Interaction of vitamin E and selenium with the hepatotoxic agent dimethylnitrosamine.
Pretreatment of rats with vitamin E, 0.02% w/w of the diet and a sc dose, 200 mg/kg, given 48 hrs. before dimethylnitrosamine, DMNA, was found to ameliorate the acute hepatotoxicity of DMNA (30 mg/kg) as reflected in reduced plasma asparagine-amino-transferase (AspAT) activity. This effect was confirmed by histological evaluation. No significant effect of DMNA on plasma levels of vitamin E was observed, however, DMNA significantly increased the hepatic level of vitamin E supplemented rats. Pretreatment with selenium, 0.5 mg/kg given intraperitoneally 48 hrs. before DMNA, was found to enhance the acute hepatotoxicity of DMNA as reflected in increased elevation of plasma AspAT activity. This effect was not confirmed morphologically. DMNA did not have any effect on the hepatic selenium state in selenium pretreated rats; however, selenium pretreatment tended to decrease hepatic and plasma tocopherol levels. To explain the effects observed in the present investigation, various mechanisms were discussed. If the compounds were acting as antioxidants, then the difference in intracellular localization had to be important. More likely a specific biochemical function involving drug metabolizing enzymes could be involved. Finally vitamin E could protect membranes from damage during the necrotizing action of DMNA.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D004128:Dimethylnitrosamine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology*; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology*
D009602:Nitrosamines; D014810:Vitamin E; D012643:Selenium; D004128:Dimethylnitrosamine