Terreros Myriam Janeth Salazar, de Luna Luis Augusto Visani, Giorgio Selma
Department of Animal Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
Department of Animal Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil; Laboratory of Solid State Chemistry, Institute of Chemistry, State University of Campinas, Campinas, São Paulo, Brazil.
Parasitol Int. 2019 Aug;71:163-166. doi: 10.1016/j.parint.2019.04.011. Epub 2019 Apr 13.
Leishmaniasis is a poverty-related disease, the chemotherapy of which is based on few drugs. The in vitro macrophage-amastigote model using mouse peritoneal cells, human-monocyte transformed macrophages and immortalized cell lines have been used to test new and safe antileishmanial drugs. Considering the differences for drug sensitivities between these Leishmania infected cells, the efficacy of amphotericin B, pentavalent antimonial, miltefosine and resveratrol was evaluated in a recently developed ex vivo culture of macrophages isolated from mouse lesion induced by L. amazonensis (CD11bF4/80CD68CD14) compared with infected peritoneal macrophages (CD11bF4/80CD68CD14). The results show that IC50 values of amphotericin B, miltefosine and pentavalent antimonial for parasites in lesional and peritoneal macrophages were similar, although high doses of these compounds did not result in total clearance of parasites in lesional cells (amphotericin B), peritoneal cells (miltefosine) and both cell cultures (pentavalent antimonial). Amastigotes infecting lesional macrophages were more resistant to resveratrol as compared to parasites in peritoneal macrophages. The cytoxicity of miltefosine and resveratrol was higher in infected peritoneal macrophages than in lesional cells. These data suggest that the antileishmanial effect and citotoxicity of some anti leishmanial compounds are dependent of macrophage source and mouse peritoneal macrophages loaded with amastigotes do not represent the lesion cell.
利什曼病是一种与贫困相关的疾病，其化疗基于少数几种药物。使用小鼠腹腔细胞、人单核细胞转化巨噬细胞和永生化细胞系的体外巨噬细胞-无鞭毛体模型已被用于测试新型安全的抗利什曼药物。考虑到这些感染利什曼原虫的细胞之间药物敏感性的差异，与感染的腹腔巨噬细胞（CD11bF4/80CD68CD14）相比，在最近开发的从亚马逊利什曼原虫诱导的小鼠病变中分离的巨噬细胞（CD11bF4/80CD68CD14）的体外培养中评估了两性霉素B、五价锑、米替福新和白藜芦醇的疗效。结果表明，两性霉素B、米替福新和五价锑对病变巨噬细胞和腹腔巨噬细胞中寄生虫的IC50值相似，尽管高剂量的这些化合物并未导致病变细胞（两性霉素B）、腹腔细胞（米替福新）和两种细胞培养物（五价锑）中的寄生虫被完全清除。与腹腔巨噬细胞中的寄生虫相比，感染病变巨噬细胞的无鞭毛体对白藜芦醇更具抗性。米替福新和白藜芦醇在感染的腹腔巨噬细胞中的细胞毒性高于病变细胞。这些数据表明，一些抗利什曼化合物的抗利什曼作用和细胞毒性取决于巨噬细胞来源，并且负载有无鞭毛体的小鼠腹腔巨噬细胞并不代表病变细胞。
