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 5 mg/kg MD (MD), and rats treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage on 5 days a week for 4 weeks at a daily dose 5 mg/kg (MD and MD+Vit) using corn oil as the vehicle. Vitamins E and C were injected at doses of 50 mg/kg intramuscularly and 20 mg/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.

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), gamma-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.

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We have examined the effect of subchronic methidathion (MD) administration on heart damage, and have evaluated possible ameliorating effects of a combination of vitamins E and C against MD toxicity. The experimental groups were: control group, rats treated with 5 mg/kg MD and rats treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage 5 days a week for four weeks at a dose level of 5 mg/kg/day (MD and MD+Vit) by using corn oil as the vehicle. Vitamin E and vitamin C were injected at doses of 50 mg/kg i.m. and 20 mg/kg i.p., respectively, after the treatment with MD in the MD+Vit group. The levels of malondialdehyde (MDA) were determined in the heart tissue, and the levels of cardiac troponin I (TnI) in serum. An autoanalyser was used to determine the serum activities of cholinesterase (ChE). Histopathological examination was carried out in the heart tissue. MDA significantly increased in the MD group as compared to controls (P <0.01). When MD was given concurrently with vitamins E and C, the increase in MDA was significantly less (P <0.01). ChE activity significantly decreased in the MD group as compared to controls (P <-0.01). When MD was given concurrently with vitamins E and C, the decrease in ChE activity was significantly higher (P <-0.05). The serum TnI levels significantly increased in the MD group as compared to controls (P <-0.01). When MD was given concurrently with vitamins E and C, the increase in the serum TnI was significantly less (P <-0.01). MD caused the diffuse loss of striation and myocytolysis of the cardiomyocytes, whereas the combination of vitamins E and C caused a significant decrease in these effects of MD. In conclusion, subchronic MD administration caused heart damage and, in addition, treatment with a combination of vitamins E and C after the administration of MD reduced heart damage caused by MD.