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

Autor(es)

Jacob-Ferreira, Anna L. ; Menaldo, Danilo L. ; Sartim, Marco A. ; Riul, Thalita B. ; Dias-Baruffi, Marcelo ; Sampaio, Suely V.

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 95, p. 263-267, FEB 2017.
• Citações Web of Science: 7

Resumo

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 5 min), 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 (12 mg/kg) reduced thrombus formation in 81%, similarly to heparin (100 U/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. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/21569-9 - ATIVIDADES ANTITROMBÓTICAS E TROMBOLÍTICAS DA BATROXASE, UMA METALOPROTEASE PURIFICADA DO VENENO DA COBRA Bothrops atrox, EM MODELOS EXPERIMENTAIS ANIMAIS.
• Beneficiário: Anna Laura Bechara Jacob Ferreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado