The effect of vitamin A deficiency on hepatic, renal and pulmonary glutathione S-transferase activities in the rat

Abstract

Feeding male weanling rats on a vitamin A deficient diet for 6 wk resulted in significant increases (44-57%) in glutathione S-aryl-, S-aralkyl-, S-alkyl- and S-epoxidetransferase activities in the liver cytosol. Only the S-aralkyl- (27%) and S-alkyltransferase (14%) activities were significantly increased in the kidney as a result of deficiency. There was no effect on any pulmonary glutathione S-transferase activity. The increases in hepatic transferase activities were due primarily to increases (25-96%) in the apparent Vmax. There were no changes in the apparent Km of any of the 4 drug substrates employed. With 3,4-dichloronitrobenzene as the 2nd substrate, the apparent Km for glutathione was increased by > 2-fold in vitamin A deficient livers compared with controls. The relationship between these results and enhanced susceptibility to chemical carcinogens in vitamin A deficiency is briefly discussed; comparison is made between the effects of this nutritional state and pretreatment with drug inducers on the glutathione S-transferases. [Glutathione S-transferases catalyze the metabolism of diverse foreign compounds, including chemical carcinogens. These transferases function non-enzymically to bind certain drugs reversibly and covalently and thereby decrease their potential toxicity.].