Irfan Altuntas

The effects of organophosphate insecticide methidathion on lipid peroxidation and anti-oxidant enzymes in rat erythrocytes: role of vitamins E and C

The effects of organophosphate insecticide methidathion (MD) on lipid peroxidation and anti-oxidant enzymes and the ameliorating effects of a combination of vitamins E and C against MD toxicity were evaluated in rat erythrocytes. Experimental groups were: control group, MD-treated group (MD), and MD+vitamin E+vitamin Ctreated group (MD+Vit). MD and MD+Vit groups were treated orally with a single dose of 8 mg/kg MD body weight at 0 hour. Vitamins E and C were injected at doses of 150 mg/kg body weight, i.m. and 200 mg/kg body weight, i.p., respectively, 30 min after the treatment of MD in the MD+Vit group. Blood samples were taken 24 hours after the MD administration. The level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were studied in the erythrocytes. MDA level increased significantly in the MD group compared to the control group (P <0.05) and decreased significantly in the MD+Vit group compared to the MD group (P <0.05). The activities of SOD, GSH-Px, and CAT decreased in the MD group compared to the control group (P<0.05). Only GSH-Px activity increased in the MD+Vit group compared with the MD group. These results suggest that treating rats with MD increases LPO and decreases anti-oxidant enzyme activities in erythrocytes. Furthermore, single-dose treatment with a combination of vitamins E and C 30 min after the administration of MD can reduce LPO caused by MD.

Nephrotoxicity in rats induced by chlorpryfos-ethyl and ameliorating effects of antioxidantsy

Nephrotoxicity induced by chlorpyrifos-ethyl (CE) and ameliorating effects of melatonin and vitamin E plus vitamin C were evaluated in rats exposed to CE. Experimental groups were as follows: control (C), CE treated (CE), vitamin E plus vitamin C treated (Vit), melatonin treated (Mel), vitamin E plus vitamin C plus CE treated (Vit+CE), and melatonin plus CE treated (Mel+CE). The rats in the CE, Vit+CE and Mel+CE groups were administered orally with CE in two equal doses of 41 mg/kg body weight (0.25 LD50). Melatonin and vitamins E and C were administrated intramuscularly at the doses of 10, 150 and 200 mg/kg, respectively. The levels of thiobarbituric acid reactive substance (TBARS) and antioxidant potential (AOP), and the activities of glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. There were no significant differences in the activities of SOD and CAT between the experimental groups. The level of TBARS increased significantly (P<0.05) while AOP decreased significantly (P<0.05) in the CE group compared with the C group. GSH-Px activity was significantly (P<0.05) lower in the CE group and higher in the melatonin group than the control group. Histopathological changes were found in the kidney tissue of rats treated with CE. These were infiltration in mononuclear cells at perivascular and peritubular areas, hydropic degenerations in tubule epithelium and glomerular sclerosis. The severity of the lesions was reduced by administration of vitamins and melatonin. These results suggest that CE increases lipid peroxidation and decreases AOP by increasing oxidative stress, and that high doses of melatonin and a combination of vitamin E plus vitamin C considerably reduce the toxic effect of CE on kidney tissue of rats.

The effects of diazinon on lipid peroxidation and antioxidant enzymes in erythrocytes in vitro.

Diazinon is one of the most widely used organophosphate insecticides (OPI) in agriculture and public health programs. The aim of this study was to investigate how an OPI, diazinon, affects lipid peroxidation (LPO) and the antioxidant defense system in vitro. For this purpose, two experiments were carried out. In experiment 1, the effects of various concentrations of diazinon on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in erythrocytes were studied. Each diazinon concentration was incubated with a previously prepared erythrocyte samples at +4°C for 0, 60 and 180 min. After incubation, the malondialdehyde (MDA) levels and the activities of SOD, GSH-Px and CAT were determined. In experiment 2, in order to determine the direct effect of diazinon on the activities of SOD, GSH-Px and CAT, the erythrocytes were haemolysed and incubated with the various concentrations of diazinon at +4°C for 0, 60 and 180 min. In experiment 1, MDA levels and the activities of SOD and GSH-Px increased with increasing diazinon concentration and incubation period, but CAT activity remained unchanged. In experiment 2, SOD activity was significantly decreased, and GSH-Px activity was significantly increased. From these results, it can be concluded that in vitro administration of diazinon results in the induction of erythrocyte LPO and changes the activities of antioxidant enzymes, suggesting that reactive oxygen species may be involved in the toxic effects of diazinon.

The effects of methidathion on lipid peroxidation and some liver enzymes: role of vitamins E and C

Abstract. Methidathion (MD) [O,O-dimethyl S-(2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl) phosphorodithioate] is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programmes. We have, therefore, examined the in vivo and in vitro effects of MD on the serum activities of cholinesterase (ChE), enzymes concerning liver damage and lipid peroxidation (LPO; only in vivo), and have evaluated the ameliorating effects of a combination of vitamins E and C against MD toxicity. The in vivo experimental groups were: control group, MD-treated group (MD), and a group treated with MD plus vitamin E plus vitamin C (MD+Vit). The MD and MD+Vit groups were treated orally with a single dose of 8xa0mg MD/kg body weight at 0xa0h. Vitamin E and vitamin C were injected at doses of 150xa0mg/kg body weight i.m. and 200xa0mg/kg body weight i.p., respectively, 30xa0min after the treatment with MD in the MD+Vit group. Blood samples were taken 24xa0h after the MD administration. For in vitro study, venous blood samples were obtained from volunteers, and serum recovered. The activities of serum enzymes were determined in each sample and these served as 0xa0h values. Each sample was divided into four portions, each of which served as one of the experimental groups, as follows: control group, vitamin E plus vitamin C group (Vit), MD-treated group (MD) and MD plus vitamin E plus vitamin C group (MD+Vit). Vitamin E and vitamin C were added at doses of 7.5 and 10xa0µg/ml, respectively, into the Vit and MD+Vit groups. MD was added at doses of 0.4xa0mg/ml into the MD and MD+Vit groups. The activities of serum enzymes were determined in each sample at 24xa0h. The results of the in vivo experiment demonstrated that thiobarbituric acid reactive substances were increased in the MD group compared with the control group, and decreased in the MD+Vit group compared with MD group. ChE activity was decreased in both MD and MD+Vit groups compared with controls and increased in the MD+Vit group compared with the MD group. The activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) were increased in both the MD and MD+Vit groups compared with the control group. AST activity was decreased in MD+Vit group compared with the MD group. Alanine aminotransferase (ALT) activity was decreased in both the MD and MD+Vit groups compared with control group. The results of in vitro experiment showed that all enzyme activities remained unchanged in both the control and Vit groups compared with values at 0xa0h. The activities of ChE, ALT and LDH were decreased in both the MD and MD+Vit groups compared with 0xa0h values. There was no significant difference between the MD and MD+Vit groups. The activities of AST, ALP and GGT remained unchanged in all groups. From these results, it can be concluded that MD caused liver damage, and LPO may be one of the molecular mechanisms involved in MD-induced toxicity. Single-dose treatment with a combination of vitamins E and C after the administration of MD can reduce LPO caused by MD.

Lithium-induced renal toxicity in rats: Protection by a novel antioxidant caffeic acid phenethyl ester

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li2CO3 solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 μM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-β-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.

Role of reactive oxygen species in organophosphate insecticide phosalone toxicity in erythrocytes in vitro

Reactive oxygen species (ROS) caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study we aimed to investigate how an organophosphate insecticide, phosalone, affects lipid peroxidation (LPO) and the antioxidant defence system in vitro. For this purpose, the effects of various doses of phosalone on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in erythrocytes were studied. Each phosalone dose was incubated with a previously prepared erythrocyte sample at +4 degrees C for 0, 60 and 180 min. After incubation, the levels of malondialdehyde (MDA) and the activities of SOD, GSH-Px and CAT were determined. Phosalone caused an increase in MDA formation and a decrease in the activities of SOD, GSH-Px and CAT. However, these effects were seen only at extremely high concentrations of phosalone and these concentrations were in the lethal range. Therefore, we suggest that ROS may not involve in the toxic effects of the pesticidal use of phosalone in low concentrations.

Vascular wall damage in rats induced by methidathion and ameliorating effect of vitamins E and C

We examined the effect of subacute methidathion (MD) administration on vascular wall damage and evaluated the ameliorating effects of combination of vitamins E and C against MD toxicity. The experimental groups were: rats treated with corn oil (control group), rats treated with 5xa0mg/kg MD (MD), and rats treated with 5xa0mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage on 5xa0days a week for 4xa0weeks at a daily dose 5xa0mg/kg (MD and MD+Vit) using corn oil as the vehicle. Vitamins E and C were injected at doses of 50xa0mg/kg intramuscularly and 20xa0mg/kg intraperitoneally, respectively, after the treatment with MD in the MD+Vit group. The levels of malondialdehyde (MDA) were determined in the aortic tissue. Histopathological examination was examined in the thoracic aortic tissue. MDA levels were higher in the MD group than the control group and lower in the MD+Vit group than MD group. MD administration led to irregulation, prominent breaks, and fragmentation of the elastic fibers but decrease in the irregulation and fragmantation of the elastic fibers with the combination of vitamins E and C in MD-treated rats. In conclusion, it is likely that subacute MD administration caused vascular wall damage, and that treatment with a combination of vitamins E and C after the administration of MD can reduce vascular wall damage caused by MD.

The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat heart and ameliorating role of vitamin E and vitamin C

Diazinon is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programs. Reactive oxygen species (ROS) caused by OPIs may be involved in the toxicity of various pesticides. The aim of this study was to investigate how diazinon affects lipid peroxidation (LPO) and the antioxidant defense system in vivo and the possible ameliorating role of vitamins E and C. For this purpose, experiments were done to study the effects of DI on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in adult rat heart. Experimental groups were: (1) control group, (2) diazinon treated (DI) group, (3) DI+vitamins E and C-treated (DI+Vit) group. The levels of malondialdehyde (MDA) and the activities of SOD and CAT increased significantly in the DI group compared with the control group. The activity of SOD and the levels of MDA decreased significantly in the DI+Vit group compared with the DI group. The differences between the DI+Vit and control groups according to the MDA levels and the activities of both SOD and CAT were statistically significant. These results suggest that treating rats with a single dose of diazinon increases LPO and some antioxidant enzyme activities in the rat myocardium and, in addition, that single-dose treatment with a combination of vitamins E and C after the administration of diazinon can reduce LPO caused by diazinon, though this treatment was not sufficiently effective to reduce the values to those in control group.

Clinical importance of erythrocyte malondialdehyde levels as a marker for cognitive deterioration in patients with dementia of Alzheimer type: a repeated study in 5-year interval

OBJECTIVESnThe aim of the present study was to determine the effects of aging and dementia of the Alzheimer type (DAT) on lipid peroxidation and antioxidant enzyme activities.nnnDESIGN AND METHODSnTwenty-six patients with DAT were included in the present study. Group I: 26 patients diagnosed as DAT and studied 5 yr ago. Group II: This group consisted of the same patients as Group I at the present time. Activities of CuZn superoxide dismutase (CuZn SOD) and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) concentrations of these 26 subjects were measured and mini mental state examination (MMSE), brief psychiatric rating scale (BPRS), Hamilton depression rating scale (HDRS) were applied.nnnRESULTSnThe results revealed that 26 dementia patients had worsened cognitive symptoms and significantly increased CuZn SOD and MDA levels and decreased GSH-Px levels after 5 yr. Significant correlation was found between age and CuZn SOD (r: +0.406, p: 0.034), and between MMSE and MDA (r: -0.411, p: 0.032).nnnCONCLUSIONSnWe can conclude that MDA, CuZn SOD, and GSH-Px were significantly affected in the patients with Alzheimer disease. The most striking finding of this study is the significant correlation between MMSE and MDA in patients with DAT.

The effects of subchronic methidathion toxicity on rat liver: role of antioxidant vitamins C and E.

Methidathion (MD) phosphorodithioic acid S-[(5-methoxy-2-oxo-1,3,4-thiadiazol-3(2H)-yl)methyl] O,O-dimethyl ester is the organophosphate insecticide (OPI) most commonly used worldwide in the pest control of crops. Subchronic MD exposure was evaluated for its effects on lipid peroxidation, the serum activities of cholinesterase (ChE), and enzymes concerning liver damage, and the protective effects of combination of vitamins E and C in albino rats. Additionally, the histopathological changes in liver tissue were examined. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body wight MD plus vitamin E plus vitamin C (MD+AO group). The MD and MD+AO groups were treated orally with MD on five days a week for 4 weeks. The serum activities of cholinesterase (ChE), alanine transferase (ALT), aspartate amiotransferase (AST), lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and the concentration of malondialdehyde (MDA) and liver histopathology were studied. In serum samples, MD significantly increased MDA concentration and ALP, AST, GGT, LDH activities but decreased the ALT and ChE activities. In the MD+AO group, MDA level and ALP, AST, LDH activities were significantly decreased and ChE activity was increased compared to the MD group. Histopathological changes found in liver tissue of rats treated with MD included were infiltration with mononuclear cells in all portal areas, sinusoidal dilatation, and focal microvesicular steatosis and hydropic degenerations in parenchymal tissue. The severity of these lesions was reduced by administration of vitamins. From these results, it can be concluded that subchronic MD causes liver damage, and lipid peroxidation may be a molecular mechanism involved in MD-induced toxicity. Furthermore, the combination of vitamins E and C can reduce the toxic effects of MD on liver tissue of rats.