Further characterization and thrombolytic activity in a rat model of a fibrinogenase from Vipera lebetina venom.
Vipera lebetina fibrinogenase (VlF) was shown to render fibrinogen incoagulable and to solubilize fibrin. The fibrinogenolytic activity of this enzyme was found to be 33 mg fibrinogen/min/mg protein. The study of the specificity of this enzyme revealed that it has no effect on purified factor X, prothrombin and protein C and on the specific chromogenic substrates of their active form. Plasminogen was not activated by VlF but slightly degraded. We have also compared the effect of VlF and plasmin on fibrinogen and shown that these two enzymes have a different sites of cleavage. This enzyme inhibited human platelet aggregation on PRP initiated by ADP and collagen but was without effect on the aggregation of washed rabbit platelets using thrombin as agonist. Administration of VlF in rat did not show any necrosis or hemorrhage in treated rats organ's. We therefore, examined the thrombolytic activity of VlF in a rat model of venous thrombosis. Thrombus was produced in the posterior vena cava by injection of human fibrinogen and thrombin. Injection of 5 mg/Kg body weight showed an evident flow restoration after one hour and measurement of the fibrinogen level a decrease of about 30% after 3 hrs. VlF's action is not dependent on plasminogen activators and may act synergistically with them, thereby providing an intriguing potential clinical application for dissolution of blood clots.
Gasmi
A
A
Laboratoire venins et toxines, Institut Pasteur de Tunis, Tunisia.
Chabchoub
A
A
Guermazi
S
S
Karoui
H
H
Elayeb
M
M
Dellagi
K
K
D000818:Animals; D004195:Disease Models, Animal; D005170:Factor X / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000494:pharmacology*; D010958:Plasminogen / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D011817:Rabbits; D011859:Radiography; D051381:Rats; D013924:Thrombophlebitis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D014757:Viper Venoms / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D011486:Protein C; D014757:Viper Venoms; D011516:Prothrombin; D005170:Factor X; D005340:Fibrinogen; D010958:Plasminogen; D005341:Fibrinolysin; D008666:Metalloendopeptidases