Programa de Pós-Graduação em Biologia Marinha, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
Biomed Res Int. 2013;2013:294289. doi: 10.1155/2013/294289. Epub 2013 Apr 22.
Snake venoms are complex mixtures of proteins of both enzymes and nonenzymes, which are responsible for producing several biological effects. Human envenomation by snake bites particularly those of the viperid family induces a complex pathophysiological picture characterized by spectacular changes in hemostasis and frequently hemorrhage is also seen. The present work reports the ability of six of a series of 1,2,3-triazole derivatives to inhibit some pharmacological effects caused by the venoms of Bothrops jararaca and Lachesis muta. In vitro assays showed that these compounds were impaired in a concentration-dependent manner, the fibrinogen or plasma clotting, hemolysis, and proteolysis produced by both venoms. Moreover, these compounds inhibited biological effects in vivo as well. Mice treated with these compounds were fully protected from hemorrhagic lesions caused by such venoms. But, only the B. jararaca edema-inducing activity was neutralized by the triazoles. So the inhibitory effect of triazoles derivatives against some in vitro and in vivo biological assays of snake venoms points to promising aspects that may indicate them as molecular models to improve the production of effective antivenom or to complement antivenom neutralization, especially the local pathological effects, which are partially neutralized by antivenoms.
蛇毒是由酶和非酶蛋白质组成的复杂混合物,这些蛋白质负责产生多种生物学效应。人类被蛇咬伤,特别是被蝰蛇科咬伤,会引起复杂的病理生理现象,表现为止血功能明显改变,常伴有出血。本研究报告了一系列 1,2,3-三唑衍生物中的六种抑制 Bothrops jararaca 和 Lachesis muta 毒液引起的一些药理学作用的能力。体外试验表明,这些化合物以浓度依赖的方式抑制两种毒液引起的纤维蛋白原或血浆凝固、溶血和蛋白水解。此外,这些化合物还抑制了体内的生物学效应。用这些化合物处理的小鼠完全免受这些毒液引起的出血性损伤。但是,只有三唑类化合物能中和 B. jararaca 诱导的水肿活性。因此,三唑衍生物对蛇毒的一些体外和体内生物学检测的抑制作用表明了它们具有很大的应用前景,它们可能是改善有效抗蛇毒血清生产或补充抗蛇毒血清中和作用的分子模型,特别是局部病理作用,抗蛇毒血清部分中和了这种作用。