Uninterrupted prolonged ethanol oxidation as a main pathogenetic factor of alcoholic liver damage: evidence from a new liquid diet animal model.
Marked fatty infiltration and degenerative or mild inflammatory changes including eosinophilic cytoplasmic degeneration in centrilobular cells and focal inflammatory changes with cell necrosis were observed in livers of rats maintained for 12 weeks on a nutritionally adequate and balanced liquid ethanol diet. The animals continuously oxidized ethanol due to the supplementation of the diet with a low dose of 4-methylpyrazole (4-MP, an alcohol dehydrogenase inhibitor), that decreased ethanol elimination by about 20%. In other, equicalorically pair-fed groups of rats receiving (a) a similar ethanol-containing liquid diet without 4-MP or (b) a diet with 4-MP and 20% less ethanol, only a few minor changes were seen. The liver histology of rats pair-fed a control diet with a 4 times higher doses of 4-MP was completely normal. The results indicate that the prolonged imbalance of hepatic metabolism due to the uninterrupted oxidation of ethanol is a crucial factor in the development of alcoholic liver injury.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism*; D000077604:Fomepizole; D005526:Food, Formulated; D008099:Liver / Q000033:anatomy & histology; D008104:Liver Cirrhosis, Alcoholic / Q000209:etiology* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000008:administration & dosage / Q000097:blood; D051381:Rats; D013997:Time Factors
D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole