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

Abstract

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. 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. 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. 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.