Abstract
Hepatic cytochrome P‐450 enzymes play important roles in bioactivation of chemical carcinogens, biotransformation of many endogenous compounds, and detoxification of numerous xenobiotics. These enzyme activities have been shown to be regulated by various dietary factors. In our previous study, hepatic cytochrome pentoxyresorufin O‐dealkylase (PROD) activity was decreased in rats fed an a‐tocopherol acetate‐deficient diet compared with rats fed α‐tocopherol acetate‐adequate or ‐supplemented diets. The objective of the present study was to investigate whether the modulatory effect of dietary a‐tocopherol acetate on hepatic cytochrome PROD activity is influenced by the presence of phénobarbital. Weanling male Sprague‐Dawley rats were fed the AIN‐76 diet for four days, fasted for two days, then fed semipurified diets that were a‐tocopherol acetate deficient, adequate, or supplemented with 5 and 15 g/kg a‐tocopherol acetate for four days. Liver and plasma a‐tocopherol concentrations were dose dependently regulated by dietary a‐tocopherol acetate level. Inhibition of lipid peroxidation by dietary a‐tocopherol acetate was dose dependent. Hepatic total cytochrome P‐450 content was significantly greater in rats fed diets supplemented with 5 and 15 g/kg a‐tocopherol acetate than in rats fed an a‐tocopherol‐adequate diet (p < 0.05). Hepatic cytochrome PROD activity was significantly greater in rats fed diets supplemented with 5 and 15 g/kg a‐tocopherol acetate than in rats fed a‐tocopherol acetate‐deficient and ‐adequate diets (p < 0.05). These results suggest that, in the presence of phenobarbital, dietary a‐tocopherol acetate efficiently affects tissue α‐tocopherol levels and inhibits lipid peroxidation and that diets supplemented with 5 or 15 g/kg a‐tocopherol acetate enhance hepatic cytochrome PROD activity compared with α‐tocopherol acetate‐deficient or ‐adequate diets.