Comparison of Murine Cirrhosis Models Induced by Hepatotoxin Administration and Common Bile Duct Ligation

Aim: To build up the research models of hepatic fibrosis in mice.

Methods: Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate (ANIT), allyl alcohol (AA), carbon tetrachloride (CCl(4)), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and silica, or subjected to common bile duct ligation (CBDL) to induce hepatic injury. Liver biopsies were performed every 4 wk to evaluate hepatic fibrosis over a period of 6 mo. Cumulative cirrhosis and survival curves were constructed by life table method and compared with Wilcoxon test.

Results: Under the dosages used, there was neither mortality nor cirrhosis in AA and silica-treated groups. DDC and ANIT caused cirrhosis within 4-12 and 12-24 wk, respectively. Both showed significantly faster cirrhosis induction at high dosages without significant alteration of survival. The duration for cirrhosis induction by CCl(4) ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl(4) dosage significantly worsened survival. Intraperitoneal CCl(4) administration resulted in better survival in comparison with gavage administration at high dosage, but not at medium and low dosages. After CBDL, all the mice developed liver cirrhosis within 4-8 wk and then died by the end of 16 wk.

Conclusion: CBDL and administrations of ANIT, CCl(4), and DDC ensured liver cirrhosis. CBDL required the least amount of time in cirrhosis induction, but caused shortened lives of mice. It was followed by DDC and ANIT administration with favorable survival. As for CCl(4), the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.