The protective effect of glycyrrhizin on anti-Fas antibody-induced hepatitis in mice.
Fas ligand, which is a type II membrane protein, is a major inducer of apoptosis. The effect of glycyrrhizin on anti-Fas antibody-induced hepatitis in mice was studied. Pretreatment of mice with glycyrrhizin (100, 200 and 400 mg/kg, i.p.) inhibited the anti-Fas antibody (150 microg/kg, i.v.)-induced elevation of plasma aminotransferase activity in a dose-dependent manner. CPP32 is a cystein protease and CPP32-like activity induced by anti-Fas antibody injection was inhibited by glycyrrhizin (200 mg/kg). However, the addition of glycyrrhizin (up to 10(-4) M) to a liver cytosol fraction isolated from mice treated with anti-Fas antibodies (150 microg/kg, i.v.) did not inhibit the CPP32-like activity in vitro. The present results clearly show that glycyrrhizin inhibited anti-Fas antibody-induced hepatitis by acting upstream of CPP32-like protease activation.
Okamoto
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Research Laboratories, Nippon Chemiphar, 1-22 Hikokawato, Misato, Japan.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D005260:Female; D019695:Glycyrrhizic Acid / Q000627:therapeutic use*; D006520:Hepatitis, Animal / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D019695:Glycyrrhizic Acid; D000410:Alanine Transaminase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases