Abstract
It is known that endotoxin activates the complement system via the alternative pathway and induces many pathophysiological changes. We compared the effect of OKY, a specific thromboxane synthetase inhibitor, with that of FUT-175 (FUT), a protease inhibitor, on endoxin-induced decrease in platelet count and complement activation. OKY 10mg/kg and FUT 0.3mg/kg but not aspirin 1mg/kg, inhibited the decrease in platelet count induced by injection of endotoxin in rabbits. PGI2 10μg/kg also inhibited the endotoxin-induced platelet decrease. OKY markedly inhibited the endotoxin-induced increase in plasma TXB2 level and enhanced 6-keto-PGF1α level, but FUT did not. Endotoxin released lactate dehydrogenase (LDH) which is a marker enzyme of platelt lysis from rabbit plateets in vitro. FUT 10-5M and PGI2 3×10-7M, but not OKY 10-4M, inhibited the LDH release from platelets. FUT 10-6-10-5M dose-dependently inhibited the decrease in total hemolytic activity of complement system (CH 50). On the other hand PGI2 inhibited the binding of complement (C3 and C5) to guinea-pig platelets induced by endotoxin. These results suggest that OKY inhibited the decrease in platelet count induced by endotoxin may be due to formation of PGI2 which inhibits the binding of complement to platelet, while FUT inhibited this via inhibition of complement activation.
