Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, UFU, Uberlândia, MG, Brazil.
Parasitology. 2013 Jun;140(7):844-54. doi: 10.1017/S0031182013000012. Epub 2013 Feb 27.
This paper reports the effects of BnSP-7 toxin, a catalytically inactive phospholipase A2 from Bothrops pauloensis snake venom, on Leishmania (Leishmania) amazonensis. BnSP-7 presented activity against promastigote parasite forms both in the MTT assay, with IC50 of 58.7 μg mL(-1) of toxin, and a growth curve, inhibiting parasite proliferation 60-70% at concentrations of 50-200 μg mL(-1) of toxin 96 h after treatment. Also, the toxin presented effects on amastigotes, reducing parasite viability by 50% at 28.1 μg mL(-1) and delaying the amastigote-promastigote differentiation process. Ultrastructural studies showed that BnSP-7 caused severe morphological changes in promastigotes such as mitochondrial swelling, nuclear alteration, vacuolization, acidocalcisomes, multiflagellar aspects and a blebbing effect in the plasma membrane. Finally, BnSP-7 interfered with the infective capacity of promastigotes in murine peritoneal macrophages, causing statistically significant infectivity-index reductions (P < 0.05) of 20-35%. These data suggest that the BnSP-7 toxin is an important tool for the discovery of new parasite targets that can be exploited to develop new drugs for treating leishmaniasis.
本文报道了来自巴西矛头蝮蛇毒液的无催化活性磷脂酶 A2(BnSP-7 毒素)对亚马逊利什曼原虫的影响。BnSP-7 对前鞭毛体寄生虫形式均具有活性,在 MTT 测定中,IC50 为 58.7μg mL(-1)的毒素,并且在生长曲线中,在 50-200μg mL(-1)的毒素浓度下处理 96 小时后,抑制寄生虫增殖 60-70%。此外,该毒素对无鞭毛体也有作用,在 28.1μg mL(-1)时使寄生虫活力降低 50%,并延迟无鞭毛体-前鞭毛体分化过程。超微结构研究表明,BnSP-7 导致前鞭毛体发生严重的形态变化,如线粒体肿胀、核改变、空泡化、酸钙体、多鞭毛体和质膜起泡效应。最后,BnSP-7 干扰了前鞭毛体在鼠腹腔巨噬细胞中的感染能力,导致感染指数显著降低(P < 0.05),为 20-35%。这些数据表明,BnSP-7 毒素是发现新的寄生虫靶标和开发治疗利什曼病新药的重要工具。