Mechanisms of ethanol-drug-nutrition interactions.
Mechanisms of the toxicologic manifestations of ethanol abuse are reviewed. Hepatotoxicity of ethanol results from alcohol dehydrogenase-mediated excessive hepatic generation of nicotinamide adenine dinucleotide and acetaldehyde. It is now recognized that acetaldehyde is also produced by an accessory (but inducible) pathway, the microsomal ethanol-oxidizing system, which involves a specific cytochrome P450. It generates oxygen radicals and activates many xenobiotics to toxic metabolites, thereby explaining the increased vulnerability of heavy drinkers to industrial solvents, anesthetics, commonly used drugs, over-the-counter medications and carcinogens. The contribution of gastric alcohol dehydrogenase to the first pass metabolism of ethanol and alcohol-drug interactions is now recognized. Alcohol also alters the degradation of key nutrients, thereby promoting deficiencies as well as toxic interactions with vitamin A and beta-carotene. Conversely, nutritional deficits may affect the toxicity of ethanol and acetaldehyde, as illustrated by the depletion in glutathione, ameliorated by S-adenosyl-L-methionine. Other supernutrients include polyenylphosphatidylcholine, shown to correct the alcohol-induced hepatic phosphatidylcholine depletion and to prevent alcoholic cirrhosis in non-human primates. Thus, a better understanding of the pathology induced by ethanol has now generated improved prospects for therapy.
Alcohol Research and Treatment Center, VA Medical Center, Bronx, NY 10468.
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Lieber
D000079:Acetaldehyde / Q000378:metabolism / Q000633:toxicity; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000437:Alcoholism / Q000150:complications / Q000378:metabolism*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004347:Drug Interactions; D004361:Drug Tolerance; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000276:immunology; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000378:metabolism; D009748:Nutrition Disorders / Q000209:etiology*; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism
D004364:Pharmaceutical Preparations; D014801:Vitamin A; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D002374:Catalase; D000079:Acetaldehyde