Failure of liver cirrhosis induction by thioacetamide in Nagase analbuminaemic rats.
Repeated administration of thioacetamide (TA), either intraperitoneally or in drinking water, produced liver cirrhosis in normal Sprague-Dawley rats (SDR) with significant histological alterations similar to those observed in human cirrhosis. In the present study, we evaluated the ability of TA to induce liver cirrhosis in mutant Nagase analbuminaemic SDR. Thioacetamide was administered either intraperitoneally up to 4 months or in drinking water up to 6 months to normal and to Nagase analbuminaemic SDR. Nagase analbuminaemic rats (NAR) were also administered TA in drinking water up to 10 months. Liver cirrhosis development was determined by macroscopic and microscopic analysis. In contrast to normal SDR, no histological characteristics of cirrhosis could be observed in NAR submitted to a 4 or 6 months treatment with TA. Such failure to induce cirrhosis in Nagase rats was confirmed even after prolonged TA administration in drinking water for up to 10 months. In contrast, fibrosis and cholangiolar proliferation occurred in the 10-month TA-treated analbuminaemic rats, suggesting that the mechanisms involved in cirrhosis induction are different from those involved in fibrosis development and carcinogenesis. It is unlikely that the protective effect against TA-induced cirrhosis observed in analbuminaemic rats is related to the absence of albumin in this rat strain, since a co-administration of TA with albumin in analbuminaemic rats did not restore the potential for TA to induce cirrhosis in this rat strain. In conclusion, the fact that induction of cirrhosis by TA is prevented in the inherently hyperlipidaemic and hypercholesterolaemic analbuminaemic rats could be considered for potential application in the treatment of clinical cirrhosis.
David
Pascale
P
Laboratoire de Chirurgie Expérimentale, Fondation Transplantation, 5, avenue Molière, 67200 Strasbourg, France.
Alexandre
Eliane
E
Chenard-Neu
Marie-Pierre
MP
Wolf
Philippe
P
Jaeck
Daniel
D
Richert
Lysiane
L
D000284:Administration, Oral; D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002761:Cholangitis / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000235:genetics; D007274:Injections, Intraperitoneal; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000172:deficiency* / Q000235:genetics; D013853:Thioacetamide / Q000008:administration & dosage / Q000633:toxicity*; D014881:Water Supply
D012709:Serum Albumin; D013853:Thioacetamide