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.
OBJECTIVE
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.
Kornek
Miroslaw
M
Department of Internal Medicine I, University Hospital Bonn, Germany.
Raskopf
Esther
E
Guetgemann
Ines
I
Ocker
Matthias
M
Gerceker
Sevil
S
Gonzalez-Carmona
Maria A
MA
Rabe
Christian
C
Sauerbruch
Tilman
T
Schmitz
Volker
V
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D013853:Thioacetamide; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D013853:Thioacetamide; D018799:Intercellular Adhesion Molecule-1; D000431:Ethanol; D020778:Matrix Metalloproteinase 2