Evaluation of the in vivo thrombolytic activity of a metalloprotease from Bothrops atrox venom using a model of venous thrombosis

Autor(es)

Jacob-Ferreira, Anna L. ^{[1, 2]} ; Menaldo, Danilo L. ^[1] ; Bernardes, Carolina P. ^[1] ; Sartim, Marco A. ^[1] ; de Angelis, Celio D. ^[3] ; Tanus-Santos, Jose E. ^[4] ; Sampaio, Suely V. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, FCFRP USP, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Ave Cafe, S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] State Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 109, p. 18-25, JAN 2016.
• Citações Web of Science: 8

Resumo

Background: Due to the importance of blood coagulation and platelet aggregation in brain-and cardiovascular diseases, snake venom proteins that interfere in these processes have received significant attention in recent years considering their potential to be used as models for new drugs. Objectives: This study aimed at the evaluation of the in vivo thrombolytic activity of Batroxase, a P-I metalloprotease from Bothrops atrox venom. Methods: In vivo thrombolytic activity of Batroxase was tested on a model of venous thrombosis in rats, with partial stenosis of the inferior vena cava, and vessel wall injury with ferric chloride at 10% for 5 min. After formation of the thrombus, increasing amounts of Batroxase were administered intravenously. The prescription medication Alteplase (tissue-type plasminogen activator) was used as positive control for thrombolytic activity, while saline was used as negative control. Bleeding time was assessed with a tail bleeding assay. Results: Batroxase presented thrombolytic activity in vivo in a concentration-dependent manner, with 12 mg/kg of the metalloprotease causing a thrombus reduction of 80%, a thrombolytic activity very similar to the one observed for the positive control Alteplase (85%). The tail bleeding time was not altered by the administration of Batroxase, while it increased 3.5 times with Alteplase. Batroxase presented fibrinolytic and fibrinogenolytic activities in vitro, which were inhibited by alpha 2-macroglobulin. Conclusion: Batroxase presents thrombolytic activity in vivo, thus demonstrating a possible therapeutic potential. The inactivation of the metalloprotease by alpha 2-macroglobulin may reduce its activity, but also its potential side effects, as seen for bleeding time. (C) 2015 Elsevier Ltd. 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