Ethanol-induced hepatotoxicity; experimental observations on the role of lipid peroxidation.
Hepatic lipid peroxidation in vivo or in vitro as measured by UV absorption spectra of microsomal lipids or by production of TBA-reacting substances by whole liver homogenates, was studied after acute or during prolonged administration of ethanol. No evidence of peroxidative derangement of liver microsomal lipids in vivo was detected in either experimental situation, while the production of TBA-reacting substances by pooled liver homogenates incubated in vitro appeared slightly increased. Treatment with reduced glutathione (GSH and 2-mercaptopropionylglycine (2-MPG) was able to reduce fatty liver in acute and prolonged ethanol dosing, as well as the production of TBA-reacting compounds. Similar effects were obtained with 3-amino-1,2,4-triazole which was assayed only in acute experiments. By contrast, hepatic triglyceride accumulation induced by a single intoxicating dose of ethanol was not affected by preventive treatment with pyrazole which seemed to act as a pro-oxidant agent as far as the production of TBA-reacting substances is concerned. The role of lipid peroxidation as a pathogenic mechanism for acute and chronic ethanol-induced hepatotoxicity is discussed in relation to the action of anti-oxidant compounds which are active in preventing liver injury. It is concluded that lipid peroxidation is unlikely to be an important mechanism in alcohol hepatotoxicity.
D000818:Animals; D001975:Bromotrichloromethane / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D013858:Thiobarbiturates / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D010545:Peroxides; D013858:Thiobarbiturates; D014280:Triglycerides; D000431:Ethanol; D001975:Bromotrichloromethane