Jacob-Ferreira Anna L, Menaldo Danilo L, Sartim Marco A, Riul Thalita B, Dias-Baruffi Marcelo, Sampaio Suely V
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.
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.
Int J Biol Macromol. 2017 Feb;95:263-267. doi: 10.1016/j.ijbiomac.2016.11.063. Epub 2016 Nov 19.
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.
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.
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.
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.
Batroxase presents antithrombotic activity in vivo. Moreover, its lack of immunogenicity increases the interest on its possible therapeutic potential over thrombogenic disorders.
蛇毒是生物活性分子的重要来源，可作为新药的模型。多年来，干扰止血的毒素受到了广泛关注。
本研究旨在评估矛头蝮蛇毒中的一种P-I金属蛋白酶——巴曲酶在静脉血栓形成动物模型中的抗血栓活性。
与肝素钠（阳性对照）和生理盐水（阴性对照）相比，在基于维氏三要素中两个因素的模型中对巴曲酶的抗血栓活性进行体内测试：血流改变（下腔静脉部分狭窄）和血管壁损伤（10%氯化铁处理5分钟）。通过尾部出血试验评估出血/凝血时间。还分析了巴曲酶的免疫原性。
巴曲酶（12mg/kg）使血栓形成减少了81%，与肝素（100U/kg）相似，肝素使血栓形成减少了85%（与生理盐水组相比）。巴曲酶和肝素均使出血/凝血时间增加了约3倍。用巴曲酶免疫兔子未检测到针对这种金属蛋白酶的抗体水平。
巴曲酶在体内具有抗血栓活性。此外，其缺乏免疫原性增加了人们对其治疗血栓形成性疾病潜在可能性的兴趣。
