Allyl alcohol liver injury: suppression by ethanol and relation to transient glutathione depletion.
Rats metabolized a sublethal gastric dose (0.73 mmol/kg) of allyl alcohol (AIOH) within 10-15 min. Oxidation of AIOH to acrolein was accompanied by an equally rapid, but only transient depletion of hepatic reduced glutathione (GSH). GSH was restored to levels above normal within 5 hrs. Simultaneously, AIOH provoked marked elevation of alanine aminotransferase, gamma-glutamyl transpeptidase, and glutamate dehydrogenase activities in plasma and formation of lesions mainly in the periportal regions of the liver. Inhibition of alcohol dehydrogenase by 4-methyl pyrazole completely counteracted these effects. On the other hand, attempts to potentiate the toxicity of acrolein by the aldehyde dehydrogenase inhibitor cyanamide enhanced only the release of alanine aminotransferase. Co-administration of ethanol (3 g/kg) inhibited the rate of AIOH oxidation by more than 90%. Although with ethanol GSH remained depleted for several hours, the release of enzymes was markedly suppressed and the histologic changes completely prevented. These results indicate that the rapid rate of acrolein formation, rather than persistently lowered GSH content, is crucial in the hepatotoxicity of AIOH. They also suggest, that oxidation of acrolein via aldehyde dehydrogenase does not represent a major pathway for its detoxication in vivo.
D000433:1-Propanol / Q000097:blood / Q000633:toxicity; D000171:Acrolein / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002849:Chromatography, Gas; D000431:Ethanol / Q000494:pharmacology*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008297:Male; D020005:Propanols; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D020005:Propanols; D000431:Ethanol; C006463:allyl alcohol; D000171:Acrolein; D000433:1-Propanol; D000445:Aldehyde Oxidoreductases; D005969:Glutamate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D005978:Glutathione