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 mu g/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. (C) 2000 Elsevier Science B.V. All rights reserved.