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 wk but by 10 wk the activity was significantly lower as compared to controls. Activities of native and UDP N-acteylglucosamine 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 4-10 wk. Activities of this enzyme were twice controls at 6 wk, a time at which no other enzyme changes were observed. [The effects of vitamin A-deficiency on carcinogenesis are discussed.].