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Egypt. J. Exp. Biol. (Zoo.). 2010; 6(2): 219-230


DIMETHOATE-INDUCED HEPATOTOXICITY IN RATS AND THE PROTECTIVE ROLES OF VITAMIN E AND N-ACETYLCYSTEINE

Ahmed M. Abu El-Saad Mohamed SA. Elgerbed.

Abstract
Dimethoate, an organophosphates pesticide, is used in controlling the pests of a variety of crops. Thus it is important to investigate the possible ways to ameliorate its toxicity. The aim of this study was to investigate the ameliorative effects of vitamin E alone and in combination with an antioxidant N-acetylcysteine (NAC) on some hepatic tissue enzyme activities and selected indices of oxidative stress in dimethoate-exposed rats. Eight groups of male Dawley rats were used in this study: control; dimethoate (D) group (orally administrated in a concentration of 21 mg/kg body weight); vitamin E group (200 mg/kg BW orally); NAC group (100 mg/kg BW i.p) and vitamin E+NAC group. The other three groups were orally administrated dimethoate in a concentration of 21 mg/kg BW followed by either vitamin E, NAC or vitamin E plus NAC in the same previous doses for 7 weeks. Oral administration of dimethoate induced a significant decrease in body weight and an increase in liver weight. Also, a highly significant increase in level of hepatic lipid peroxidation; significant decrease in the activities of antioxidant enzymes [superoxide dismutase, catalase and glutathione-S-transferase] were noticed at the end of the 7th week. Serum total protein, albumin, triglyceride, very low density lipoprotein cholesterol (VLDL-cholesterol) levels were decreased, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl-transferase (GGT), lactate dehydrogenase (LDH), and total cholesterol levels were increased significantly in the dimethoate-intoxicated rats. There was a statistically significant difference for all biochemical parameters except LDH when the vit.E + NAC + dimethoate-treated group was compared with the dimethoate-treated group. The present study also examined the genotoxic effect of vit.E and NAC in liver tissue of dimethoate-intoxicated rats. Analysis of DNA fragmentation (DNA damage) by gel electrophoresis was used. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern in dimethoate-intoxicated rats. Also it has been observed that vit.E and NAC selectively altered the extent of DNA damage. In combination, vit.E and NAC completely ameliorated the dimethoate-induced oxidative damage. Either compound alone was partially protective against dimethoate damage. In conclusion, the present results provide an evidence of beneficial effect of the antioxidant NAC in conjunction with vit.E in re-balancing the impaired prooxidant/ antioxidant ratio in sub-chronic dimethoate intoxication in rats.

Key words: Dimethoate, vitamin E, N-acetylcysteine, hepatotoxicity



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