Effect of the variations of S-adenosyl-L-methionine liver content on fat accumulation and ethanol metabolism in ethanol-intoxicated rats.
The protective effect of S-adenosyl-L-methionine against rat liver steatosis induced by chronic ethanol ingestion was investigated. S-Adenosyl-L-methionine given during ethanol treatment prevented steatosis and accelerated recovery from steatosis when given after ethanol withdrawal. It also caused a slight inhibition of blood ethanol consumption in both acutely and chronically intoxicated rats. About 30% inhibition of alcohol dehydrogenase, but not of the microsomal ethanol oxidation system, occurred in rats subjected to acute ethanol toxicity as well as in normal rats as a consequence of S-adenosyl-L-methionine treatment. A comparison between S-adenosyl-L-methionine and pyrazole, as concerns inhibition of ethanol oxidation and fat accumulation, revealed that a greater inhibition of ethanol metabolism by pyrazole was associated with incomplete prevention of steatosis, while a lower inhibition by S-adenosyl-L-methionine was coupled to a complete prevention. Ethanol induced a drastic decrease of reduced glutathione liver content as well as 630 and 133% increases of blood and liver acetaldehyde contents, respectively. S-Adenosyl-L-methionine treatment almost completely reconstituted the liver reduced glutathione pool and caused a large decrease of the liver and blood acetaldehyde contents. 1-Chloro-2,4-dinitrobenzene, which depletes the cellular reduced glutathione, and diethylethanolamine, an inhibitor of the phosphatidylethanolamine methylation, abolished the S-adenosyl-L-methionine-induced modifications of the reduced glutathione, acetaldehyde, and triacylglycerol contents in the liver of ethanol-treated rats. Neither S-adenosyl-L-methionine nor reduced glutathione inhibitors affected the liver acetaldehyde dehydrogenase activity. It is suggested that, although S-adenosyl-L-methionine induced a small inhibition of ethanol metabolism in the liver, its antisteatosic effect could largely depend on its role as a modulator of the reduced glutathione liver content.
D000079:Acetaldehyde / Q000032:analysis; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000378:metabolism*; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007275:Injections, Intravenous; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D000431:Ethanol; D012436:S-Adenosylmethionine; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D005978:Glutathione; D000079:Acetaldehyde