Tavares Grasiele S V, Mendonça Débora V C, Miyazaki Carolina K, Lage Daniela P, Soyer Tauane G, Carvalho Lívia M, Ottoni Flaviano M, Dias Daniel S, Ribeiro Patrícia A F, Antinarelli Luciana M R, Ludolf Fernanda, Duarte Mariana C, Coimbra Elaine S, Chávez-Fumagalli Miguel A, Roatt Bruno M, Menezes-Souza Daniel, Barichello José Mário, Alves Ricardo J, Coelho Eduardo A F
Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil.
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.
Parasitol Int. 2019 Feb;68(1):63-72. doi: 10.1016/j.parint.2018.10.005. Epub 2018 Oct 16.
Clioquinol (5-chloro-7-iodoquinolin-8-ol or ICHQ) was recently showed to presents an in vitro effective antileishmanial action, causing changes in membrane permeability, mitochondrial functionality, and parasite morphology. In the present study, ICHQ was incorporated into a Poloxamer 407-based polymeric micelles system (ICHQ/M), and its antileishmanial activity was in vivo evaluated in L. amazonensis-infected BALB/c mice. Amphotericin B (AmpB) and its liposomal formulation (Ambisome®) were used as controls. Parasitological and immunological evaluations were performed 30 days after the treatment. Results indicated more significant reductions in the average lesion diameter and parasite burden in ICHQ or ICHQ/M-treated mice, which were associated with the development of a polarized Th1 immune response, based on production of high levels of IFN-γ, IL-12, TNF-α, GM-CSF, and antileishmanial IgG2a antibody. Control groups´ mice produced high levels of IL-4, IL-10, and IgG1 isotype antibody. No organic toxicity was found by using ICHQ or ICHQ/M to treat the animals, although those receiving AmpB and Ambisome® have presented higher levels of renal and hepatic damage markers. In conclusion, results suggested that the ICHQ/M composition can be considered as an antileishmanial candidate to be tested against human leishmaniasis.
氯碘羟喹(5-氯-7-碘喹啉-8-醇或ICHQ)最近被证明具有体外抗利什曼原虫活性,可引起膜通透性、线粒体功能和寄生虫形态的变化。在本研究中,ICHQ被载入基于泊洛沙姆407的聚合物胶束系统(ICHQ/M),并在感染亚马逊利什曼原虫的BALB/c小鼠体内评估其抗利什曼原虫活性。两性霉素B(AmpB)及其脂质体制剂(安必素®)用作对照。治疗30天后进行寄生虫学和免疫学评估。结果表明,ICHQ或ICHQ/M治疗的小鼠平均病变直径和寄生虫负荷显著降低,这与基于高水平IFN-γ、IL-12、TNF-α、GM-CSF和抗利什曼原虫IgG2a抗体产生的极化Th1免疫反应的发展有关。对照组小鼠产生高水平的IL-4、IL-10和IgG-1同种型抗体。使用ICHQ或ICHQ/M治疗动物未发现器官毒性,尽管接受AmpB和安必素®的动物呈现出更高水平的肾和肝损伤标志物。总之,结果表明ICHQ/M组合物可被视为一种抗利什曼原虫候选物,用于测试治疗人类利什曼病。