Influence of diet,vitamin, tea,trace elements and exogenous antioxidants on arsenic metabolism and toxicity

Health risk of arsenic (As) has received increasing attention. Acute and chronic exposure to As could cause several detrimental effects on human health. As toxicity is closely related to its bioaccessibility and metabolism. In real environment, many factors, such as diet and nutrition, can influence As bioaccessibility, metabolism and toxicity. This paper mainly reviews the influences of diets and elements on As bioaccessibility, metabolism and toxicity and their underlying mechanisms to provide suggestions for future investigations. Vitamins, jaggery, fruit, tea, glutathione, N-acetylcysteine and zinc could reduce the As-induced toxicity by increasing antioxidative enzymes to antagonize oxidative stress caused by As and/or increasing As methylation. However, bean and betel nut could increase risk of skin lesions caused by As. Interestingly, high-fat diet, selenium and iron have incompatible effects on As bioaccessibility, metabolism and toxicity in different experimental conditions. Based on current literatures, the As methylation and As-induced oxidative damage might be two main ways that the diets and elements influence As toxicity. Combined application of in vitro human cell lines and gastrointestinal models might be useful tools to simultaneously characterize the changes in As bioaccessibility and toxicity in the future research.     

Dietary selenium fortification: a potential solution to chronic arsenic toxicity

Selenium (Se), an important micronutrient and antioxidant, also acts as an antagonist of arsenic (As). Se supplementation of diet was investigated in mitigating chronic As toxicity in mammals. Experiments were conducted to determine whether Se supplementation in As-exposed rats might (i) decrease As-induced lipid peroxidation in liver, (ii) increase blood antioxidant status, and (iii) reverse suppression of the secondary antibody response. Male Wistar rats were exposed to As (40 and 80?ppm) in drinking water and received challenge diets with three different levels of Se (deficient: <0.01?ppm, adequate: 0.15 ppm, and fortified: 0.6?ppm) for 16 weeks. Clinical variables including behavior, body weight, and food and water consumption were recorded weekly, and blood sample was collected monthly. Antioxidant status was assessed through glutathione sulfhydryl (GSH) levels in whole blood. Lipid peroxidation in the liver was evaluated using the malondialdehyde (MDA) assay. The antibody response was measured using keyhole limpet hemocyanin as an immunogen. Se deficiency significantly increased hepatic lipid peroxidation and suppressed antibody production relative to the Se-adequate and -fortified groups, confirming that Se deficiency exacerbates the damage produced by As exposure. Se fortification markedly elevated the blood GSH level in both As-exposed groups, indicating protective effects. At adequate Se levels, rats showed signs of counteracting As-mediated toxicity. However, Se fortification produced more pronounced benefits against As-induced toxicity, a pattern that was particularly notable in the 40?ppm As group.     

DNA fragmentation,apoptosis and cell cycle arrest induced by sodium arsenite in cultured murine Sertoli cells: prevention by curcumin

Arsenic is a significant environmental concern worldwide, primarily due to geo physiochemical contamination of drinking water, and a major public health hazard in both developing and developed countries. The present study was aimed to investigate ameliorative effects of curcumin (Cur) against sodium arsenite (SA)-induced toxicity in cultured murine Sertoli cells. The cells were treated with SA (5 μM) and Cur (5 μg/ml and 10 μg/ml) alone or in combination for 12 hr. The SA treatment decreased cell viability, produced oxidative stress, and induced apoptosis as reflected by reactive oxygen species (ROS) generation, loss of mitochondrial transmembrane potential, DNA fragmentation, and apoptotic cells. Moreover, the SA-induced cell cycle arrest in the cells is characterized by a rise in the number of cells in the sub G1 phase of the cell cycle. The Cur was found to be effective in reversing all these arsenic (As)-induced cellular events. Data suggest that Cur modulates As-mediated oxidative stress, apoptosis, DNA fragmentation, and cell cycle arrest through suppression of excessive ROS generation. Evidence indicates that Cur may emerge as a useful protective agent against As-induced Sertoli cells toxicity by inhibiting As-induced damage in testes.     

Antidiabetic effects of Trigonella foenum-graecum seed powder in a rat model

Free radical production and oxidative stress are known to increase in liver during diabetes and may contribute to oxidative damage. In this study, the effect of oral feeding of Trigonella foenum-graecum seed powder (TSP) has been studied on blood glucose, membrane-linked ATPases, antioxidant enzymes, lipid peroxidation, lipofuscin content and membrane fluidity in livers of a diabetic rat. Diabetes was induced by administration of alloxan monohydrate. Hyperglycemia during diabetes has been shown to entail free radical generation, with a concomitant increase in lipid peroxidation and lipofuscin content, inhibition of membrane-linked ATPases, increased antioxidant enzyme activities and decreased membrane fluidity. TSP treatment reverses the changes to near normal levels thereby ameliorating the management of diabetic complications.     

Oleuropein alleviates malathion-induced oxidative stress and DNA damage in rats

The effects of acute exposure to 250 mg/kg malathion and the protective effects of 20 mg/kg oleuropein, both administered intraperitoneally, were evaluated in Wistar male rats. Malathion administration increased malondialdehyde, nitric oxide, 8-hydroxy-2′-deoxyguanosine, total oxidant status, and DNA damage, yet decreased total antioxidant activity, superoxide dismutase, and catalase activities in blood, liver, and kidney. Administration of oleuropein reversed malathion-induced oxidative stress, lipid peroxidation, DNA damage, and antioxidant enzyme activity.     

Antioxidant enzymes and compounds complement each other during arsenic detoxification in shoots of Isatis cappadocica Desv.

Isatis cappadocica has been reported to be an arsenic (As) hyperaccumulator. Antioxidant enzymes and compounds have been proposed to play an important role in the detoxification and tolerance of As. In the present study, As-induced oxidative stress and antioxidant responses were investigated on I. cappadocica grown hydroponically in response to application of arsenate (0–1200?μmol). As accumulation increased with an increase in arsenate concentration in the medium. Along with a significant increase in arsenate concentration, a build up in hydrogen peroxide, indicators of oxidative stress, was observed. The activity of superoxide dismutase and peroxidase was induced after arsenate treatment, reached a maximal value at 800?μmol arsenate and then declined at the highest arsenate treatment. Glutathione reductase activity and contents of non-enzymatic antioxidants (carotenoids, flavonoids and anthocyanins) increased significantly as arsenate concentration augmented. These results indicated that high efficient antioxidant system may play significant roles in As detoxification and improve I. cappadocica tolerance against As toxicity.     

Effects of subchronic exposure to carbofuran on antioxidant defence system and malondialdehyde levels in common carp (Cyprinus carpio L.)

The present study focused on the assessment of oxidative stress induction by pesticides such as carbamates which are widely used as insecticides and nematicides and contaminate aquatic ecosystems on certain biomarkers in liver of common carp (Cyprinus carpio L.). Biomarkers selected for stress monitoring were malondialdehyde (MDA), an index of lipid peroxidation, and antioxidant defence system enzymes, mainly catalase (CAT), glutathione reductase (GR), and glutathione-S-transferase (GST) activities in liver of fish exposed to 0, 10, 50, or 100?µg?L^?1 of carbofuran for 4, 15, or 30 days. Oxidative stress was found in liver of common carp exposed to carbofuran which was manifested by a decrease in CAT and GR activities after 4 and 30 days of exposure. An adaptive response was probably produced since at day 15 no modifications in the CAT activity and increased GR activity were observed. In addition, a decrease in MDA content with the highest concentration of carbofuran used was found after 30 days of exposure. However, no significant changes were found in GST activity showing a varied response. The results concerning oxidative and antioxidant profiles indicate that subchronic exposure to the insecticide carbofuran is capable of inducing oxidative stress in fish.     

Effects of salinity stress on neurotransmission, energy metabolism, and anti-oxidant biomarkers of Carcinus maenas from two estuaries of the NW Iberian Peninsula

This study investigated the effects of salinity on biomarkers of oxidative stress, energy metabolism, and neurotransmission of Carcinus maenas from an estuary low impacted by pollution and from an estuary under chemical stress in the NW Iberian Peninsula. Crabs were collected in the field and, following an acclimation period, they were exposed for 7 days to five salinity levels ranging from 4 to 45 psu. At the end of the exposure period, stress biomarkers were determined in samples of muscle and digestive gland. The biomarkers assessed in the muscle were the activities of the enzymes cholinesterases (ChE), of which acetylcholinesterase is involved in neurotransmission, and lactate dehydrogenase (LDH) and isocitrate dehydrogenase (IDH) that are involved in energy metabolism. The biomarkers assessed in the digestive gland were (1) the activities of the enzymes glutathione S-transferases (GST), glutathione reductase (GR), and glutathione peroxidase (GPx), involved in phase II biotransformation and the anti-oxidant defence system; (2) the levels of total glutathiones (TG), also belonging to the anti-oxidant system; and (3) the levels of lipid peroxidation as a measure of oxidative damage. The results showed a significant influence of salinity on neurotransmission, energy metabolism, anti-oxidant status, and oxidative damage of C. maenas. For some biomarkers, this influence was dependent on whether the crabs were collected at the low-polluted estuary or at the contaminated estuary. In particular, crabs collected at the low-polluted estuary showed altered neurotransmission and anti-oxidant defences (GR). Crabs collected at the impacted estuary showed alterations in neurotransmission, energy metabolism (IDH and LDH), biotransformation, and anti-oxidant defences (GST, GR, GPx, and TG), as well as in oxidative damage, indicating that salinity change superimposes higher stress on these organisms. For ChE, IDH, and TG, altered responses were induced by both hypo- and hypersalinity.     

Involvement of mitochondrial-mediated caspase-3 activation and lysosomal labilization in acrylamide-induced liver toxicity

Acrylamide (ACR) is a chemical frequently used in both industrial and synthetic processes and may be produced during food processing. ACR at very high concentrations is postulated to exert its toxicity through the stimulation of an oxidative stress. ACR in excessive doses induces the central nervous system, reproduction, and genetic toxicity. However, ACR effects on the liver, a major organ of drug metabolism, have not been adequately explored. In addition, the role of mitochondria in an ACR-mediated hepatotoxicity is still unclear. The aim of this study was to investigate the cytotoxic mechanisms attributed to ACR using isolated rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method and incubated with an EC50_2hr concentration of ACR for 3 hr. The EC50_{2 hr} of ACR on isolated rat hepatocytes was determined to be 1 mM. Based on our results, hepatocytes cytotoxicity of ACR (1 mM) was mediated by a reactive oxygen species formation and lipid peroxidation. Incubation of hepatocytes with ACR produced rapid hepatocyte glutathione depletion which is another marker of the cellular oxidative stress. ACR cytotoxicity was also associated with mitochondrial injury as evidenced by the decline of mitochondrial membrane potential and lysosomal membrane leakiness. Our results also showed that ACR induced caspase-3 activation, the final mediator of apoptosis signaling. These findings contribute to a better understanding underlying mechanisms involved in ACR hepatotoxicity originating from the oxidative stress and ending in mitochondrial/lysosomal damage and cell death signaling.     

Bisphenol S induces oxidative stress and DNA damage in rat spermatozoa in vitro and disrupts daily sperm production in vivo

Bisphenol S has been introduced into some industrial applications and it may act as a xeno-estrogen that can alter endocrine functions and reproduction. The present study was carried out to examine the effect of bisphenol S exposure on oxidative stress, generation of reactive oxygen species, and DNA integrity in rat spermatozoa in vitro and daily sperm production and sperm DNA damage in vivo. Sperm were incubated with bisphenol S at concentrations of 0.5, 1, 10, and 100 µg/L. At the highest concentration, bisphenol S induced formation of reactive oxygen species, caused lipid peroxidation, affected superoxide dismutase levels, and increased DNA fragmentation. Adult rats were exposed to doses of 0.5, 5, 25, and 50 µg/kg/d for 28 days. Decrease in daily sperm production and an increase in sperm DNA damage was observed at the highest dose in the 50 µg/kg/d treated group, but sperm motility was not reduced.     

Antioxidant role of ascorbic acid on oxidative stress induced by sub-acute exposure of lead and cypermethrin in erythrocytes of Wistar rats

This study aimed to evaluate the reparative potential of ascorbic acid (AA, 100 mg/kg, orally for 28 days) in sub-acute lead (Pb, 100 ppm in drinking water for 28 days) or cypermethrin (CPM, 50 mg/kg, orally in vehicle for 28 days) poisoning alone and as binary mixture on the basis of oxidative stress parameters in erythrocytes of Wistar rats. Both Pb and CPM produced significant increase in lipid peroxidation along with elevated glutathione-S-transferase and catalase activity individually but not as a binary mixture. Glutathione peroxidase activity was significantly increased but glutathione levels were significantly reduced irrespective of single or co-exposure while the activity of superoxide dismutase and erythrocytic protein content were not significantly affected. Co-exposure led to a comparatively lower level of oxidative stress than that induced by Pb or CPM alone indicating an antagonistic toxicodynamic profile in rat erythrocytes. Co-administration of AA along with Pb and/or CPM significantly restored the oxidative stress parameters to normal values. Overall results indicated that co-exposure induces a lower level of oxidative stress and AA ameliorates Pb- and/or CPM-induced oxidative damage in rat erythrocytes.     

不同价态无机砷对罗非鱼肝脏砷积累及GSH/GST解毒代谢的影响

低剂量中长期暴露下的氧化胁迫是砷对水生生物致毒的重要机制之一。本文通过对罗非鱼进行32 d的食物相砷暴露,测定不同时间点罗非鱼肝脏中谷胱甘肽(glutathione,GSH)含量和谷胱甘肽巯基转移酶(glutathione S-transferase,GST)活性,揭示不同价态无机砷对罗非鱼肝脏中GSH/GST的影响机制。经三价砷(As(III))暴露后,砷含量在2 d内显著增加而在随后的30 d内无显著性差异; 0～2 d内GSH含量显著增加,后降低,13 d后GSH含量均低于空白组; 0～6 d GST活性均大于空白组,6～8 d GST活性降低,8 d后活性高于空白组,且32 d达到最大值。经五价砷(As(V))暴露后,罗非鱼肝脏中砷含量逐渐增加,在20 d时达到最大值而后无显著性差异; 0～2 d时GSH含量降低,随后逐渐增加,在16 d达到最大值,16 d后GSH含量均低于空白组; 0～8 d时GST被大量诱导合成,8～20 d时GST合成被抑制,20 d后活性增加,在32 d达到最大值。As(III)和As(V)对罗非鱼GSH/GST的不同影响与其在罗非鱼体内的积累量有关。As(III)暴露后各时间点罗非鱼肝脏中的砷含量与GSH含量呈统计学正相关,而As(V)暴露无明显相关性。这是因为As(V)进入罗非鱼肝脏后会还原为As(III),进而GSH作为可提供巯基的还原剂而被大量消耗。另外,As(III)暴露后各时间点罗非鱼肝脏中的砷含量与GST活性呈显著负相关,而As(V)暴露却呈现出很强的滞后性,这是由于进入生物体内的As(V)需转化为As(III)后,才可直接作用于酶系统。可见,不同形态砷对水生生物的致毒机制需进一步深入研究。     

Antimony induces oxidative stress and cell death in normal hepatocytes

Antimony (Sb) accumulates in the liver which is one of the target organs for metal-mediated toxicity. Although toxicity of Sb was previously investigated, the precise mechanism of Sb-induced hepatotoxicity remains to be determined. The aim of this study was to examine the role of oxidative stress, and mitochondria in the induction of cell death by Sb. Our results showed that liver cell lysis induced by Sb is mediated by reactive oxygen species (ROS) formation, lipid peroxidation and decline of mitochondrial membrane potential (MMP). Antimony-induced ROS formation, lipid peroxidation and reduction of MMP were significantly diminished by antioxidants and ROS scavengers such as dimethyl sulfoxide and mannitol; mitochondrial permeability transition (MPT) pore sealing agents such as carnitine and trifluoperazine; and adenosine triphosphate (ATP) generator, L-glutamine. Antimony-induced ROS formation, lipid peroxidation and fall in MMP were potentiated by glutathione (GSH) depletion via n-bromoheptane. MPT pore sealing agents and ATP generator inhibited hepatotoxicity, indicating Sb-activated cell death via mitochondrial pathway. Pretreatment of hepatocytes with antioxidants and ROS scavengers also blocked cell death induced by Sb, whereas GSH depletion enhances Sb-induced cell death, suggesting that oxidative stress may be directly involved in the reduction of MMP. These findings contribute to a better understanding of the mechanisms that mediate Sb-induced cell death in isolated rat hepatocytes.     

纳米ZnO对鲫鱼肝脏的毒性

鲫鱼(Carassius auratus)腹腔注射不同浓度纳米ZnO(5mg·kg-1、12.5mg·kg-1、25mg·kg-1、50mg·kg-1和125mg·kg-1,以鲫鱼体重计)14d后,研究了鲫鱼肝脏中的自由基(ROS)强度变化、氧化应激反应及其毒性机制.结果表明:纳米ZnO显著诱导鲫鱼肝脏自由基产生;自由基信号强度和脂质过氧化物(MDA)随纳米ZnO浓度的升高呈先升高后降低趋势;而还原型谷胱甘肽(GSH)含量和GSH/GSSG随纳米ZnO浓度的升高呈先降低后升高趋势;纳米ZnO的毒性主要表现在引起鲫鱼肝脏氧化损伤,其毒性机制为诱导鲫鱼肝脏产生活性氧自由基.     

Ameliorated effects of garlic (Allium sativum) on biomarkers of subchronic acrylamide hepatotoxicity and brain toxicity in rats

Acrylamide (ACR) exerts its toxicity through stimulation of the oxidative stress; yet, its effect on neurotransmitter catabolic enzymes has not been elucidated. We investigated the effects of ACR exposure on brain and hepatic tissues antioxidant enzymes activities and different markers such as, acetylcholinesterase (AChE), nitric oxide (NO), monoamine oxidase (MAO), and lipid profile, and to evaluate the protective effects of garlic against ACR toxicity. Male Sprague-Dawley rats were exposed to ACR (1 mg kg^?1 body weight) with or without diet containing 1.5% of garlic powder for 40 days. ACR administration showed a decrease in AChE activity associated with an increase in MAO activity in both brain and hepatic tissues. In addition, ACR administration increased the lipid peroxidation and NO levels of both tissues while decreased the activities of glutathione (GSH), superoxide dismutase, and glutathione-S-transferase (GST). On the other hand, the activities of glutathione peroxidase (GPx) and catalase activities increased as a consequence of GSH depletion after ACR exposure. Finally, ACR exposure increased the brain and liver lipid profile of cholesterol, triglycerides and total lipid, while phospholipids level was decreased. Coadministration of garlic powder with ACR significantly attenuated oxidative stress, MAO activity, and inflammation in brain and hepatic tissues but did not ameliorate AChE activity. In conclusion, our results emphasized the role of garlic as a potential adjuvant therapy to prevent ACR neurotoxicity and hepatotoxicity.     

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.     

Effects of benzo(k)fluoranthene,a polycyclic aromatic hydrocarbon on DNA damage,lipid peroxidation and oxidative stress in marine gastropod Morula granulata

Benzo(k)fluoranthene [B(k)F] is one of the widespread priority pollutants of polycyclic aromatic hydrocarbons that has been scarcely studied for exposure assessment. With studies reporting a high amount B(k)F in sediments and water samples around the world, it has become vital to study its effects on aquatic organisms. In this connection, this study is conducted to study the effect of different concentrations of B(k)F (1, 10, 25 and 50?µg/L) in marine gastropod Morula granulata exposed in vivo for 96?h. A concentration-dependent increase in percentage tail DNA (TDNA) as measured by comet assay was observed in snails exposed to B(k)F. Exposure concentrations above 1?µg/L B(k)F showed significant increase in superoxide dismutase (SOD) activity and lipid peroxidation value in snails. After 96?h, SOD activity was found to be doubled for 50?µg/L B(k)F in comparison to control. A significant increase in catalase and glutathione S-transferase activity was observed at all exposure conditions at the end of the exposure time. Our study showed that B(k)F induces oxidative stress in snails which further lead to genotoxic damage. To our knowledge, this is the first study on oxidative stress and genotoxic damage in gastropods exposed to B(k)F.