t-686 and Shock--Septic

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.

Topics: Angiotensin III; Animals; Anticoagulants; Benzylidene Compounds; Blood Coagulation; Dose-Response Relationship, Drug; Endotoxins; Fibrinolysis; Heparin; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Plasminogen Activator Inhibitor 1; Shock, Septic; Succinimides; Survival Rate