Inhibition of Fas/FasL mRNA expression and TNF-alpha release in concanavalin A-induced liver injury in mice by bicyclol

World J Gastroenterol. 2004 Jun 15;10(12):1775-9. doi: 10.3748/wjg.v10.i12.1775.

Abstract

Aim: Bicyclol, 4, 4'-dimethoxy-5, 6, 5', 6'-dimethylene-dioxy-2-hydroxymethyl -2'-carbonyl biphenyl, is a new anti-hepatitis drug. The aim of the present study was to investigate the protective effect of bicyclol on concanavalin A (Con A)-induced immunological liver injury in mice and its mechanism.

Methods: Liver injury was induced by injection of Con A via tail vein of mice and assessed biochemically and histologically. Serum transaminase and tumor necrosis factor alpha (TNF-alpha) were determined. Liver lesions were observed by light microscope. Expressions of TNF-alpha, interferon gamma (IFN-gamma), Fas and Fas ligand (FasL) mRNA in the livers were measured by RT-PCR.

Results: Serum transaminase level and liver lesions in Con A-induced mice were markedly reduced by oral administration of 100, 200 mg/kg of bicyclol. TNF-alpha level in serum was also reduced by bicyclol. Con A injection induced up-regulation of TNF-alpha, IFN-gamma, Fas and FasL mRNA expression in liver tissues. Bicyclol significantly down-regulated the expression of IFN-gamma, Fas and FasL mRNA, but only slightly affected TNF-alpha mRNA expression in liver tissues.

Conclusion: Bicyclol protects against Con A-induced liver injury mainly through inhibition of Fas/FasL mRNA expression in liver tissues and TNF-alpha release in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Concanavalin A
  • Fas Ligand Protein
  • Gene Expression / drug effects
  • Interferon-gamma / genetics
  • Male
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Transaminases / blood
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • fas Receptor / genetics*

Substances

  • Biphenyl Compounds
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Concanavalin A
  • Interferon-gamma
  • bicyclol
  • Transaminases