Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2005; 11(27): 4167-4172
Published online Jul 21, 2005. doi: 10.3748/wjg.v11.i27.4167
Comparison of murine cirrhosis models induced by hepatotoxin administration and common bile duct ligation
Ming-Ling Chang, Chau-Ting Yeh, Pei-Yeh Chang, Jeng-Chang Chen
Ming-Ling Chang, Chau-Ting Yeh, Liver Research Unit, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, China
Pei-Yeh Chang, Jeng-Chang Chen, Department of Surgery, Chang Gung Children’s Hospital, Taoyuan, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by the Chang Gung Memorial Hospital, Taoyuan, Taiwan, China, CMRPG 33014, CMRPG 33063 and CMRP 800
Correspondence to: Jeng-Chang Chen, Department of Surgery, Chang Gung Children’s Hospital, 5 Fu-Shin Street, Kweishan, 333, Taoyuan, Taiwan, China. jengchang@so-net.net.tw
Telephone: +886-3-3281200-8227 Fax: +886-3-3287261
Received: October 20, 2004
Revised: December 20, 2004
Accepted: December 23, 2004
Published online: July 21, 2005
Abstract

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 (CCl4), 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 CCl4 ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl4 dosage significantly worsened survival. Intraperitoneal CCl4 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, CCl4, 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 CCl4, the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.

Keywords: Common bile duct ligation; Fibrosis; Hepatotoxin; Liver; Mice