Immunotoxicology Research Group, Pharmacy Department, Science Faculty, Universidad Nacional de Colombia, Oficina 206, Ciudad Universitaria, Carrera 30 No. 45-03, Edificio 450, Bogotá, D.C., Colombia.
Biomed Pharmacother. 2011 Dec;65(8):569-77. doi: 10.1016/j.biopha.2010.12.016. Epub 2011 Jun 23.
Among the problems associated to leishmaniasis, the two most outstanding ones are the lack of a vaccine and the adverse effects caused by drugs use for its control. Meglumine antimoniate compounds are the first-line drugs in the treatment for cutaneous leishmaniasis (the most prevalent form of the disease in Colombia); nevertheless, they are far from being ideal drugs due to their toxicity (not to mention the emergence of drug-resistant parasites), all of which has prompted current search for new strategies to improve their safety. This work assesses the effectiveness and safety (toxicity including new aspects related with immunotoxicity not reported previously) of two different meglumine antimoniate formulations using an in vitro and in vivo murine model. The results evidence that although both injectable formulations induce an equally efficient (clearance of intracellular parasites), both give rise to adverse effects, including a preferential immunomodulation on Balb/c mice and in a lesser proportion on ICR mice. These results are comparable to human trials reporting variable reactions when following the same treatment regimen. The model presented herein is proposed as a tool for evaluating the effectiveness and safety of meglumine antimoniate-based antileishmanial formulations.
在与利什曼病相关的问题中，两个最突出的问题是缺乏疫苗和控制该病所用药物的副作用。葡甲胺锑酸盐化合物是治疗皮肤利什曼病（哥伦比亚最常见的疾病形式）的一线药物；然而，由于其毒性（更不用说抗药性寄生虫的出现），它们远非理想药物，这促使人们目前正在寻找新的策略来提高它们的安全性。本工作使用体外和体内小鼠模型评估了两种不同葡甲胺锑酸盐制剂的有效性和安全性（毒性，包括以前未报道过的与免疫毒性相关的新方面）。结果表明，尽管两种注射制剂都能产生同样有效的效果（清除细胞内寄生虫），但它们都会引起不良反应，包括对 Balb/c 小鼠的免疫调节作用更明显，而对 ICR 小鼠的作用则较小。这些结果与报告采用相同治疗方案时出现不同反应的人类试验结果相当。本文提出的模型可作为评估基于葡甲胺锑酸盐的抗利什曼病制剂的有效性和安全性的工具。
