Effect of a necrogenic dose of diethylnitrosamine on vitamin E-deficient and vitamin E-supplemented rats

In order to evaluate the effects of a necrogenic dose of diethylnitrosamine (DEN) on vitamin E-deficient and vitamin E-supplemented rats, a single dose of the drug (200 mg/kg body-weight) was injected intraperitoneally at the end of 10 weeks of treatment with the diets. The hepatic necrosis and lipoperoxidation provoked by DEN were evaluated 24, 48, 72 and 120 hours after the injection and were found to be more intense in the deficient group (thiobarbituric acid reactive substances (TBARS): 5.20 +/- 1.48 nmol/mg protein; necrosis volume: 68.99 +/- 8.36%; P < 0.05) during the second period. Also, in the same group and during the same period, mean plasma and hepatic vitamin E concentrations and mean liver glutathione concentration were the lowest detected, suggesting the occurrence of antioxidant consumption due to the toxic action of DEN. In contrast to vitamin E deficiency, which permitted the drug to exert stronger toxic effects, 20-fold supplementation with vitamin E did not provide additional protection against the lipoperoxidation and necrosis provoked by DEN (P < 0.05). The results suggest that other mechanisms in addition to lipoperoxidation provoked by free radicals originating from the metabolism of nitrosamines by the cytochrome P-450-dependent enzymatic system may be involved in the hepatotoxic action of these substances. (C) 1998 Elsevier Science Ltd. All rights reserved.