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Imidazolium salt attenuates thioacetamide-induced liver fibrosis in mice by modulating inflammation and oxidative stress.
- Source :
-
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver [Dig Liver Dis] 2012 Aug; Vol. 44 (8), pp. 665-73. Date of Electronic Publication: 2012 Apr 06. - Publication Year :
- 2012
-
Abstract
- Background and Aim: Oxidative stress contributes to liver fibrosis through the activation of hepatic stellate cells. In a cell-based screening study, a class of imidazolium salts demonstrates anti-fibrogenic properties. Little is known on imidazolium salt mechanistic effects. We investigated the anti-fibrogenic effect of one of the imidazolium salts, 1,3-bisbenzylimidazoliumbromide (DBZIM), in a chronic mouse model of liver fibrosis and evaluated the mechanism of this treatment.<br />Methods: Liver fibrosis was induced in mice by oral feeding of thioacetamide for 16 weeks. DBZIM was administered weekly, starting on the first day or 12 weeks from the day of thioacetamide administration. Hepatic function, histology and oxidative stress were examined. Expression of key inflammatory molecules and the molecular mechanism of DBZIM were assessed in hepatic stellate cells.<br />Results: DBZIM decreased the fibrogenic response in thioacetamide-mice as measured by collagen deposition and α-smooth muscle actin expression (P<0.01). DBZIM improved liver function and reduced both oxidative damage and inflammation (P<0.01). Most importantly, our findings report the discovery that astrocyte elevated gene-1, involved in tumour progression, was up-regulated in thioacetamide-mice and DBZIM modulated astrocyte elevated gene-1 and NF-κB expression.<br />Conclusion: These findings indicate DBZIM is a potent therapeutic agent for the treatment of liver fibrosis.<br /> (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- 8-Hydroxy-2'-Deoxyguanosine
Actins drug effects
Actins metabolism
Analysis of Variance
Animals
Cell Movement drug effects
Cells, Cultured
Collagen Type I metabolism
Collagen Type I, alpha 1 Chain
Cyclooxygenase 2 drug effects
Cyclooxygenase 2 metabolism
Deoxyguanosine analogs & derivatives
Deoxyguanosine metabolism
Gene Expression
Hepatic Stellate Cells drug effects
Hepatic Stellate Cells metabolism
Liver Cirrhosis chemically induced
Liver Cirrhosis pathology
Male
Membrane Proteins
Mice
NF-kappa B drug effects
NF-kappa B metabolism
Nerve Tissue Proteins drug effects
Nerve Tissue Proteins genetics
RNA-Binding Proteins
Superoxide Dismutase drug effects
Superoxide Dismutase metabolism
Thioacetamide
Up-Regulation
Imidazoles pharmacology
Inflammation metabolism
Liver Cirrhosis metabolism
Nerve Tissue Proteins metabolism
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3562
- Volume :
- 44
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 22483594
- Full Text :
- https://doi.org/10.1016/j.dld.2012.02.015