Artículos de revistas
Evaluation Of The In Vivo Thrombolytic Activity Of A Metalloprotease From Bothrops Atrox Venom Using A Model Of Venous Thrombosis
Registro en:
Toxicon. Elsevier Ltd, v. 109, p. 18 - 25, 2016.
410101
10.1016/j.toxicon.2015.11.002
2-s2.0-84947261982
Institución
Resumen
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. © 2015 Elsevier Ltd. All rights reserved. 109
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