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.     

Methyl parathion induced nephrotoxicity in male rats and protective role of vitamins C and E

Methyl parathion is an organophosphate insecticide that has been used in agriculture and domestic for several years. Vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day), methyl parathion (0.28 mg/kg bw per day) and vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day) + methyl parathion (0.28 mg/kg bw per day) combination were given to rats orally via gavage for 7 weeks. Body and kidney weights, malondialdehyde (MDA) levels and histopathological changes were investigated at the end of 4th and 7th weeks comparatively with control group. When methyl parathion-treated group and vitamins C and E + methyl parathion-treated group were compared to control group body and kidney weights decreased significantly at the end of 4th and 7th weeks. MDA levels increased in kidney tissues of the methyl parathion- and vitamins C and E + methyl parathion-treated groups compared to control group. MDA levels decreased significantly in vitamins C and E + methyl parathion treated group compared with methyl parathion treated group at the end of 4th and 7th weeks. In our light microscopic investigations, after 4 weeks of methyl parathion exposure, glomerular atrophy and vascular dilatation, and after 7 weeks, necrosis and edema were observed in the kidney tissues. After 4 weeks of vitamins C and E + methyl parathion exposure, mononuclear cell infiltrations, and after 7 weeks, calcification were detected in the kidney tissues.     

Acute, subacute and subchronic administration of methyl parathion-induced testicular damage in male rats and protective role of vitamins C and E

Methyl parathion is an organophosphate insecticide that has been used in agriculture and domestic for several years. Vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day), methyl parathion (0.28 mg/kg bw per day) and vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day) + methyl parathion (0.28 mg/kg bw per day) combination were given to rats orally via gavage for 7 weeks. Body and testis weights, sperm counts, sperm motility, sperm morphology and histopathological changes in the testes were investigated at the end of 24 h, 4th and 7th weeks comparatively with control group. No pathological changes were observed in all parameters at the end of 24 h. When methyl parathion-treated group and vitamins C and E + methyl parathion-treated group were compared to control group, body and testis weights decreased significantly at the end of 4th and 7th weeks. It was observed that, at the end of 4th and 7th weeks there was a statistically significant decrease in sperm counts and sperm motility, increase in abnormal sperm morphology when methyl parathion- and vitamins C and E + methyl parathion-treated group were compared to control group. While sperm counts increased at the end of 4th and 7th weeks, sperm motility increased at the end of 7th week when vitamins C and E + methyl parathion-treated group compared with methyl parathion-treated group, no changes were observed in abnormal sperm morphology at the end of 4th and 7th weeks. In our light microscopic investigations, after 4 and 7 weeks of methyl parathion exposure, necrosis and edema were observed in the seminiferous tubules and interstitial tissues. After 4 and 7 weeks of vitamins C and E + methyl parathion exposure, degenerative changes were detected in the seminiferous tubules while no pathological findings were observed in the interstitial tissues. According to the present study, we conclude that vitamins C and E reduces methyl parathion testicular toxicity, but it does not protect completely.     

The effects of diazinon on pancreatic damage and ameliorating role of vitamin E and vitamin C

The aim of this study was to investigate effects of an organophosphate insecticide, diazinon (DI), on pancreas, and possible ameliorating role of vitamins E and C. We examined both in vivo and in vitro effects of DI on serum activities of alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), amylase, and lipase enzymes. We also evaluated possible ameliorating effects of vitamins E and C combination against DI toxicity and blood levels of thiobarbituric acid reactive substances (TBARS) only in vivo. In vivo experimental groups were: control group, DI-treated group, and DI + vitamins E plus C-treated group. In vitro study groups were: control group and DI-treated group. The biochemical analyses were determined in in vitro experiments at both hour 0 and 24 while in in vivo experiments were determined only at hour 24. Lipase activity and TBARS level were found increased by DI in in vivo experiments while lipase activity was found decreased in in vitro experiments. Amylase and ALP activities were found decreased by DI in both in vivo and in vitro experiments. Also, the combination of vitamins E and C was found to partially improve these disorders. These results suggest that DI treatment causes pancreas damage via increasing oxidative stress in rats, and a combination vitamins E and C can reduce this lipoperoxidative effect.     

Chlorpyrifos-induced oxidative stress and histological changes in retinas and kidney in rats: Protective role of ascorbic acid and alpha tocopherol

This study was undertaken to evaluate the antioxidant effect of vitamins C and E against oxidative stress, apoptosis and histological changes of kidney and retina in CPF-treated rats. Forty male Sprague-Dawley rats were divided into four groups including the control group, the group treated orally with a single dose of CPF (63 mg/kg b.w.), the group injected intramuscularly (i.m.) with vitamin C (250 mg/kg b.w.), and intraperitonealy (i.p.) with vitamin E (150 mg/kg b.w.) daily for 7 days and the group treated with CPF (single dose) and injected with vitamins (for 7 days). The results showed that CPF induced apoptosis and severe oxidative stress as indicated by the significant increase in MDA and sFasL concentration and the significant decrease in GSH concentration in serum. Co-administration of vitamins C and E ameliorate these toxic effects and improved the histological pictures of kidneys and retinas. It could be concluded that combined administration of vitamins C and E is useful in the routine therapy for the protection against tissue damage induced by CPF.     

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.     

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.     

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.     

The effects of organophosphate insecticide diazinon on malondialdehyde levels and myocardial cells in rat heart tissue and protective role of vitamin E

Diazinon is an organophosphate insecticide has been used in agriculture and domestic for several years. Vitamin E (200 mg/kg, twice a week), diazinon (10 mg/kg, per day), and vitamin E (200 mg/kg, twice a week)+diazinon (10 mg/kg, per day) combination was given to rats orally via gavage for 7 weeks. Body and heart weights, malondialdehyde (MDA) level in heart tissue and ultrastructural changes in myocardial cells were investigated at the end of the 1st, 4th, and 7th weeks comparatively with control group. When diazinon-treated group was compared to control group body and heart weights were decreased significantly at the end of the 4th and 7th weeks. It was observed that, at the end of 1st, 4th, and 7th weeks there was a statistically significant increase in MDA levels when diazinon- and vitamin E +diazinon-treated groups were compared to control group. While at the end of the 1st week statistically significant changes were not being observed, at the end of 4th and 7th weeks statistically significant decrease was detected in MDA levels when vitamin E+diazinon-treated group was compared to diazinon-treated group. In our electron microscopic investigations, while vacuolization and swelling of mitochondria myocardial cells of diazinon-treated rats were being observed, swelling of several mitochondria were observed in vitamin E+diazinon-treated rats. We conclude that vitamin E reduces diazinon cardiotoxicity, but vitamin E does not protect completely.     

Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of organophosphate insecticides (OPIs), the aim of this study was to investigate the ameliorative properties of vitamin E (vitE) against the subchronic effect of diazinon (DZN) on oxidative damage markers such as lipid peroxidation (LPO) and the antioxidant defense system (ADS) in the liver of male MFI albino mice. The groups were intraperitoneally (i.p) administered with either vehicle or vitE (100 mg/kg body weight) or ¼ LD₅₀ of DZN (16.25 mg/kg b.w.) or ½ LD₅₀ of DZN; 32.5 mg/kg b.w) or ¼ LD₅₀-DZN + vitE or ½ LD₅₀ + vitE every consecutive day for 14 days. Hepatic damage markers analysis revealed that alanine transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly decreased in both DZN doses. Also, the significantly increased levels of biomarkers of oxidative stress as LPO and protein carbonyl (PC) and the decreased antioxidant defenses like reduced glutathione (GSH), and free radical scavenger enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx) were noted in DZN-treated groups as compared to control group. Distinctly lower levels of GSH and increased levels of LPO, along with alterations in endogenous antioxidant enzymes were evident in hepatic toxicity of DZN which is dose-dependent. Hepatic specific marker enzymes were restored to normalcy in mice supplemented with vitE following treatment with DZN which otherwise was decreased in the DZN-treated mice. The results show that co-treatment of vitE with DZN prevents or diminishes the oxidative stress of DZN-treated mice and may act as a putative protective agent against DZN-induced liver tissue injury.     

Stimulation of insulin and glucagon synthesis in rat Langerhans islets by malathion in vitro: Evidence for mitochondrial interaction and involvement of subcellular non-cholinergic mechanisms

We examined the effects of malathion, an organophosphorus (OP) insecticide, on glucagon, C-peptide, and insulin content or secretion from isolated rat Langerhans islets in vitro. Islets were isolated from the pancreas of rats by standard collagenase digestion, separation by centrifugation, and hand-picking technique. Then islets were cultured in medium and supplemented with various concentrations of malathion (25, 125, and 625 μg/ml) for 1, 3, and 5 h. In vitro exposure to malathion increased insulin and C-peptide contents at doses of 25, 125, and 625 μg/ml following 5 h incubation as compared to control. All doses of malathion increased glucagon content after 3 and 5 h as compared to control. Increase of the glucagon content at all doses in the fifth hour was higher than that of third hour. Malathion also decreased 2.8 and 16.7 mM glucose-stimulated insulin secretion at all doses after 30 min as compared to control.It is concluded that malathion reduce insulin exocytose in a short time (first hour) but after a long time (e.g., 5 h), the content of insulin is increased by compensating mechanisms such as resynthesize of insulin or aggregation of insulin. The present in vitro study for the first time proposes the involvement of subcellular non-cholinergic mechanisms in malathion-induced changes in Langerhans islets insulin and glucagon.     

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.     

Evaluation of aspect of some oxidative stress parameters using vitamin E, proanthocyanidin and N-acetylcysteine against exposure to cyfluthrin in mice

A hundred and sixty female white mice, each weighing 35-40 g, were used in this study. The animals were assigned into eight groups as one control group and 7 experimental groups. Groups 2, 3 and 4 were administered N-acetylcysteine (NAC), proanthocyanidin and vitamin E alone, at doses of 100 mg/kg/body weight/day by intra-peritoneal, oral route and, intramuscular, respectively. Group 5 was administered a single dose of cyfluthrin (100 mg g/kg/body weight ∼1/3LD₅₀) by oral, whereas Groups 6, 7 and 8 were given cyfluthrin+NAC, cyfluthrin+proanthocyanidin and cyfluthrin+vitamin E, at the same dose, respectively. The administration of the drugs was initiated following the administration of cyfluthrin, and continued until the end of the seventh day of the study. Blood samples were collected from each group, 24 h, and 3, 7 and 9 days after the administration of cyfluthrin for the assessment of blood malondialdehyde (MDA) levels and superoxide dismutase (SOD) and catalase (CAT) activities. According to the data obtained, compared to the control group, increase in the plasma MDA level of the group administered cyfluthrin alone, and decrease in erythrocyte SOD activities in some periods and CAT activities in all periods were determined. On the other hand, especially, MDA levels and CAT activities were observed to move closer to values of the control group, in the groups that were administered NAC, proanthocyanidin and vitamin E in addition to cyfluthrin. In other words, in most periods, decrease in plasma MDA levels, and increase in erythrocyte CAT and SOD activities were observed in comparison to the group administered cyfluthrin alone. Statistical analyses demonstrated significant differences to exist between the groups on the third, seventh and ninth days with respect to plasma MDA levels, and the third and ninth days with respect to erythrocyte SOD and CAT activities (P < 0.05). However no significant difference was demonstrated in any of the periods in the groups that were administered NAC, proanthocyanidin and vitamin E alone in comparison to the control group (P > 0.05). In view of the parameters examined, animals were concluded to be affected by cyfluthrin and the administration of the three compounds at the indicated doses and for the indicated periods were considered to alleviate the adverse effects of cyfluthrin partly throughout the study period.     

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.     

Induction of insulin resistance by malathion: Evidence for disrupted islets cells metabolism and mitochondrial dysfunction

Hyperglycemia is observed with exposure to organophosphorus (OP) pesticides. The aim of this study was to investigate the effects of malathion on secretion of insulin from rat pancreatic islets in vitro and in vivo. Malathion was administered through food for 4 weeks at concentrations of 100, 200, and 400 ppm. For in vivo experiment, at the end of treatment, blood sample was obtained and plasma was separated. For in vitro experiment, the treated rats were anesthetized and underwent a laparatomy. The common bile duct was cannulated and the pancreas distended by injecting of cold collagenase V using peristaltic infusion pump. Islets were then hand picked under a stereomicroscope and cultured in the presence of various doses of glucose and KCl. Malathion at doses of 200 and 400 ppm increased plasma glucose and insulin concentrations and lowered activity of erythrocyte acetylcholinesterase. The isolated islets from pretreated animals with malathion 200 and 400 ppm showed lower glucose-stimulated insulin secretion while no change was observed in the presence of KCl. Light microscopic examination revealed that malathion causes patchy degenerative changes in pancreatic islets. Combination of in vivo and in vitro findings suggests that malathion induces a kind of insulin resistance that cannot overwhelm hyperglycemia. This action of malathion is mediated through disruption of islets mitochondrial function.     

Dimethoate induced biochemical perturbations in rat pancreas and its attenuation by cashew nut skin extract

The significant antiradical activity of cashew skin extract was previously described. In this investigation, the extent of protection offered by cashew nut skin extract (CSE) against the damage induced in rat pancreas by sub chronic doses dimethoate (DM), an organophosphorous pesticide was studied. Rats were supplemented with CSE at 20 mg/kg b.w./d after a daily dose of DM at 40 mg/kg/d b.w. for 2 months. Weekly random blood glucose, oral glucose tolerance test (OGTT); pancreatic damage markers like amylase and lipase; oxidative damage markers such as reactive oxygen species generated, extent of lipid peroxidation, host antioxidant defenses like reduced glutathione (GSH); GSH-dependent enzyme activities viz., glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR); free radical scavenger enzymes viz., catalase and superoxide dismutase (SOD); xenobiotic metabolizing enzymes like DT-diaphorase and NADPH-diaphorase were measured in the four different groups namely (1) control, (2) DM treated, (3) CSE supplemented, (4) CSE supplements following DM treatment. Random blood glucose levels increased significantly on exposure to DM compared to that in control rats (119 ± 5 mg/dl vs. 92 ± 4 mg/dl), while the blood glucose levels in CSE supplemented rats were comparable to that of controls. DM treated rats exhibited impaired glucose tolerance at the end of two months as indicated by OGTT, while DM treated rats with CSE supplements showed normal glucose tolerance. Pancreatic specific marker enzymes like amylase and lipase in serum were restored to normalcy in rats supplemented with CSE following treatment with DM which otherwise was increased in the DM treated rats. Distinctly lower levels of GSH, increased levels of ROS, higher extent of lipid peroxidation, along with alterations in antioxidant enzymes and increase in xenobiotic metabolizing enzymes were evident in pancreas of DM treated rats. However, CSE supplement ameliorated the biochemical alterations in the pancreatic milieu in DM treated rats. Treatment with CSE significantly protected rat pancreas from injury, thus ameliorating and restoring tissue antioxidant status and also conferring normal glucose tolerance. The active components present in cashew skin extract can perhaps be effective in reducing the extent of pancreatic injury and in overcoming tissue damage caused by exposure to dimethoate.     

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.     

Effects of diazinon at different doses on rat liver and pancreas tissues

Diazinon is one of the most widely used organophosphates in agriculture. Toxic effects of diazinon are due to the inhibition of acetylcholinesterase, an enzyme needed for proper nervous system function. This study was designed to investigate the effects of diazinon at different doses on pancreas and liver tissues and in which dose level diazinon shows its effects. Sixty male Wistar albino rats were included in this study. Animals were initially divided into control and diazinon given groups. There were 10 animals in the control group and 50 animals in diazinon administered group. The latter was divided into five equal subgroups: 25, 50, 100, 200 and 300 mg/kg of diazinon administered groups. Control group was given only saline. All animals in 300 mg/kg diazinon group died. After 24 h, rats were sacrificed under ether anesthesia. Tissue and blood samples were taken for biochemical and histopathological analysis. Sample tissues were examined under light microscope. In biochemical analysis, AST, ALT, LDH, amylase and lipase enzyme activities were measured. One-way ANOVA test was used to compare the groups. In 200 mg/kg diazinon given group, it has been observed some histopathological changes in pancreas and liver tissues. Cholinesterase activities were significantly decreased and alkaline phosphatase levels were increased in all diazinon given groups, when compared with the controls. There was statistically significant difference between the control and diazinon given groups by means of serum amylase, lipase, ALT and AST activities (p < 0.05). LDH activities were significantly increased in 100 and 200 mg diazinon given groups, when compared with the controls (p < 0.05). Histopathological changes were observed only in 200 mg diazinon given group. This evidence suggest that diazinon effect is dose dependent and this is possibly 10-15% of the LD₅₀ dose (200 mg/kg), which cause acute pancreatitis and histopathological changes in liver.     

Effects of trichlorfon and sodium dodecyl sulphate on antioxidant defense system and acetylcholinesterase of Tilapia nilotica in vitro

The effects of organophosphorus insecticide trichlorfon, surfactant sodium dodecyl sulphate (SDS), and the mixture of trichlorfon and SDS on the antioxidant defense system and acetylcholinesterase (AChE) in Tilapia nilotica were assessed in vitro. Various concentrations of trichlorfon (0, 0.0001, 0.001, 0.01, 0.1 and 1 g/L) and SDS (0, 0.0625, 0.125, 0.25, 0.5, 1 g/L) were incubated with homogenate of liver and muscle, respectively, at 25 °C for 0, 30, 60 and 90 min. Two concentrations of mixture of trichlorfon and SDS (0.0001 g/L trichlorfon + 0.5 g/L SDS, 0.1 g/L trichlorfon + 0.5 g/L SDS) and 0.0001 g/L trichlorfon, 0.1 g/L trichlorfon, 0.5 g/L SDS and control, were incubated simultaneously with homogenate of liver and muscle, respectively, at 25 °C for 60 min. After incubation, the content of reduced-glutathione (GSH) and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) in homogenate of liver were determined, and the activities of AChE in homogenate of muscle were also measured.Treatment with trichlorfon caused a significant concentration-dependent and time-related inhibition of AChE activity at all treatment concentrations and times since trichlorfon is a cholinesterase inhibitor. For the same trichlorfon treatment, an apparent decrease in GSH content was found in concentration of 0.01, 0.1, 1 g/L, whereas no significant alteration in antioxidant enzyme activity were found at all experiment concentrations and times, which might indicate that antioxidant enzymes have not involved in the metabolism of trichlorfon. The depletion of GSH might indicate that ROS could be involved in the toxic effects of trichlorfon. Exposure of SDS can inhibit activities of AChE, GST and CAT at concentrations of 0.5 and/or 1 g/L, which could be due to the denaturing process of SDS to the enzymes. For the mixture exposure of trichlorfon and SDS, the effect of the mixture of 0.0001 g/L trichlorfon and 0.5 g/L SDS on inhibition of AChE shows synergistic other than simple additive of trichlorfon and SDS. The combined effects of chemicals and detergents deserve to be particularly noted. It should be noted that the toxicity experiments were made in tissue homogenates instead of whole organisms. The responses against the toxic compounds will not be the same in both systems.     

Protective effect of vitamin C against chlorpyrifos oxidative stress in male mice

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of chlorpyrifos toward male mice and the oxidative stress of the sub-lethal dose (1/10 LD₅₀) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferase (GST) activities. Also, the protective effects of vitamin C (200 mg/kg body weight, bw) 30 min before or after administration of chlorpyrifos were investigated. The results demonstrated that the LD₅₀ value of chlorpyrifos was 134.95 mg/kg bw. The oral administration of 13.495 mg/kg chlorpyrifos significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD and GST. However, GPx activity remained unchanged, while the level of GSH and G6PD activity were decreased. Vitamin C treatment to chlorpyrifos intoxicated mice decreased LPO level and GST activity, normalized CAT, SOD and G6PD activities, while GSH content was increased. We conclude that vitamin C significantly reduces chlorpyrifos-induced oxidative stress in mice liver and the protective effect of the pre-treatment with vitamin C is better than the post-treatment.