ANTITHROMBOTIC AND TROMBOLYTIC ACTIVITIES OF BATROXASE, A METALLOPROTEINASE PURIFIED FROM THE VENOM OF Bothrops atrox SNAKE, IN EXPERIMENTAL ANIMAL MODELS.

• Grant number: 12/21569-9
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2013
• Effective date (End): February 28, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Suely Vilela
• Grantee: Anna Laura Bechara Jacob Ferreira
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis, AP.TEM

Abstract

Animal venoms are constituted by a variety of substances with toxic effects, which may act either isolated or in synergy, causing different types of damage to the victim or pray. To study chemical and functional characteristics of the isolated toxins is interesting not only due to its relevance in the poisoning, but also due to its potential as a source of bioactive molecules that can be used as a model of new drugs for the treatment of different pathological processes. Due to the importance of blood coagulation and platelet aggregation in cardiovascular and cerebrovascular diseases, snake venom proteins, which interfere in these processes, have received considerable attention in recent years. Batroxase, which is a metalloproteinase isolated from Bothrops atrox (Pará) snake venom, was recently purified and biochemically characterized in our laboratory. Batroxase showed antithrombotic and thrombolytic activity in vitro, as it is capable to proteolyse components of the coagulation cascade, as fibrinogen and fibrin. In this project we aim at investigate batroxase's activity to the hemostasis of rats, analysing its thrombolytic and antithrombotic activity, in comparison with clinically relevant drugs like tPA and heparin, respectively, in two thrombosis models: arterial and venous. Nevertheless, we will observe the influence of batroxase over the blood pressure, heart rate, and coagulation measurements of the studied animals. With the beginning of the functional characterization of batroxase, we will be able to initiate exploring the therapeutic potential of this animal toxin for the development and production of new drugs in the future.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MENALDO, DANILO L.; JACOB-FERREIRA, ANNA L.; BERNARDES, CAROLINA P.; CINTRA, ADELIA C. O.; SAMPAIO, SUELY V.. Purification procedure for the isolation of a P-I metalloprotease and an acidic phospholipase A(2) from Bothrops atrox snake venom. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 21, AUG 13 2015. (12/21569-9, 11/23236-4, 12/11963-1)

JACOB-FERREIRA, ANNA L.; MENALDO, DANILO L.; SARTIM, MARCO A.; RIUL, THALITA B.; DIAS-BARUFFI, MARCELO; SAMPAIO, SUELY V.. Antithrombotic activity of Batroxase, a metalloprotease from Bothrops atrox venom, in a model of venous thrombosis. International Journal of Biological Macromolecules, v. 95, p. 263-267, FEB 2017. (11/23236-4, 12/21569-9)

DANILO L. MENALDO; ANNA L. JACOB-FERREIRA; CAROLINA P. BERNARDES; ADÉLIA C. O. CINTRA; SUELY V. SAMPAIO. Purification procedure for the isolation of a P-I metalloprotease and an acidic phospholipase A 2 fromBothrops atrox snake venom. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 21, p. 0-0, 2015-09-29. (12/21569-9, 12/11963-1, 11/23236-4)

JACOB-FERREIRA, ANNA L.; MENALDO, DANILO L.; BERNARDES, CAROLINA P.; SARTIM, MARCO A.; DE ANGELIS, CELIO D.; TANUS-SANTOS, JOSE E.; SAMPAIO, SUELY V.. Evaluation of the in vivo thrombolytic activity of a metalloprotease from Bothrops atrox venom using a model of venous thrombosis. Toxicon, v. 109, p. 18-25, JAN 2016. (11/23236-4, 12/21569-9)