title: Antithrombotic activity of Batroxase, a metalloprotease from Bothrops atrox venom, in a model of venous thrombosis.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Batroxase presents antithrombotic activity in vivo. Moreover, its lack of immunogenicity increases the interest on its possible therapeutic potential over thrombogenic disorders.
authors.affiliation: 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.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Jacob-Ferreira
authors.affiliation: 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.
authors.forename: Danilo L
authors.initials: DL
authors.lastname: Menaldo
authors.affiliation: 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.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Sartim
authors.affiliation: 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.
authors.forename: Thalita B
authors.initials: TB
authors.lastname: Riul
authors.affiliation: 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.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Dias-Baruffi
authors.affiliation: 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.
authors.forename: Suely V
authors.initials: SV
authors.lastname: Sampaio
mesh_terms: D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000201:enzymology*; D005343:Fibrinolytic Agents / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects; D008297:Male; D045726:Metalloproteases / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D045726:Metalloproteases
keywords: Antithrombotic agents; Batroxase; Metalloproteases; Snake venom; Venous thrombosis