Pentoxifylline inhibits anti-Fas antibody-induced hepatitis by affecting downstream of CPP32-like activity in mice.
The effect of pentoxifylline on anti-Fas antibody-induced hepatitis was studied. The administration of anti-Fas antibodies (250 microg/kg, i.v.) to mice elevated plasma alanine aminotransferase (ALT) activity at 3 h. This anti-Fas antibody-induced elevation of ALT was inhibited by treatment with pentoxifylline at the doses of 10 and 100 mg/kg (i.p.). Anti-Fas antibody administration also elevated the CPP32-like protease activity in the liver at 3 h. Although pentoxifylline at 100 mg/kg, i.p., inhibited the anti-Fas antibody-induced elevation of plasma ALT, this treatment did not significantly inhibit the anti-Fas antibody-induced elevation of CPP32-like activity. The present results clearly showed that treatment with pentoxifylline inhibited anti-Fas antibody-induced hepatitis, at least in part, by affecting a reaction downstream of CPP32-like protease activation.
Okamoto
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Research Laboratories, Nippon Chemiphar Co., Ltd., Misato, Saitama 341-0005, Japan.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D010726:Phosphodiesterase Inhibitors; D019014:fas Receptor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D010431:Pentoxifylline