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

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.