Combination of systemic thioacetamide (TAA) injections and ethanol feeding accelerates hepatic fibrosis in C3H/He mice and is associated with intrahepatic up regulation of MMP-2, VEGF and ICAM-1

J Hepatol. 2006 Sep;45(3):370-6. doi: 10.1016/j.jhep.2006.03.017. Epub 2006 May 3.


Background/aims: The induction of liver fibrosis is difficult in mice. Here, we intended to improve fibrosis induction by combination of thioacetamide (TAA) injections and ethanol (EtOH) feeding and to characterize features of liver damage in this model. Most experimental therapeutic studies are performed in mice without pre-damaged livers.

Methods: C3H mice were injected three times/week (0.15 mg/g body weight) and fed with EtOH. Tissue and serum samples were collected and analysed.

Results: Portal fibrosis was verified by van Gieson staining showing a mild fibrosis (score F2) in TAA-treated mice and liver fibrosis (score F4) in the combination group using TAA/EtOH. Consonant with the histological results, the fibrosis marker MMP-2 and alpha 1 procollagen (I) were elevated at week 10 and 15 after treatment initiation in the combination group, whereas tissue protective proteinase, TIMP-1, was 18.5-fold increased only at week 10 but normalized until week 15. Fibrosis development was associated with elevated ICAM-1 expression.

Conclusions: Taken together, TAA/EtOH application was suitable to induce liver fibrosis characterized by typical bio-markers in C3H/He.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal*
  • Ethanol*
  • Gene Expression Regulation
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Liver / blood supply
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / physiopathology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Inbred C3H
  • Procollagen / genetics
  • Procollagen / metabolism
  • Thioacetamide*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Up-Regulation / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Biomarkers
  • Procollagen
  • Tissue Inhibitor of Metalloproteinase-1
  • Vascular Endothelial Growth Factor A
  • Thioacetamide
  • Intercellular Adhesion Molecule-1
  • Ethanol
  • Matrix Metalloproteinase 2