Synergism between ethanol and carbon tetrachloride in the generation of liver fibrosis.
In this study, alcohol-induced histological lesions in a short-term experimental rat model were compared with those characteristic of human alcoholic liver disease. In the rat model used, pretreatment with carbon tetrachloride (CCl4) for 6 weeks was employed possibly to sensitize the liver for the effects of alcohol and shorten the time of induction of alcoholic liver disease. After 6 weeks of CCl4 treatment, subsequent maintenance on drinking water containing up to 10 per cent alcohol for 7 weeks potentiated liver fibroplasia as compared with non-alcohol-treated rats. However, steatosis and alcoholic hepatitis, as histological evidence for alcoholic liver disease as seen in humans, were not observed. In non-CCl4-pretreated control animals, alcohol administration had no effect on liver histology. It can be concluded that in the model used, CCl4 pretreatment sensitizes the liver to increase collagen deposition following alcohol administration, but not to steatosis or alcoholic hepatitis as seen in human alcoholic liver disease. In this experimental set-up, direct metabolic interaction of CCl4 with alcohol as a cause of the increased fibroplasia can be excluded.
Bosma
A
A
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Brouwer
A
A
Seifert
W F
WF
Knook
D L
DL
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004195:Disease Models, Animal; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN
D000431:Ethanol; D002251:Carbon Tetrachloride