Antithrombotic activity of Batroxase, a metalloprotease from Bothrops atrox venom, in a model of venous thrombosis.

ABSTRACT

BACKGROUND: Snake venoms are great sources of bioactive molecules, which may be used as models for new drugs. Toxins that interfere in hemostasis have received considerable attention over the years. OBJECTIVES: This study aimed at the evaluation of the antithrombotic activity of Batroxase, a P-I metalloprotease from Bothrops atrox venom, in an animal model of venous thrombosis. METHODS: The antithrombotic activity of Batroxase was tested in vivo in a model based on two factors of the Virchow's Triad blood flow alterations (partial stenosis of the inferior vena cava), and vessel wall injury (10% ferric chloride for 5min), in comparison with sodium heparin (positive control) and saline (negative control). Bleeding/clotting time was assessed by a tail bleeding assay. The immunogenicity of Batroxase was also analyzed. RESULTS: Batroxase (12mg/kg) reduced thrombus formation in 81%, similarly to heparin (100U/kg), which reduced it in 85% in comparison with the saline group. Both Batroxase and heparin increased bleeding/clotting time in approximately 3 fold. Immunizations of rabbits with Batroxase do not result in detectable levels of antibodies against this metalloprotease. CONCLUSION: Batroxase presents antithrombotic activity in vivo. Moreover, its lack of immunogenicity increases the interest on its possible therapeutic potential over thrombogenic disorders.