Anna L Jacob-Ferreira1, Danilo L Menaldo2, Marco A Sartim2, Thalita B Riul2, Marcelo Dias-Baruffi2, Suely V Sampaio3. 1. Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. Electronic address: jacob_ferreira@yahoo.com.br. 2. Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. 3. Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. Electronic address: suvilela@usp.br.
Abstract
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.
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.
Authors: Jacqueline A G Sachett; Iran Mendonça da Silva; Eliane Campos Alves; Sâmella S Oliveira; Vanderson S Sampaio; Fábio Francesconi do Vale; Gustavo Adolfo Sierra Romero; Marcelo Cordeiro Dos Santos; Hedylamar Oliveira Marques; Mônica Colombini; Ana Maria Moura da Silva; Fan Hui Wen; Marcus V G Lacerda; Wuelton M Monteiro; Luiz C L Ferreira Journal: PLoS Negl Trop Dis Date: 2017-07-10
Authors: Wuelton Marcelo Monteiro; Jorge Carlos Contreras-Bernal; Pedro Ferreira Bisneto; Jacqueline Sachett; Iran Mendonça da Silva; Marcus Lacerda; Allyson Guimarães da Costa; Fernando Val; Lisele Brasileiro; Marco Aurélio Sartim; Sâmella Silva-de-Oliveira; Paulo Sérgio Bernarde; Igor L Kaefer; Felipe Gobbi Grazziotin; Fan Hui Wen; Ana Maria Moura-da-Silva Journal: Toxicon X Date: 2020-04-23
Authors: Lynn J Miller; David P Fetterer; Nicole L Garza; Matthew G Lackemeyer; Ginger C Donnelly; Jesse T Steffens; Sean A Van Tongeren; Jimmy O Fiallos; Joshua L Moore; Shannon T Marko; Luis A Lugo-Roman; Greg Fedewa; Joseph L DeRisi; Jens H Kuhn; Scott J Stahl Journal: PLoS One Date: 2018-10-19 Impact factor: 3.240