Toshihiro Okamoto (1), Yuji Hitomi (2) and Atsuko Hara (1)
(1) Research Laboratories, Nippon Chemiphar Co., Ltd., 1-22 Hikokawato, Misato, Saitama 341-0005, Japan
(2) Zeria Pharmaceutical Co., Ltd., Ohsato-gun, Saitama 360-0111, Japan
Abstract: The effect of cyclosporine A (CsA) on anti-Fas antibody-induced hepatitis was studied. The administration of anti-Fas antibody (250 microg/kg) to mice elevated plasma alanine aminotransferase (ALT) activity at 3 hr. This anti-Fas antibody-induced elevation of ALT was inhibited by treatment with CsA (10, 30 and 100 mg/kg) in a dose-dependent manner. Anti-Fas antibody administration elevated CPP32-like protease activity at 3 hr in mouse liver, and this elevation of CPP32-like activity was inhibited by treatment with CsA. The present results show that CsA treatment inhibits the anti-Fas antibody-induced apoptotic process of hepatitis, at least in part, by affecting a reaction upstream of CPP32-like protease activation.
Keywords: Fas, Cyclosporine A, Liver