Hepatic cytochrome P-450-dependent metabolism and enzymatic conjugation of foreign compounds in vitamin A-deficient rats

Abstract

The temporal effects of vitamin A deficiency on hepatic cytochrome P-450-dependent and conjugation reactions were studied in the rat. Cytochrome P-450 levels and N-methyl-p-chloroaniline N-demethylase activity were significantly reduced in the deficient animals. No other changes in parameters dependent on cytochrome P-450 were observed in vitro. Decreases in hepatic cytochrome P-450 were accompanied by a prolongation in hexobarbital sleeping times in deficient animals. The p-aminobenzoic acid N-acetyltransferase activity was higher in the deficient animals at 8 weeks, but by 10 weeks the activity in fact was significantly lower as compared to controls. Activities of 'native' and UDP N-acetylglucosamine 'activated' UDP-glucuronyltransferase were reduced in vitamin A deficiency. In contrast to this general pattern of impaired drug metabolism in vitamin A deficiency, glutathione S-aryltransferase activity was markedly enhanced at all time points from 4 to 10 weeks. Activities of this enzyme were twice controls at 6 weeks, a time at which no other enzyme changes were observed.