Toxicological and Antioxidant Effects of Short-term Dehydroepiandrosterone Injection in Young Rats Fed Diets Deficient or Adequate in Vitamin E

This study examined the in vivo antioxidant and/or prooxidant effect of short-term dehydroepiandrosterone (DHEA) injection and the effect of dietary vitamin E. Male Sprague–Dawley rats (4 wk old) were fed vitamin E-deficient or vitamin E-adequate (30 mg dl-α-tocopheryl acetate/kg) diet for 4 weeks followed by intraperitoneal injection of DHEA for 1 week. The results showed that DHEA injection caused a dose-dependent decrease in body weight, and this effect was more pronounced in vitamin E-deficient rats. In contrast, DHEA injection significantly increased liver, kidney and adrenal weights. Hepatic vitamin E content was significantly lowered by vitamin E deficiency, which led to significantly increased ex vivo and iron-induced lipid peroxidation. DHEA injection did not affect hepatic vitamin E content but significantly decreased ex vivo and iron-induced lipid peroxidation in vitamin E-deficient rats. Hepatic total sulfhydryl (SH) groups and non-protein SH contents were not affected by vitamin E but were significantly increased by DHEA injection, which at 100 mg/kg was not more effective than at 50 mg/kg. Hepatic glutathione S-transferase (GST) activity was significantly decreased by DHEA, but vitamin E alleviated such a decrease. DHEA injection significantly increased hepatic glucose 6-phosphate dehydrogenase (G6PD) activity, and the effect was dose dependent in vitamin E-deficient rats. Thus, DHEA may compensate for vitamin E deficiency in vivo, and this effect is masked when dietary vitamin E is adequate. The antioxidant effect of DHEA is accompanied by decreased body weights, enlarged (fat-laden) tissues and altered activities of hepatic GST and G6PD.