Effects of chronic ethanol administration in the rat: Relative dependency on dietary lipids—I.: Induction of hepatic drug-metabolizing enzymes in vitro

Abstract

Female Sprague-Dawley rats were fed nutritionally adequate liquid diets with or without ethanol, at two ethanol concentrations, 5 and 6% (w/v). In other animals, various degrees of caloric deficiency were obtained by replacing ethanol by water in one animal of a pair. Ethanol given as a 5% (w/v) solution with high amounts of dietary fat increased cytochrome P-450, the activities of NADPH-cytochrome P-450 reductase, benzphetamine demethylation, aniline hydroxylation and microsomal ethanol-oxidizing system (MEOS). When ethanol was given with a low fat diet as a 5% (w/v) solution, the increase in cytochrome P-450 and P-450 reductase was much less than with a high fat diet; the other enzyme activities, however, were enhanced to a level comparable to that achieved with the high fat diet. When ethanol was administered as a 6% (w/v) solution in presence of a low fat diet, caloric deficiency was observed and no significant induction of any parameter except aniline hydroxylation could be found. When it was given with a high fat diet, in spite of caloric deficiency and lower ethanol ingestion, cytochrome P-450 and P-450 reductase activities were enhanced while that of MEOS was not. Ingestion of ethanol as a 6% (w/v) solution with a high fat diet resulted in a negligible weight gain. Higher basal levels of cytochrome P-450, P-450 reductase and benzphetamine demethylation activities were found in animals rendered caloric-deficient. Ethanol is associated with a greater induction of drug-metabolizing enzyme activities in the high fat model compared to the low fat model. Induction of drug-metabolizing enzymes by ethanol is partly dependent on dietary lipids as well as on the amounts of ethanol ingested and on the caloric status of the animal.