Inhibition of anti-Fas antibody-induced hepatitis by aminoguanidine in mice.
Aminoguanidine is an inhibitor of inducible nitric oxide synthase (iNOS) and is of potential clinical usefulness. Treatment of mice with anti-Fas antibodies (150 microg/kg, i.v.) induced elevation of plasma alanine aminotransferase activity at 4 h and this elevation was inhibited by pretreatment of mice with aminoguanidine (3, 10 and 30 mg/kg, i.p.). The anti-Fas antibody-induced elevation of caspase-3 activity was inhibited by aminoguanidine (30 mg/kg, i.p.), but the addition of aminoguanidine to the cytosol up to 10(-4) M did not inhibit the caspase-3 activity in vitro. Thus, aminoguanidine prevents anti-Fas antibody-induced hepatitis by affecting the apoptotic pathway upstream of caspase-3 activation.
Okamoto
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Research Laboratories, Nippon Chemiphar Co., Ltd, 1-22 Hikokawato, Saitama 341-0005, Misato, Japan. ncokamot@green.ocn.ne.jp
Okabe
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D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D020169:Caspases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000276:immunology*
D000906:Antibodies; D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D019014:fas Receptor; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001219:Aspartate Aminotransferases; D020169:Caspases; C004479:pimagedine