Attenuation of hepatic fibrosis by an imidazolium salt in thioacetamide-induced mouse model.
J Gastroenterol Hepatol
; 28(1): 188-201, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-22989190
ABSTRACT
BACKGROUND AND AIM:
Hepatic fibrosis is a worldwide healthy burden associated with significant morbidity and mortality. It is caused by a variety of chronic liver injuries. There is currently no effective treatment for liver fibrosis. In this report, we tested an imidazolium salt, 1,3-diisopropylimidazolium tetrafluoroborate (DPIM), for its anti-fibrotic properties in the thioacetamide-induced mouse model.METHODS:
DPIM was orally delivered to the thioacetamide-treated mice via drinking water for 12 weeks at the onset of thioacetamide treatment at a concentration of 0.1% (prevention group), and for 4 weeks starting at the 8(th) week at a concentration of 0.1% or 0.2% (attenuation group), respectively. Messenger RNA and protein were determined by real-time polymerase chain reaction and Western blotting, matrix metalloproteinase (MMP) activities were measured by fluorogenic peptide substrate and zymography. Mitogen-activated protein kinase (MAPK) and PI3K inhibitors were applied in HSC-T6 cells in combination of DPIM to probe possible signal pathways underlying the compound's action.RESULTS:
We observed a significant reduction in collagen deposition in both prevention and attenuation groups. The α-smooth muscle actin (SMA) and transforming growth factor (TGF)-ß gene expressions were also reduced in both groups. The reduction of collagen deposition could be in part attributed to the suppression of CCR-2 expression and the enhanced matrix protein remodeling by metalloproteinases, especially MMP-3. MAPK and PI3K signaling pathways may be partially participated in DPIM's molecular action.CONCLUSION:
DPIM reduced fibrosis in the thioacetamide-induced mouse liver fibrosis model, and warranted further studies for possible clinical application in the future.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article