Ethanol and Biological Membranes: Experimental Studies and Theoretical Considerations

Abstract

An enigma facing investigators who seek to explain the pathogenesis of ethanol-induced diseases is the wide variety of tissues and organs affected by this compound. Moreover, the effects of acute and chronic ethanol intoxication are not only different, but often of an opposite nature. Whereas acute ethanol intoxication exerts only reversible functional changes, chronic abuse may lead to significant degenerative and inflammatory diseases of many organs, including the liver, pancreas, brain, heart, and skeletal muscle (Majchrowicz and Noble 1979). Oxidation of ethanol by the liver results in an early increase in the hepatic reduced nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide (NADH-NAD) ratio, but after chronic consumption this ratio returns to normal (Williamson et al. 1969). In extrahepatic organs, little metabolism of ethanol takes place (Erickson 1979). While acetaldehyde, the primary metabolite of ethanol oxidation, might react with cell constituents in the liver, the organ where it is produced, circulating levels of acetaldehyde are so low that it is unlikely to play a role in diseases of other organs, e.g., heart or brain (Erickson et al. 1982). For these and other reasons, it appears unlikely that the metabolism of ethanol can be incriminated as the cause of the widespread manifestations of ethanol-induced maladies. In recent years, we and others have been intrigued by the observations which indicate that ethanol acts on all biological membranes as a physical agent, similarly to other anesthetics.