and catalase, and the markers of oxidative lipid peroxidation, hydroxyl radical, hydrogen peroxide and glutathione were measured. Co-treatment of the acrylamide-exposed fibroblast cells with vitamin C or curcumin attenuated the cytotoxicity and formation of reactive oxygen species and decreased the antioxidant enzyme activity. Thus, it was concluded that vitamin C and curcumin may play a protective role against acrylamide toxicity; the treatment with 50?μmol/L vitamin C was found to be more effective than the treatment with 2.5?μmol/L curcumin.     

Bromobenzene-induced hepatotoxicity in male rats: the protective effect of flaxseed

The metabolites of bromobenzene (BB) are hepatotoxic. The aim of this study was to determine the efficacy of different doses of flaxseed extract in alleviating BB-hepatotoxicity in male albino rats. Oxidative stress parameters, drug metabolizing enzymes, a pro-inflammatory marker, an apoptotic marker, and DNA fragmentation pattern were also assessed. Animals were divided into five groups treated by intragastric intubation as follows: control, BB-treated 460?mg?kg^?1?BW alone; three animal groups (III, IV, V) were treated concurrently with 460?mg?kg^?1 BB daily for 3 weeks and different doses of flaxseeds extract: 100, 200, or 300?mg?kg^?1?BW. Oral treatment of BB produced a significant decrease in activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase and glutathione levels, while activities of glutathione reductase and drug-metabolizing enzymes; glutathione-S-transferases and cytochrome P450 were enhanced. BB-treatment resulted in enhanced production of nitric oxide and activation of COX-2 and caspase-3. Pre-treatment with different doses of flaxseeds extract prior and during BB-treatment protected liver against BB-induced hepatotoxicity. The lower dose of flaxseed extract (100?mg?kg^?1) was most effective one.     

亚砷酸钠对酵母细胞抗氧化酶活性和脂质过氧化的影响

以模式生物酿酒酵母为材料,研究亚砷酸钠对细胞生长、抗氧化酶活性、丙二醛(MDA)含量及胞内活性氧(ROS)水平的影响。结果显示,加入亚砷酸钠(终浓度0.1~0.6 mmol·L~(-1))后,培养液在600 nm处的光密度值(OD600值)低于对照组,并呈浓度依赖性降低。经亚砷酸钠处理12 h后,酵母细胞中过氧化物酶(POD)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和总抗氧化能力(T-AOC)活性均增高,但胞内ROS水平和MDA含量与对照组无显著差异。砷处理24 h后,POD在0.2 mmol·L~(-1)砷处理组中活性最高,而CAT、SOD和T-AOC活性呈浓度依赖性增高;胞内ROS水平和MDA含量在高浓度砷组(0.4和0.6 mmol·L~(-1))显著增高。结果表明,亚砷酸钠可抑制酵母细胞生长,改变细胞内抗氧化酶活性,较高浓度时可引起细胞氧化损伤。     

EEDs对鱼类性激素合成途径干扰作用研究进展

环境内分泌干扰物(environmental endocrine disruptors,EEDs)是一类可以改变生物体内激素的合成、释放、运输、代谢、结合、作用或清除等一系列生物过程的外源物质。性激素的生物合成需要一系列酶的参与,体内和体外研究表明,性激素合成途径中的类固醇生成酶是EEDs通过非性激素受体介导途径发挥内分泌扰乱作用的重要靶点,性激素合成途径的扰乱可能导致生物体生殖系统受损。本文综述了EEDs对鱼类性激素合成底物和类固醇生成酶的影响、信号转导机制及其生殖危害;并对性激素合成途径中促性腺激素调控机理、多种转录因子间的相互作用、不同物种间类固醇生成酶的差异以及各内分泌轴线的相互作用研究进行了展望,以期为EEDs通过非性激素受体介导途径发挥内分泌干扰效应的机制研究提供思路。     

Antioxidant enzymatic activities and lipid peroxidation in liver and ovary of zebrafish (Danio rerio) exposed to deltamethrin

Deltamethrin (DM) is being used as a substitute for organochlorines and organophosphates in pest control because of its low environmental persistence and toxicity. But it has become an environmental contaminant as it has been used widely. In this study, we investigated the effect of DM (technical grade) on the antioxidant system of adult zebrafish. For this, six-month-old fish were exposed to 2, 4 and 6?μg/L of DM for 96?h. The tissues selected were liver and ovary. Our data showed that exposure to DM increases CAT (catalase), SOD (superoxide dismutase), GPx (glutathione peroxidase, antioxidant enzymes), LPO (lipid peroxidation, non-enzymatic antioxidant) and GST (glutathione S-transferase, detoxifying enzyme) in liver and ovary. Increased GST could detoxify the toxicant; still there could be enough DM to cause oxidative stress. It appears from our study that zebrafish used compensatory mechanisms in eliminating reactive oxygen species. These data will be useful as oxidative stress is being used as a biomarker for aquatic pollution.     

Impact of environmental concentrations of beta-cypermethrin on the antioxidant system in the brain and liver of zebrafish (Danio rerio)

Beta-cypermethrin (beta-CYP) is a widely used pyrethroid pesticide, the extensive application of which may potentially cause damage to non-target organisms. To investigate the effect of beta-CYP on the antioxidant system of aquatic animals, adult zebrafish were exposed to environmentally relevant dosages (0.01, 0.1 and 1.0 μg/L) of beta-CYP. The activities of four antioxidant enzymes in zebrafish liver and brain tissue were tested after 7, 15 and 30 days of exposure. Our results showed that exposure of beta-CYP could induce different levels of increase in hepatic superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) activities at 7 and 15 days post exposure (dpe), but caused apparent inhibition of hepatic SOD, GR and GPx activities at 30 dpe. Unlike in liver tissue, SOD and CAT activities in zebrafish brain did not show any apparent response to beta-CYP during the whole treatment period. In addition, increased brain GPx activities were observed at 7 and 30 dpe.     

Dichloroacetate- and trichloroacetate-induced modulation of superoxide dismutase,catalase, and glutathione peroxidase activities and glutathione level in the livers of mice after subacute and subchronic exposures

Dichloroacetate (DCA) and trichloroacetate (TCA) were previously found to induce various levels of oxidative stress in the hepatic tissues of mice after subacute and subchronic exposures. The cells are known to have several protective mechanisms against production of oxidative stress by different xenobiotics. To assess the roles of the antioxidant enzymes and glutathione (GSH) in DCA- and TCA-induced oxidative stress, groups of B6C3F1 mice were administered either DCA or TCA at doses of 7.7, 77, 154, and 410 mg kg^?1 day^?1, by gavage for 4 weeks (4-W) and 13 weeks (13-W), and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as GSH were determined in the hepatic tissues. DCA at doses ranging between 7.7–410, and 7.7–77 mg kg^?1 day^?1, given for 4-W and 13-W, respectively, resulted in either suppression or no change in SOD, CAT, and GSH-Px activities, but doses of 154–410 mg DCA kg^?1 day^?1 administered for 13-W were found to result in a significant induction of the three enzyme activities. TCA administration on the other hand, resulted in increases in the SOD and CAT activities, but caused suppression of GSH-Px activity in both the periods. Except for the DCA doses of 77–154 mg kg^?1 day^?1 administered for 13-W that resulted in a significant reduction in the GSH levels, all other DCA as well as TCA treatments produced no changes in GSH. Since these enzymes are involved in the detoxification of the reactive oxygen species (ROS), superoxide anion (SA), and H₂O₂, it is concluded that SA is the main contributor to DCA-induced oxidative stress, while both ROS contribute to that of TCA. The increase in the enzyme activities associated with 154–410 mg DCA kg^1? day^?1 in the 13-W period suggest their role as protective mechanisms contributing to the survival of cells modified in response to those treatments.     

Protective effects of Flacourtia indica on doxorubicin-induced cardiotoxicity in rats

This study examined the cardioprotective activity of an ethanolic extract of Flacourtia indica (FI) against doxorubicin (DOX)-induced myocardial infarction (MI) in rats. Different phytoconstituents were identified by gas chromatography-mass spectroscopy. DOX is a chemotherapeutic agent which produces free oxygen radicals that result in serious dose-limiting cardiotoxicity. A DOX dose of 20?mg?kg^?1 body weight is used to bring significant changes in biochemical parameters, endogenous antioxidants, and moderate necrosis in the heart. The pretreatment with FI at two doses (250 and 500?mg?kg^?1) to DOX-treated rats significantly prevented the altered biochemical parameters such as serum marker enzymes serum glutamate-pyruvate transaminase, serum glutamate oxaloacetate transaminase, creatine phosphokinase, and lactate dehydrogenase, lipid profile such as low-density lipoprotein, very low-density lipoprotein, triglycerides, high-density lipoprotein, total cholesterol, and antioxidant parameters such as superoxide dismutase, glutathione, catalase, glutathione peroxidase, and malondialdehyde to near normal level. Serum urea, uric acid, and alkaline phosphate which are increased on DOX administration registered near normal values on pretreatment with FI. In conclusion, these data suggest that the ethanol extract of FI can prevent heart damage by DOX-induced MI in rats and this is likely mediated through its antioxidant activities.     

三邻甲苯磷酸酯对大鼠C6星形胶质细胞的氧化损伤和细胞周期阻滞作用

三邻甲苯磷酸酯(tri-o-cresyl phosphate,TOCP)是一种有机磷酸酯类化合物,具神经毒性作用。研究表明星形胶质细胞是有机磷化合物(organophosphorus compounds,OPs)神经毒性作用的靶点之一。为了探讨TOCP对星形胶质细胞的毒性作用,采用大鼠C6星形胶质细胞分别经0.1、0.3、1.0和3.0 mmol·L-1TOCP染毒处理24 h,应用MTT比色法和乳酸脱氢酶(LDH)活力分析法检测细胞活力,在电子相差显微镜下观察细胞形态,二硫代二硝基苯甲酸(DNTB)比色法测定谷胱甘肽(GSH)含量和谷胱甘肽过氧化物酶(GSH-Px)活性,流式细胞仪检测分析细胞周期。结果显示,经TOCP处理24 h后,大鼠C6星形胶质细胞存活率降低,LDH释放增加,细胞形态也发生了明显的变化。GSH含量和GSH-Px活性降低,G1期细胞数量也逐渐增加。上述结果表明,TOCP对星形胶质细胞具有毒性作用,引起氧化损伤和细胞周期阻滞。     

消油剂与120#燃料油对马粪海胆(Hemicentrotus pul-cherrimus)抗氧化酶活性的影响

在溢油事故应急处置中,消油剂的使用备受争议。为探究消油剂和溢油对海洋底栖模式生物海胆(Hemicentrotus pulcherrimus)复合毒性效应,通过WAFs(Water-accommodated fractions)和CEWAFs(Chemically enhanced water-accommodated fractions)的96 h暴露实验,测定海胆肠和性腺中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽硫转移酶(GST)、谷胱甘肽过氧化物酶(GPx)活性的变化。实验结果表明:随油水配比浓度的增加,4种酶活性呈现先升高后降低趋势,且酶活性峰值均极显著高于海水对照组水平(P0.01)。肠中4种酶活性最大诱导倍数均高于性腺。相同暴露浓度下,CEWAFs组4种酶活性诱导程度均高于WAFs组。消油剂对照组和海水对照组间4种酶活性则无显著性差异(P0.05)。     

铅与纳米SiO2联合染毒对A549细胞氧化损伤的影响

为了研究铅与纳米SiO2联合染毒所致的细胞损伤特征,并从氧化应激方面探讨其可能的作用机制。用铅和SiO2处理A549细胞,采用四唑盐(MTT)比色法检测细胞存活率,评价铅和SiO2联合染毒所致的细胞损伤特征;采用硫代巴比妥酸(TBA)比色法检测细胞内丙二醛(MDA)含量,评价铅与SiO2联合染毒所致细胞的氧化应激状态;检测了细胞内抗氧化物还原型谷胱甘肽(GSH)含量以及细胞内抗氧化酶的活性,以评价铅与SiO2联合染毒对细胞抗氧化系统的影响。将实验数据进行ANOVA分析。结果表明,铅、SiO2单独染毒组各指标没有明显改变;而联合染毒能造成细胞氧化损伤,表现为细胞存活率、GSH水平、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性显著低于对照组及2个单独染毒组(P<0.05),细胞内MDA含量显著高于对照组及各单独染毒组(P<0.05)。可见,联合染毒可引起明显的细胞毒性,氧化损伤可能是铅与SiO联合染毒致肺细胞毒性损伤的作用机制之一。     

Protective effects of Manasamitra vatakam on aluminum-induced nephrotoxicity,oxidative stress,and histological damage

The aim of this study was to investigate the nephroprotective and antioxidant property of Manasamitra vatakam (MMV) against aluminum (Al)-induced toxicity in rats. The kidney function marker parameters such as serum urea, uric acid, and creatinine were significantly increased in Al-treated rats as compared with controls. Similarly, the antioxidant enzyme activities such as superoxide dismutase, glutathione S-transferase, Na⁺/K⁺-ATPase and Mg-ATPase, reduced glutathione were also found significantly increased in Al-treated rats. A significantly decreased level of these parameters was observed in the MMV (orally 100?mg?kg^?1 body weight)-treated group along with a reduced level of malonaldehyde, molecular chaperones of an antioxidative stress protein, and mRNA expression of HSP70. The biochemical observations were also supported by histopathological observations. Thus, this study supports the nephroprotective and antioxidant activities of MMV.     

Occurrence and distribution of antioxidant enzymes in the haemolymph of the shore crab Carcinus maenas

The haemocytes and cell-free haemolymph of the shore crab Carcinus maenas were examined for the presence of the antioxidant enzymes, catalase (EC 1.11.1.6), glutathione peroxidase (GPX) (EC 1.11.1.9) and superoxide dismutase (SOD) (EC 1.15.1.1) by biochemical assay and immunocytochemistry. The results show that all three enzymes are present in the haemocytes, but vary in distribution and amount. Catalase was detected principally in the phagocytic hyaline cells, whereas GPX and SOD were found in both the hyaline and granular cells. Catalase and glutathione peroxidase activities were absent from the semi-granular cells, and although SOD was detected in some samples, there was enormous variation in the level of this enzyme between individuals. Cell-free haemolymph, by contrast, was found to be positive for GPX and SOD but lacked catalase activity. Immunocytochemical analyses further showed that only 2 to 16% of the cells stain positively for these enzymes, and where present the enzymes tended to be distributed throughout the cytoplasm. With the granular cells, however, there was some localization of GPX and SOD around the granules. Since the phagocytes of C. maenas are known to produce superoxide anion radicals, hydrogen peroxide, and possible other reactive oxygen species upon stimulation with phorbol myristate acetate, lipopolysaccharide, or concanavalin A in vitro, it is likely that catalase, GPX and SOD are present in the haemolymph to assist in protection of the host tissues against oxyradical damage during host defence in vivo.     

乙酸铜对银鲳幼鱼急性毒性及抗氧化酶活性的影响

为评价乙酸铜对银鲳的安全性及毒性效应,采用静水急性暴露实验,研究了8个乙酸铜浓度梯度(0、0.150、0.206、0.282、0.387、0.531、0.729、1.00 mg·L~(-1))对银鲳幼鱼的急性毒性,以肝脏和鳃组织的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化酶(GSH—PX)以及谷胱甘肽巯基转移酶(GST)活性为指标研究乙酸铜对银鲳幼鱼的毒理作用,并进行安全评价。结果表明,高浓度乙酸铜会对银鲳幼鱼产生了较大的毒性,48 h和96 h-LC_(50)分别为0.898 mg·L~(-1)、0.264 mg·L~(-1),安全质量浓度为0.026 mg·L~(-1);不同浓度乙酸铜胁迫下银鲳幼鱼组织中的SOD、CAT、GSH-PX和GST活性均表现为低浓度被诱导而高浓度受抑制的规律,与乙酸铜浓度呈抛物线型剂量效应关系,此外,肝脏中4种抗氧化酶活性普遍高于鳃组织。研究发现,乙酸铜胁迫对抗氧化酶的影响,可以反映银鲳幼鱼机体的受损状况,其中SOD可较灵敏地指示早期低浓度的铜污染。     

Sodium cyanide-induced modulations in the activities of some oxidative enzymes and metabolites in the fingerlings of Cyprinus carpio (Linnaeus)

Carp fingerlings exposed to a sublethal concentration (0.5?mg?L^?1) of sodium cyanide showed a steady decrement over a 7-day period in respiratory rate, rise in lactate dehydrogenase (LDH), and fall in succinate dehydrogenase (SDH) activities followed by variations in lactic and pyruvate levels. Changes in these enzyme activities might be due to impaired oxidative metabolism and severe cellular damage leading to the release of these enzymes. Decline in the activities of SDH and LDH clearly represents a shift from aerobic to anaerobic metabolism as evidenced by elevated lactate and decline in pyruvate levels. The shift to anaerobic metabolism is also reflected by severe drop in the respiratory rate of the fish. This may be a consequence of the blockage of electron transfer from cytochrome c oxidase to molecular oxygen, thus ceasing cellular respiration and it can lead to cellular hypoxia even in the presence of normal hemoglobin oxygenation. Hence, we indirectly reconfirm the inhibition of oxidative metabolism by sodium cyanide. Alterations in behavioral pattern induced by sublethal sodium cyanide exposure may be due to the combination of cytotoxic hypoxia with lactate acidosis, which depresses the central nervous system (CNS); as the brain is the most sensitive site to anoxia, it results in impaired CNS function.     

Effects of paint particles inhalation on superoxide dismutase and glutathione peroxidase activities in industrial painters

The aim of this study was to examine effects of lead (Pb)-based paints on malondialdehyde (MDA) levels as an indicator for lipid peroxidation; and on activities of serum antioxidant enzymes activities such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) in industrial painters. A total of 67 male painters and 50 age-matched and gender-matched controls were included in this cross-sectional study. There were 19 smokers and 48 non-smokers in the paint-exposed group and 20 smokers and 30 non-smokers in the control group. Hemoglobin concentrations were lower in painters’ blood compared to controls. The blood Pb concentrations were higher in painters compared to controls. SOD and GPx activities were significantly lower in painters compared to controls. MDA concentration was found to be significantly elevated. Smoking was found to be a major confounder. Data suggest that Pb-based paints affect oxidant parameters in occupationally exposed workers.     

Vitamin E-mediated protection on methomyl-induced alterations in rat liver

The present study was carried out to observe the possible beneficial effects of Vitamin E, a natural antioxidant on methomyl-induced biochemical and histological alterations in rat liver. To carry out the investigations, animals were segregated in four different groups. Animals in Group I served as normal controls. Animals in Group II were given single methomyl dose orally in water (9 mg kg^?1 b.wt). Animals in Group III were injected intraperitoneally with Vitamin E (50 mg kg^?1 b.wt) for 1 week on alternate days. Animals in Group IV were administered Vitamin E 1 week before subjecting them to methomyl treatment. Animals in all the groups were sacrificed 24 h after the end of treatments. Different biochemical estimations were carried out, which included estimation of aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP) and acetylcholinesterase (AChE). Further, to examine the oxidative damage lipid peroxidation (LPO) and glutathione (GSH) levels as well as antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GSHPx), and glutathione-6-phosphate dehydrogenase were estimated in liver samples. AchE activity was inhibited significantly both in serum and liver following methomyl treatment. Administration of methomyl caused a significant increase in serum AST, ALT and ALP which indicated hepatic damage. LPO was found to be significantly increased, whereas GSH levels were decreased in the liver of methomyl-treated animals. The activities of SOD and catalase were significantly decreased whereas GST and GSHPx activities were found to be elevated significantly following methomyl treatment. No significant change in the enzyme activity of GR and glutathione-6-phosphatase dehydrogenase was observed after methomyl treatment. Vitamin E supplementation was able to attenuate appreciably the methomyl-induced changes in LPO levels along with SOD and GST activities. Histopathological studies following methomyl treatment revealed that hepatocytes, were not very well delineated and nuclei showed degenerative changes. Whereas, following Vitamin E supplementation in combined treatment group nuclei showing degenerative changes become less in number. The study, therefore, concludes that Vitamin E has a potential in mitigating most of the adverse effects induced by methomyl acute toxicity.     

Effects of Matricaria chamomilla L. on lipid peroxidation,antioxidant enzyme systems,and key liver enzymes in CCl4-treated rats

In this study, we investigated the effects of Matricaria chamomilla L. extract (MCE) on lipid peroxidation, antioxidant enzyme systems, and several liver enzymes in carbon tetrachloride (CCl₄)-treated rats. Rats were divided into five groups. The first group (control group) was fed on standard feed. The rats in the other groups (CCl₄, MCE50, MCE100, and MCE200) were injected intraperitoneally with 0.8?mL?kg^?1 CCl₄. Moreover, rats in the MCE50, MCE100, and MCE200 groups were gavaged with 50?mg?kg^?1, 100?mg?kg^?1, and 200?mg?kg^?1 MCE, respectively. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, whole blood malondialdehyde (MDA) and glutathione (GSH) levels, and erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activity levels were measured after 14 days of exposure. ALT and AST in the CCl₄ group increased significantly in comparison to the control group (p?4, MCE50, MCE100, and MCE200 groups at different significance levels. In conclusion, the findings suggest that, depending on the dose administered, MCE decreases CCl₄-induced damage and consequent oxidative stress in rats; it affects the antioxidant system positively.