Antithrombotic effect of a novel protein from Fusarium sp. CPCC 480097 in a rat model of artery-vein bypass thrombosis

Abstract

Context: The incidence and mortality of thrombotic disorders are rapidly increasing throughout the world. Therefore, attempts have been made to develop new anticoagulant and antithrombotic drugs. Our previous studies showed that a novel protein, named Fu-P, had fibrinogenolytic activity and much higher fibrinolytic activity on the fibrin plate than urokinase in vitro.

Objective: The antithrombotic activities of Fu-P in vivo are investigated here for the first time.

Materials and methods: Antithrombotic activity of Fu-P was studied in a rat model of artery-vein bypass thrombosis. The anticoagulant activity of Fu-P was measured by clotting assay of activated partial thrombinplastin time and prothrombin time (PT). The effects of Fu-P on the factor Xa and thrombin were assayed using the chromogenic substrate S-2765 and S-2238.

Results: Intravenous injection of Fu-P produced a 58.4% inhibition ratio of thrombus formation at 0.1 mg/kg body weight, while heparin produced 42.5% inhibition ratio of thrombus formation at 0.6 mg/kg body weight. Fu-P significantly prolonged fibrinogen clotting time, activated partial thrombinplastin time and thrombin time, which also prolonged PT. The inhibition assay of the coagulant factors using chromogenic substrates S-2238 and S-2765 showed that Fu-P was not the inhibitor of the thrombin and Xa.

Discussion and conclusion: These findings demonstrated that the novel fibrinolytic enzyme (Fu-P) might also be used as a natural agent for thrombolytic therapy or thrombosis prevention.

Keywords::

• Fibrinogenolytic activity
• S-2238
• S-2765
• anticoagulant

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