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Updated: Jul 20, 2026
08:56
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
A role for thrombin in liver fibrosis
J Gillibert Duplantier1, L Dubuisson, N Senant
1GREF, INSERM E362, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France.
Gut
|October 14, 2004
Summary
Thrombin inhibition with SSR182289 reduced experimental liver fibrosis in rats, particularly after seven weeks of carbon tetrachloride exposure. Early treatment also decreased fibrogenic cell activation markers.
Area of Science:
- Hepatology
- Fibrosis Research
- Pharmacology
Background:
- Thrombin, a serine proteinase, is implicated in liver fibrogenesis via procoagulant functions and receptor signaling.
- Experimental models are crucial for understanding liver fibrosis mechanisms.
Purpose of the Study:
- To investigate the therapeutic effect of thrombin inhibition on experimental liver fibrosis.
- To evaluate the impact of a thrombin antagonist on fibrotic markers and gene expression.
Main Methods:
- Carbon tetrachloride (CCl4) induced liver fibrosis in rats over three or seven weeks.
- Oral administration of thrombin antagonist SSR182289.
- Histomorphometry quantified fibrosis and alpha smooth muscle actin (ASMA) positive areas.
- Real-time RT-PCR measured fibrosis-related gene expression.
Main Results:
- After three weeks, SSR182289 significantly reduced ASMA positive cells (-22%) and TIMP-1 mRNA expression (-52%), but not overall fibrosis.
- After seven weeks, SSR182289 significantly decreased fibrosis (-30%) and ASMA positive areas (-35%).
- No effect on acute CCl4 toxicity markers (serum aminotransferases, necrosis).
Conclusions:
- Thrombin antagonism demonstrates potential in reducing liver fibrogenesis.
- Early intervention with SSR182289 may mitigate fibrogenic cell activation, indicated by ASMA and TIMP-1 modulation.
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