Protective Effect of T-686, an Inhibitor of Plasminogen Activator Inhibitor-1 Production, Against the Lethal Effect of Lipopolysaccharide in Mice

Abstract

We have examined the effects of an inhibitor of plasminogen activator inhibitor-1 (PAI-1) production, (3E,4E)-3-benzylidene-4-(3,4,5-trimethoxy-benzylidene)pyrrol idine-2,5-dione (T-686), on lipopolysaccharide (LPS)-induced death in mice. Oral administration of T-686 (10 and 100 mg/kg/day) for 8 days prior to the LPS injection (35 mg/kg, i.v.) protected mice from the lethal effect of LPS in a dose-dependent fashion. Moreover, treatment with 100 mg/kg T-686 attenuated the increase in plasma PAI-1 activity and the decrease in AT-III activity induced by LPS. We conclude that T-686 can reduce the mortality of mice induced by LPS, which seems to be partially correlated with both hypercoagulation and hypofibrinolysis.