Modulation of ethion-induced hepatotoxicity and oxidative stress by vitamin E supplementation in male Wistar rats

Organophosphorus insecticides (OPIs) may induce oxidative stress leading to generation of free radicals and alteration in antioxidant system of animals. Many studies reported that enzymatic and non-enzymatic antioxidant may play protective role against OPIs induced toxicity in human and rats. The aim of present study was to investigate the possible protective role of vitamin E on ethion-induced hepatotoxicity in rats using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups; each group consists of six animals. Animals were treated for a period of 28 days. Group I (control group received corn oil); Group II [ethion treated (2.7 mg/kg bw/day)]; Group III (vitamin E treated (50 mg/kg of bw/day)]; Group IV (ethion + vitamin E treated). Animals were sacrificed after 7, 14, 21 and 28 days by decapitation and liver tissue was used for the measurement of proteins, lipid peroxidation (LPO), reduced glutathione (GSH) content and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST). Erythrocytes were analyzed for acetyl cholinesterase activity. The result of this study shows that in vivo administration of ethion caused a significant induction of oxidative damage in liver tissue as evidenced by increased level of LPO and decreased GSH content. Ethion toxicity also led to a significant increase in the activities of SOD, CAT, GPx and GST in liver tissue. In addition, decrease in GR activity was observed in ethion administered rats compared to control. Histopathological findings revealed that exposure to ethion caused damage in liver tissue. However, simultaneous supplementation with vitamin E restored these parameters partially. In conclusion, the results of the current study revealed that ethion-induced toxicity caused lipid peroxidation, alterations in the antioxidant enzymes and histopathological changes in liver. Supplementation of vitamin E exhibited protective effect by inhibiting ethion-induced toxicity in liver and erythrocytes.     

Nonthiol ACE inhibitors, enalapril and lisinopril are unable to protect mitochondrial toxicity due to paraquat

Angiotensin-converting enzyme inhibitors (ACEi) were shown to ameliorate endothelial dysfunction in various human diseases and some of these inhibitors have been reported to enhance antioxidant defenses. The objective of the present study was to shown the abilities of enalapril and lisinopril as two nonthiol ACEi on mitochondrial toxicity due to paraquat. In this study, mitochondrial isolation from rat liver was divided into six groups. Group 1 was considered as control, group 2 received paraquat (5 mM), group 3 received enalapril (0.25 mM), group 4 received lisinopril (0.01 mM), group 5 received paraquat (5 mM) + enalapril (0.25 mM), and group 6 received paraquat(5 mM) + lisinopril (0.01 mM). Viability, lipid peroxidation, catalase activity, GSH (reduced glutathione) and GSSG (oxidized glutathione) concentrations were also determined. Simultaneous treatment of mitochondria with enalapril (0.25 mM) + paraquat (5 mM) and lisinopril (0.0.01 mM) + paraquat (5 mM) did not significantly ameliorate the mitochondrial toxicity induced by paraquat (5 mM) alone (p > 0.05). However, the nonthiol ACEi, enalapril showed to partially improve target of lipid peroxidation due to paraquat. In conclusion, nonthiol ACEi treatment did not improve the increased oxidative stress and the decreased antioxidant mechanisms.     

The effects of Saw palmetto on flumethrin-induced lipid peroxidation in rats

In the present study, 40 male Wistar albino rats were used and divided into 4 groups. The first group served as the control group; the second group was administered Saw palmetto extract at the dose of 20 mg/kg/bw; the third group was administered flumethrin at the dose of 15 mg/kg/bw; and the fourth group was administered a combination of 20 mg/kg/bw Saw palmetto extract and 15 mg/kg/bw flumethrin, for 21 days, orally. After the trial period, blood and tissue (liver, kidney and brain) samples were taken from the rats. Saw palmetto extract did not cause significant alterations in plasma and tissue malondialdehyde (MDA) levels, serum and tissue nitric oxide (NO) levels, erythrocyte and tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities when compared to the controls (p > 0.05). Flumethrin led to increased plasma and tissue MDA levels, serum and tissue NO levels, tissue GSH-Px activities and decreased erythrocyte and tissue SOD and CAT activities, and erythrocyte GSH-Px activity, compared to the controls (p < 0.05). The flumethrin and Saw palmetto extract combination increased erythrocyte SOD activity and decreased brain GSH-Px activity as compared to flumethrin (p < 0.05). In conclusion, it was determined that Saw palmetto extract did not cause any negative effect on the prooxidant-antioxidant balance. While flumethrin stimulated lipid peroxidation; Saw palmetto extract at the dose of 20 mg/kg/bw did not exhibit enough antioxidant effect in rats.     

Lipid peroxidation and oxidative stress in rat erythrocytes induced by chlorpyrifos and the protective effect of zinc

Male and female rats were orally administered chlorpyrifos at a dose of 6.75 mg kg⁻¹ body weight for 28 consecutive days. An additional chlorpyrifos group received zinc (227 mg l⁻¹) in drinking water throughout the experimental duration. Two groups more served as controls; one received water only and the other received zinc in drinking water. Administration of chlorpyrifos resulted in a significant increase in lipid peroxidation (LPO) level and significant decrease in the activities of superoxide dismutase (SOD), glutathione-s-transferase (GST), catalase (CAT) and acetylcholinesterase (AChE) in erythrocytes of male and female rats. In contrast, zinc-chlorpyrifos treatment showed insignificant differences (p ? 0.05-0.01), compared to control results, regarding LPO, SOD, GST and CAT. In case of AChE, supplementation of zinc showed little alteration in the activity of this enzyme in the rats treated with chlorpyrifos. It can deduce that chlorpyrifos induced oxidative stress and lipid peroxidation in erythrocytes of male and female rats. The overall results reveal the pronounced ameliorating effect of zinc in chlorpyrifos-intoxicated rats and variation in the response of male and female animals regarding alteration in the level of some biochemical parameters and LPO.     

Protective roles of vitamin E (α-tocopherol), selenium and vitamin E plus selenium in organophosphate toxicity in vivo: A comparative study

In the present study, we investigated the possible protective role of vitamin E, selenium (Se) and vitamin E plus Se in fenthion-induced organophosphates (OP) toxicity in rats. Serum concentrations of ascorbic acid, retinol, β-carotene, ceruloplasmin, nitrite and nitrate as well as levels of malondialdehyde (MDA) and reduced glutathion (GSH) in whole blood and in some tissues such as brain, heart, jejunum, kidney, liver, lung, muscle and pancreas were measured in sham, control, vitamin E, Se and vitamin E + Se groups. Compare to the sham group, the MDA (p < 0.001) and GSH (p < 0.01) levels in whole blood and some in tissues were significantly higher in the control animals. Ceruloplasmin levels of the control (p < 0.05), vitamin E (p < 0.05) and vitamin E + Se (p < 0.01), groups were higher than the sham group. Ascorbic acid, retinol, β-carotene as well as nitrite and nitrate levels in the control group were significantly lower than sham, vitamin E, Se and vitamin E + Se groups. We concluded that fenthion toxicity-induced lipid peroxidation and generation of free radicals in whole blood and tissues. Additionally, the antioxidants we tested did show a significant protective effect against OP-induced tissue and blood injury at the biochemical level.     

Effects of N-acetylcysteine on oxidative responses in the liver of fenthion exposed Cyprinus carpio

The aim of this study was to evaluate the effects of different N-acetylcysteine doses on the tolerance to fenthion-induced oxidative stress, alterations in glutathione metabolism and cholinesterase specific activities in the liver by using freshwater fish Cyprinus carpio (Cyprinidae) as a model organism. An acute toxicity study was carried out to determine 96-h median lethal concentration of fenthion for this species (2.16 mg/L) and 80% of this concentration was applied in toxicity studies. Four groups, each containing eight fish were constituted as follows: Control group, fenthion treated group, 0.5 or 400 mg/kg NAC-injected + fenthion-treated groups. Biochemical analyses were carried out spectrophotometrically. Fenthion treatment significantly decreased total glutathione and glutathione levels, glutathione/glutathione disulfide ratio together with glutathione reductase and γ-glutamylcysteine synthetase specific enzyme activities. The higher dose of N-acetylcysteine increased the toxic effects of fenthion and γ-glutamyl transpeptidase specific activity while decreasing glutathione S-transferase specific activity. However, injection of the lower dose provided a limited protection against fenthion toxicity. In all exposure groups, lipid peroxidation increased and total protein levels decreased, while protein depletion was prevented by low dose of N-acetylcysteine application. Acetylcholinesterase and butyrylcholinesterase activities were at similar levels in the liver of C. carpio. A dose-dependent inhibition was observed in butyrylcholinesterase activity by N-acetylcysteine application. The results showed that fenthion had a significant oxidative stress inducing potential through the reduction of glutathione redox capacity. The critical point for overcoming oxidative stress by N-acetylcysteine in fenthion toxicity was the selection of the dose; N-acetylcysteine exerted its toxic effects by means of oxidative stress in fish liver at the higher dose.     

Oxidative stress, steroid hormone concentrations and acetylcholinesterase activity in Oreochromis niloticus exposed to chlorpyrifos

We investigated the endocrine disrupting effects of chlorpyrifos-ethyl which is suspected to be originated from oxidative stress. Initially, the 96 h LC₅₀ values of chlorpyrifos in juvenile and adult of Oreochromis niloticus were determined to be 98.67 μg/L and 154.01 μg/L, respectively. Sub-lethal concentrations of chlorpyrifos-ethyl (5 ppb, 10 ppb, 15 ppb) were administrated to adult fish for 15 and 30 days. Fish were then left to depurate for 15 days in pesticide-free water. Gonadal somatic indices, serum sex steroids as indicators of reproductive function and cortisol level as indicator of stress condition were measured to observe the endocrine disruption effects of chlorpyrifos-ethyl. Gonadal glutathione S-transferase and antioxidant enzyme activities and lipid peroxidation as indicators of oxidative stress were also measured. Acetylcholinesterase activity was measured as a marker of chlorpyrifos toxicity. Results showed that serum estradiol, testosteron and cortisol levels in fish exposed to chlorpyrifos were lower than those of the control fish while gonad somatic indices did not change during the experiments. After 30 days, chlorpyrifos exposure decreased GST activity, and increased SOD enzyme activity by up to 215-446% compared with the control, suggesting there was a oxidative stress. No statistically significant differences between GPx and CAT specific activities, protein contents and lipid peroxidation were determined between control and treatment groups in all exposure concentrations and periods. Acetylcholinesterase activity decreased (45.83-77.28%) in gonad tissues. After recovery serum estradiol and testosteron levels were similar to those of the control levels. An increase in the GST and SOD enzyme activities were determined. Cortisol level and AChE activity in all exposure groups decreased after the depuration period, and fish were unable to overcome the stress of chlorpyrifos. Thus, this study revealed that after chlorpyrifos treatments there exists a protective function of antioxidant enzymes against lipid peroxidation in gonad tissue of O. niloticus. There also exist lower testosteron and estradiol levels in exposed fish than those of the control fish without any alterations in oxidative stress, which is attributed to the capability of chlorpyrifos to impair steroid hormone levels.     

Caffeic acid phenethyl ester and vitamin E moderates IL-1β and IL-6 in bleomycin-induced pulmonary fibrosis in rats

The aim of this study was to investigate the effects of Caffeic acid phenethyl ester (CAPE), which has been demonstrated to have antiinflammatory, antiproliferative, anticancerogenic, and antioxidant effects, and vitamin E on IL-1β and IL-6 in bleomycin-induced (BLM-induced) pulmonary fibrosis in rats. Thirty-two Sprague-Dawley rats were divided randomly into four groups as untreated control, bleomycin, bleomycin + CAPE, and bleomycin + vitamin E groups. At the end of the treatment, blood IL-1β and IL-6 levels were quantified. Bleomycin application to the rats resulted in a significant increase in the cytokine levels as compared to the controls. Administration of CAPE and vitamin E prevented the increase of blood IL-1β and IL-6 levels compared to the rats treated with bleomycin alone. Data presented here suggest that CAPE and vitamin E play a protective and moderator role against BLM-induced lung injuries by decreasing the primary inflammatory cytokines, such as IL-1β and IL-6.     

Effects of thiacloprid, deltamethrin and their combination on oxidative stress in lymphoid organs, polymorphonuclear leukocytes and plasma of rats

Deltamethrin and thiachloprid are an α-cyano class pyrethroid and neonicotinoid insecticide, respectively. Recently, a pesticide combining deltamethrin and thiacloprid has also been released. In the present study, the acute and subacute toxic effects of deltamethrin, thiachlopride, and a combination of these insecticides, on the lymphoid organs (spleen, thymus and bone marrow), polymorphonuclear leukocytes (PMNs) and plasma of rats, were determined to better understand mammalian antioxidant-oxidant and inflammatory system responses. For this purpose, rats were treated orally with different doses of thiacloprid (single acute dose of 112.5 mg/kg); subacute dose of 22.5 mg/kg/day for 30 days; deltamethrin (single acute dose of 15 mg/kg); subacute dose (3 mg/kg/day for 30 days), or a combination of these pesticides. Results were compared with those from a comparable dosing regimen with the known immunosuppressive drug cyclophosphamide. Pesticide treatments caused significant changes in the levels of liver and kidney injury markers. Antioxidant enzyme (catalase and glutathione peroxidase), glutathione and plasma antioxidant levels decreased but lipid peroxidation increased in all lymphoid organs and the plasma. Glutathione-S-transferase and especially DT-diaphorase activity, decreased after thiacloprid treatment. Myeloperoxidase activity, carbonyl content, lipid peroxidation and total nitrite levels increased in PMNs and plasma. When evaluated as a whole, the oxidative and inflammatory stresses seen in the pesticide combination groups were not much more pronounced than in the groups treated with a single pesticide. In terms of the evaluated biochemical parameters, the pesticides showed similar effects to cyclophosphamide.     

Effects of diazinon on biochemical parameters of blood in rainbow trout (Oncorhynchus mykiss)

Existence of diazinon, an organophosphorous pesticide, in river waters of Iran near rice paddy fields has been reported by some authors. The present research aimed to determine the acute toxicity and evaluate the effect of sub-lethal concentrations of diazinon on some biochemical parameters of rainbow trout, Oncorhynchus mykiss after 7, 14 and 28 days. No significant differences were observed in the plasma levels of creatinine among the treatment groups at different sampling intervals. Acetylcholinesterase activity and the levels of total protein, albumin as well as globulin in plasma were significantly reduced at both concentrations tested (p < 0.05). Lactate dehydrogenase activity was only decreased on 7th day in 0.1 mg/L diazinon treatment (p < 0.05). Creatine kinase activity was significantly lower in 0.1 mg/L diazinon group at 14th and 28th sampling periods, whereas its activity significantly increased in fishes exposed to 0.2 mf/L diazinon only on 7th day (p < 0.05). Aspartate aminotransferase, alanine aminotransferase activities and glucose levels in diazinon treated groups were significantly higher than the controlled group at experimental periods (p < 0.05). In conclusion, long-term exposure to diazinon at sub-lethal concentrations induced biochemical alterations in rainbow trout, and offers a simply tool to evaluate toxicity-derived alterations.     

Effect of ginger supplementation on developmental toxicity induced by fenitrothion insecticide and/or lead in albino rats

Evaluation of the antioxidant and antiteratogenic role of ginger Zingiber officinale polyphenols against the toxicity induced by fenitrothion and/or lead in female albino rats were investigated. Adult virgin females were divided into 8 groups and were orally treated as follow: control (C), 1% w/w of ginger (G), 120 μg/animal lead as lead acetate (L), 10 mg/kg of fenitrothion (F), lead (120 μg/animal) fenitrothion (10 mg/kg) (LF), ginger (1%w/w) + fenitrothion (10 mg/kg) (GF), ginger (1%w/w) + lead (120 μg/animal) (GL), ginger (1%w/w) + lead (120 μg/animal) + fenitrothion (10 mg/kg) (GLF). Treatments were expanded for 28 days before pregnancy and during gestation period from zero to 6th day. Blood samples were taken at the day 20th of gestation and animals were sacrificed to investigate the effect of tested substances on dams and development of their fetuses. Inhibition in AchE in (F) and (LF) groups and elevation in plasma AchE in (L) groups were observed. Elevation in oxidative stress biomarker malondialdehyde (MDA) was recorded in all intoxicated groups concomitants with reduction in total reduced glutathione (GSH) and reduction in the activity of glutathione S-transferase (GST). Elevation in liver function biomarkers alanin amintransferase (ALT) and aspartate aminotransferase (AST) and reduction in plasma total protein and albumin were recorded in (F), (L) and (LF). Supplementation with ginger in diet attenuates the alteration in MDA, GSH, GST, ALT and AST, however, it failed to counteract the effect of F, L and LF on AchE, total protein and albumin. Significant alterations in maternal toxicity were recorded in (GF, GL, LF and GLF) compared with control group. Also, parameters of embryotoxicity and fetotoxicity indicated significant decrease in litter number that observed in F and L and the number of dead fetus/dam and litters number increased in L group. Supplementation with ginger decreased each of the number of died fetus, growth retardation and fetal length, while, it increased fetal weight. As regards to, teratological aspects, the percentage of skeletal malformations and visceral anomalies were observed in all feti obtained from treated groups with different percentages. Supplementation with ginger slightly attenuates the developmental toxicity of fenitrothion and/or lead.     

Changes in selected immunological parameters and antioxidant status of rainbow trout exposed to malachite green (Oncorhynchus mykiss, Walbaum, 1792)

In this study, the effects of malachite green on selected immunological parameters, oxidative stress and antioxidant status biomarkers in blood, liver, kidney, spleen and gill of rainbow trout, Oncorhynchus mykiss, was examined. During 5 days the malachite green was applied at concentrations of 1/15,000 and 1/150,000 for 30 s and 60 min, respectively. Immunological parameters (nitroblue tetrazolium (NBT) activity, total plasma protein (TP), total immunoglobulin (TI)) and biochemical parameters (lipid peroxidation (MDA), catalase (CAT) activity, reduced glutathione (GSH) levels) were evaluated after exposed to malachite green. It has been observed that NBT activity (p < 0.05, p < 0.001), total protein (p < 0.01, p < 0.001) and total immunoglobulin (p < 0.05, p < 0.001) levels were decreased compared with control group. In the rainbow tout exposed to malachite green duration 5 days significantly increased lipid peroxidation, which might be associated to decreased levels of reduced glutathione and catalase activity in the whole tissues of O. mykiss (p < 0.05, p < 0.01, p < 0.001 for each cases).     

Effect of α tocopherol and selenium on antioxidant status, lipid peroxidation and hepatopathy induced by malathion in chicks

The objective of the present study was to investigate the role of α tocopherol and selenium on malathion induced hepatic damage, and antioxidant defense in chicks. The chicks were divided into three groups. First group received malathion 10 mg/kg BW, orally for 60 days, the second group received the same dose of malathion but was supplemented with α tocopherol and selenium for 60 days and the third group served as the control. A compromised antioxidant capacity as evidenced by increased levels of erythrocytic lipid peroxidation and decreased concentration of vitamin E and decreased activity of glutathione peroxidase was observed in chicks following the administration of malathion. An improved antioxidant status was observed in chicks of second group with α tocopherol and selenium supplementation including higher concentration of vitamin E, increased activity of glutathione peroxidase and lower levels of lipid peroxidation. Histopathological studies of liver in the chicks which received malathion exhibited, moderate to severe degenerative and necrotic changes in the hepatocytes. The correlation of decreased antioxidant status of chicks with degenerative changes in liver suggests that lipid peroxidation may be one of the important mechanism in the chronic toxicity of malathion. The results indicate that α tocopherol and selenium were effective in partially alleviating degenerative changes induced by malathion in the liver of chicks by attenuating processes leading to lipid peroxidation.     

Protective effects of Nigella sativa oil on propoxur-induced toxicity and oxidative stress in rat brain regions

Propoxur (PPr) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Because of the widespread use of pesticides for domestic and industrial applications, evaluation of their neurotoxic effects is of major concern to public health. The aim of the present study was to evaluate the possible protective effects of Nigella sativa oil (NSO), an antioxidant agent, against PPr-induced toxicity and oxidative stress in different brain regions of rats including cerebellum, cortex and hippocampus. In the present study, 32 male Sprague-Dawley rats were used and divided into four equal groups. Group 1 was allocated as the control group. Groups 2-4 were orally administered 1 ml/kg/bw/day NSO, 8.51 mg/kg/bw/day PPr or NSO plus PPr, respectively, for 30 days. Lipid peroxidation (LPO), protein carbonyl content (PCC) and acetylcholine esterase activity (AChE) were determined. Enzymatic antioxidant activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST)] and non-enzymatic antioxidants [reduced glutathione (GSH)] were determined. PPr treatment significantly increased the levels of LPO, PCC and oxidized glutathione (GSSG) in brain regions. On the contrary, levels of GSH and the activities of SOD, CAT, GSH-Px, GST and AChE were significantly decreased. NSO treatment to PPr intoxicated rats restored such biochemical parameters to within control levels except GST activity, emphasizing its antioxidant role. We conclude that NSO significantly reduces PPr-induced toxicity and oxidative stress in rat brain regions via a free radicals scavenging mechanism.     

A two generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate after gestational and lactational exposure in female Wistar rats

Polychlorinated biphenyls and diethyl phthalate are both lipophilic in nature and are likely to be present in the same environmental compartment or bioaccumalate over a period of time, thus a mixture toxicity study was undertaken to evaluate the type of interaction between polychlorinated biphenyls (Clophen A60) and diethyl phthalate over two generations in female Wistar rats. Healthy male and female albino rats of Wistar strain weighing 75-100 g (6-7 weeks old) were randomly assigned to four groups of six each. Group I male and female rats were fed on normal diet and water ad libitum. Group II male and female rats were maintained on normal diet mixed with corn oil as oil control. GroupS III and IV male and female rats were given Clophen A60 and diethyl phthalate dissolved in corn oil mixed with the diet at 50 mg/kg of the diet individually to each group. Group V male and female rats received a mixture of diethyl phthalate and Clophen A60, each dissolved in corn oil mixed with the diet at 50 mg/kg of the diet. Hundred days after the treatment, females were mated with the males in each group for 10 days. Exposure to diethyl phthalate and Clophen A60 was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of the parental generation female rats. Treatment for F1 generation male and female pups (6 males & 6 females) with Clophen A60 and diethyl phthalate individually and in mixture was continued at doses reduced to 25 mg/kg of the diet after they reached 75-100 g in weight. The treatment was carried out similar to the parental generation for a period of 150 days. Liver and serum aspartate aminotransferase, liver cholesterol and glycogen were significantly increased in the F1 generation Clophen A60 + diethyl phthalate treated group, whereas serum cholesterol, liver glutathione and glutathione reductase showed a significant decrease in the F1 generation Clophen A60 + diethyl phthalate treated group as compared to the parental generation mixture and individually treated groups as well as the individually treated F1 generation groups. A significant increase was observed in the liver and serum aspartate aminotransferase activity of Clophen A60 and serum aspartate aminotransferase levels of diethyl phthalate treated F1 generation rats as compared to the parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Liver glutathione levels were significantly decreased in the F1 generation Clophen A60 and diethyl phthalate individually treated rats which was similar to the parental generation individually treated rats as compared to the controls. Liver glutathione reductase level was also significantly declined in the diethyl phthalate treated F1 individual group as compared to diethyl phthalate individually treated parental generation rats. Histology of the liver showed fatty degeneration in the mixture treated F1 generation rats as compared to Clophen A60 and diethyl phthalate individually treated F1 rats and parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Thus, in spite of dose reduction and continuous exposure over two generation’s to a mixture of diethyl phthalate and Clophen A60 exposed through gestation, lactation and diet leads to a synergistic toxic effect in the F1 generation.     

Determination of toxicity of trichloroacetic acid in rats: 50 days drinking water study

This study aims to investigate the effects of the trichloroacetic acid (TCA) on serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation content (Malondialdehyde, MDA) in various tissues of rats. TCA (2000 ppm) as drinking water was administered orally to rats (Sprague-Dawley albino) ad libitum for 50 days continuously. TCA treatments caused different effects on the serum marker enzymes, antioxidant defense systems and the MDA content in experimented rats compared to controls. Results showed that TCA caused a significant increase in serum AST, ALT, CPK and ACP activity. The lipid peroxidation end product MDA slightly increased in the erythrocytes, liver and kidney of rats treated with TCA, whereas did not change in the brain. In addition, antioxidant enzyme activity such as CAT and SOD significantly increased in the brain, liver and kidney tissues of TCA induced group whereas the ancillary enzyme GR and the drug metabolizing enzyme GST activity did not significantly change in the all tissues. The observations presented led us to conclude that the administration of subchronic TCA promotes lipid peroxidation content, elevates tissue damage serum marker enzymes and fluctuates in the antioxidative systems in rats. Also the rats resisted to oxidative stress via antioxidant mechanism but the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat’s tissues. These data, along with the determined changes suggest that TCA produced substantial systemic organ toxicity in the erythrocyte, liver, brain and kidney during the period of a 50-day subchronic exposure.     

Endosulfan-induced neurotoxicity and serum acetylcholinesterase inhibition in rabbits: The protective effect of Vit C

The neurotoxic effects and acetylcholinesterase inhibition induced by endosulfan, and the amelioration of these effects by Vitamin C (Vit C), were studied in the brains of New Zealand white rabbits. The cerebrum and cerebellum of each rabbit was examined grossly and histopathologically, and caspase-3 activity was determined by immunohistochemical methods. Twenty-four rabbits were divided into four groups (n = 6). Rabbits in Group I (END) were given a sublethal dose of endosulfan (1 mg/kg bw) in corn oil daily by oral gavage for 6 weeks. Group II (END + C) received the same dose of endosulfan and also Vit C (20 mg/kg bw) every second day during the 6 week period. Group III (OIL + C) received oral corn oil daily and Vit C every second day for 6 weeks. Group IV (OIL) received corn oil daily by oral gavage throughout the experiment. A significant reduction in acetylcholinesterase activity was observed in the END group, which was ameliorated in the END + C group. Hyperemia and slight hemorrhages in brains and cerebellums were seen in some rabbits in the END group. There were no gross cerebral or cerebellar lesions in the other groups. Hemorrhages, degenerations and slight gliosis were the marked histopathological findings of some rabbits belonging to the END group. A positive caspase-3 reaction was more severe in the END group than in the others. An ameliorating effect of Vit C on gross, histopathological, and immunohistochemical findings was observed in the END + C group. Thus, although endosulfan could cause neurotoxic effects in rabbits, this toxicity was decreased by Vit C treatment, which increased serum acetylcholinesterase activity.     

Nephrotoxicity in rats induced by organophosphate insecticide methidathion and ameliorating effects of vitamins E and C

The effects of organophosphate insecticide methidathion (MD) on kidney tissue and the ameliorating effects of a combination of vitamins E and C against subchronic MD toxicity were evaluated in rats. Experimental groups were: control group (group I), 5 mg/kg body weight MD-treated group (group II), and 5 mg/kg body weight MD plus vitamin E plus vitamin C treated group (group III). The groups II and III were treated orally with MD on five days a week for four weeks. Vitamins E and C were injected at doses of 50 mg/kg body weight, i.m. and 20 mg/kg body weight, i.p., respectively, 30 min after the treatment of MD in the group III. Rats were anaesthesized and venous blood samples were collected by direct right ventricle heart puncture, in addition, the right kidney was removed for histopathological examinations and malondialdehyde (MDA) analyses after four weeks. The serum activity of cholinesterase (ChE) and the kidney level of malondialdehyde, and kidney histopathology were studied in rats. MD caused decreased ChE activity (group I: 2114 ± 63 U/L, group II: 1455 ± 100 U/L) and increased MDA level (group I: 147 ± 20.2 nmol/mg protein, group II: 236 ± 25.6 nmol/mg protein), and kidney damage in rats. Furthermore, a combination of vitamins E and C restored partially (ChE activity: 1670 ± 111 U/L, MDA level: 159 19.4 nmol/mg protein) this changes in MD-treated rats.