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


CONCLUSIONS
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.
Li
Min
M
Department of Pharmacology, Institute of Materia Medica and Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
Liu
Geng-Tao
GT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003208:Concanavalin A; D053222:Fas Ligand Protein; D015870:Gene Expression / Q000187:drug effects; D007371:Interferon-gamma / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics*
D001713:Biphenyl Compounds; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D003208:Concanavalin A; D007371:Interferon-gamma; C477843:bicyclol; D000637:Transaminases