title: Imidazolium salt attenuates thioacetamide-induced liver fibrosis in mice by modulating inflammation and oxidative stress.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These findings indicate DBZIM is a potent therapeutic agent for the treatment of liver fibrosis.
authors.affiliation: Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, Singapore.
authors.forename: Nur-Afidah
authors.initials: NA
authors.lastname: Mohamed Suhaimi
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D016601:RNA-Binding Proteins; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D013853:Thioacetamide; D015854:Up-Regulation
chemical_list: C560871:1,3-bisbenzylimidazolium; D000199:Actins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D007093:Imidazoles; D008565:Membrane Proteins; C483038:Mtdh protein, mouse; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C544013:alpha-smooth muscle actin, mouse; D013853:Thioacetamide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D003849:Deoxyguanosine