Attenuation of hepatic fibrosis by an imidazolium salt in thioacetamide-induced mouse model
Article first published online: 19 DEC 2012
© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 28, Issue 1, pages 188–201, January 2013
How to Cite
Ding, Z. and Zhuo, L. (2013), Attenuation of hepatic fibrosis by an imidazolium salt in thioacetamide-induced mouse model. Journal of Gastroenterology and Hepatology, 28: 188–201. doi: 10.1111/j.1440-1746.2012.07265.x
- Issue published online: 19 DEC 2012
- Article first published online: 19 DEC 2012
- Accepted manuscript online: 18 SEP 2012 08:05AM EST
- Manuscript Accepted: 19 AUG 2012
- Institute of Bioengineering and Nanotechnology
- hepatic stellate cells;
- imidazolium salts;
- matrix metalloproteinases;
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.
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 8th 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.
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)-β 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.
DPIM reduced fibrosis in the thioacetamide-induced mouse liver fibrosis model, and warranted further studies for possible clinical application in the future.