The use of proteases as thrombolytic agents from the toxicological point of view

In case of systematic hyperproteolysis in the blood of experimental animals after application of ocrase, a fibrinolytically active protease from Aspergillus ochraceus, toxic side effects, particularly on hemostatis and cardiac action, were observed. In order to prevent toxic effects, ocrase in thrombolytic therapy is to be administered within the inhibitor level. After daily administration of 5.6 mg/kg of ocrase (50% of inhibitor level) to rats, toxicological examinations over four weeks showed no deviation from the regular hematological and biochemical values. The thrombolytic effect of ocrase is explained by the formation of an inhibitor-ocrase complex which acts thrombolytically in the presence of fibrin.