Chronic administration of ethanol with high vitamin A supplementation in a liquid diet to rats does not cause liver fibrosis. 2. Biochemical observations.
The inability of the 'ethanol/high vitamin A Lieber-DeCarli diet' to induce liver fibrosis in two different rat strains was further evaluated by determining changes in parameters of liver cell damage and of retinoid and lipid metabolism. In the ethanol/vitamin A-treated group, slight but constant hepatic cell damage, as indicated by elevated alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities in blood, was already observed at 6 months and maintained until the time of death at 16 months. Serum gamma-glutamyl transaminase activities were not raised. Moderate parenchymal liver cell damage was not accompanied by fibrosis. Hypertriglyceridemia or hypercholesterolemia were observed at 6-16 months of chronic alcohol administration. This response was strain dependent. In ethanol-treated rats of both strains, total liver retinoids and serum retinol concentrations were not altered. Therefore, the hypothesis that interaction between alcohol and retinoids is a major factor in the pathogenesis of alcoholic liver disease, needs to be reconsidered.
Seifert
W F
WF
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Bosma
A
A
Hendriks
H F
HF
Blaner
W S
WS
van Leeuwen
R E
RE
van Thiel-de Ruiter
G C
GC
Wilson
J H
JH
Knook
D L
DL
Brouwer
A
A
D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D014801:Vitamin A / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity
D014801:Vitamin A; D000431:Ethanol