Inhibition of ethanol induced hepatic vitamin A depletion by administration of N, N′-diphenyl-P-phenylene-diamine (DPPD)

Abstract

The administration of ethanol as 36% of the total calories in a nutritionally adequate liquid diet for three weeks to male Wistar rats caused a 36% decrease in hepatic vitamin A levels (P<0.001) when compared with glucose pair-fed control rats, without affecting serum levels of the vitamin. Simultaneous administration of a synthetic antioxidant, DPPD (N, N′-diphenyl- p-phenylene-diamine) to ethanol-fed rats caused a 73% decrease in the extent of the ethanol induced hepatic vitamin A depletion (P<0.001). DPPD administration did not affect weight gain, dietary (and hence ethanol) intake or serum ethanol and vitamin A levels in ethanol-fed rats, nor did it affect hepatic or serum vitamin A levels in pair-fed controls. Increased hepatic catabolism of retinoic acid due to induction of cytochrome P450 by ethanol has been suggested as a mechanism of depletion. In the current study, DPPD administration to ethanol-fed rats did not reverse the ethanol induced increase in microsomal cytochrome P450 concentrations or aniline hydroxylase activity. These findings indicate that the ethanol induced hepatic vitamin A depletion can be largely dissociated from the induction of cytochrome P450. In view of the potent free radical scavenging activity of vitamin A, and the protective effect of DPPD against ethanol induced hepatic loss of the vitamin, this study suggests that increased free radical generation and direct peroxidation of vitamin A may be an important mechanism by which ethanol induced hepatic vitamin A depletion occurs in the rat.