Interaction of ethanol with drugs, hepatotoxic agents, carcinogens and vitamins.
Ethanol has been shown to have a multitude of acute and chronic interactions with xenobiotic agents, many of which can now be explained on the basis of the existence of a newly recognized microsomal ethanol oxidizing system (MEOS) involving a specific cytochrome P-450 (P450IIE1). Although such a system was proposed already two decades ago, its role was viewed with skepticism: until recently, it was commonly believed that the primary pathway for hepatic ethanol metabolism is due almost exclusively to the activity of cytosolic alcohol dehydrogenase, with a minor contribution from peroxisomal catalase. It is now recognized, however, that liver microsomes (through MEOS) participate in ethanol metabolism. The existence of this system and its inducibility contribute to the metabolic tolerance to ethanol in the alcoholic. Cross induction of other microsomal enzymes also explains the tolerance to many commonly used drugs. Most importantly, the alcohol-inducible form (P450IIE1) has a unique capacity to activate xenobiotic agents to toxic metabolites, thereby explaining the unusual susceptibility of the alcoholic to the adverse effects of other drugs, hepatotoxic agents, carcinogens and even vitamins.
Lieber
C S
CS
Alcohol Research and Treatment Center, Bronx VA Medical Center, New York 10468.
D000426:Alcohol Dehydrogenase / Q000502:physiology; D000429:Alcohol Oxidoreductases / Q000502:physiology; D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology*; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D008113:Liver Neoplasms / Q000139:chemically induced*; D008930:Mitochondria, Liver / Q000201:enzymology
D002273:Carcinogens; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C092153:microsomal ethanol-oxidizing system; D000426:Alcohol Dehydrogenase