Departamento de Parasitologia, Microbiologia e Imunologia, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais, 36036-900, Brazil.
Departamento de Química, I.C.E., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais, 36036-900, Brazil.
Exp Parasitol. 2018 Dec;195:78-86. doi: 10.1016/j.exppara.2018.10.007. Epub 2018 Oct 29.
Currently, available treatment options for leishmaniasis are limited and unsatisfactory. In a previous study, a quinoline derivative (AMQ-j), exhibited a strong effect against Leishmania amazonensis and its antileishmanial activity was preliminarily associated with mitochondrial dysfunction. The present study further explores the antileishmanial effect of this compound against L. amazonensis, as well as determines the main cellular processes involved in the death of the parasite. Moreover, this study evaluated the in vivo effect of the AMQ-j in BALB/c mice experimentally infected by L. amazonensis. The results showed that the compound AMQ-j induces a set of morphological and biochemical features that could correlate with both autophagy-related and apoptosis-like processes, indicating intense mitochondrial swelling, a collapse of the mitochondrial membrane potential, an abnormal chromatin condensation, an externalization of phosphatidylserine, an accumulation of lipid bodies, a disorganization of cell cycle, a formation of autophagic vacuoles, and an increase of acidic compartments. Treatment with AMQ-j through an intralesional route was effective in reducing the parasite burden and size of the lesion. No significant increase in the serum levels of hepatic or renal damage toxicity markers was observed. These findings contribute to the understanding of the mode of action of quinoline derivatives involved in the death of Leishmania parasites and encourage new studies in other experimental models of Leishmania infection.
目前，针对利什曼病的治疗选择有限且不尽如人意。在之前的一项研究中，一种喹啉衍生物（AMQ-j）对亚马逊利什曼原虫表现出强大的作用，其抗利什曼活性初步与线粒体功能障碍有关。本研究进一步探讨了该化合物对亚马逊利什曼原虫的抗利什曼作用，并确定了参与寄生虫死亡的主要细胞过程。此外，本研究还评估了 AMQ-j 在 BALB/c 小鼠体内对感染亚马逊利什曼原虫的实验中的体内作用。结果表明，该化合物 AMQ-j 诱导了一系列形态和生化特征，这些特征可能与自噬相关和凋亡样过程相关，表明线粒体肿胀强烈、线粒体膜电位崩溃、染色质异常浓缩、磷脂酰丝氨酸外排、脂滴积累、细胞周期紊乱、自噬泡形成和酸性区室增加。通过瘤内途径用 AMQ-j 治疗可有效降低寄生虫负荷和病变大小。未观察到肝或肾损伤毒性标志物血清水平显著增加。这些发现有助于理解参与利什曼原虫死亡的喹啉衍生物的作用模式，并鼓励在其他利什曼虫感染实验模型中进行新的研究。
