ROLE OF ETHANOL IN FREE RADICAL GENERATION

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Alcohol may cause deterioration of membrane structure and function due to the enhancement of free radical formation. The overall objective of this proposal is to investigate how alcohol ingestion may cause membrane alteration through this mechanism. Specifically, experiments will' be designed to (1) study the mechanism of free radical formation as induced by ethanol, (2) test the hypothesis that free radicals may play a: major role in alcohol-induced liver injury, (3) evaluate the effects of chronic alcohol ingestion on specific membrane function and structure, (4) evaluate the body's protective system in liver and blood cell membranes against the toxic effects of free radicals and (5) investigate the effects of dietary antioxidants, such as vitamin E, in protecting against the peroxidation effects of alcohol. The technique of electron spin resonance spectroscopy for the detection and identification of free radicals will be employed. Due to the physiological and behavioral similarity of Sinclair (S- l) miniature swine to humans, these animals will be used for studying the effect of acute and chronic ethanol ingestion on blood cells and liver membranes. These swine are especially suitable for alcohol studies because they are known to consume ethanol voluntarily. Most studies proposed will utilize the red blood cell ghost and the subcellular membranes from liver biopsy samples. Membrane lipid composition, especially polyunsaturated fatty acid profile of phospholipids, and some membrane-bound activities such as ATPases will be examined after acute and chronic ethanol administration. Activity of enzymes involved in the body's protective system against active oxygen species, such as superoxide dismutase, catalase and gluthatione peroxidase will be evaluated also. It is anticipated that through this investigation, useful information may be obtained regarding the mechanism of membrane deterioration due to alcohol ingestion. ln addition, information will be obtained regarding the effectiveness of dietary supplement of vitamins E and C in alleviating some of the changes due to alcohol abuse.