Fanti Jacqueline Rodrigues, Tomiotto-Pellissier Fernanda, Miranda-Sapla Milena Menegazzo, Cataneo Allan Henrique Depieri, Andrade Célia Guadalupe Tardeli de Jesus, Panis Carolina, Rodrigues Jean Henrique da Silva, Wowk Pryscilla Fanini, Kuczera Diogo, Costa Idessania Nazareth, Nakamura Celso Vataru, Nakazato Gerson, Durán Nelson, Pavanelli Wander Rogério, Conchon-Costa Ivete
Laboratory of Experimental Protozoology, Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
Laboratory of Experimental Protozoology, Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
Acta Trop. 2018 Feb;178:46-54. doi: 10.1016/j.actatropica.2017.10.027. Epub 2017 Oct 27.
American Cutaneous Leishmaniasis (ACL) is a zoonosis caused by Leishmania protozoa. The ACL chemotherapy available is unsatisfactory motivating researches to seek alternative treatments. In this study, we investigated the action of biogenic silver nanoparticle (AgNp-bio) obtained from Fusarium oxysporium, against Leishmania amazonensis promastigote and amastigote forms. The AgNp-bio promastigote treatment results in promastigote death leading to apoptosis-like events due an increased production of reactive oxygen species (ROS), loss of mitochondrial integrity, phosphatidylserine exposure and damage on promastigotes membrane. In L. amazonensis infected macrophages, AgNp-bio treatment was still able to reduce the percentage of infected macrophages and the amount of amastigotes per macrophage, consequently, the amount of promastigotes recovered. This leishmanicidal effect was also accompanied by a decrease in the levels of ROS and nitric oxide. By observing the ultrastructural integrity of the intracellular amastigotes, we found that the AgNp-bio treatment made a significant damage, suggesting that the compound has a direct effect on intracellular amastigotes. These results demonstrated that AgNp-bio had a direct effect against L. amazonensis forms and acted on immunomodulatory ability of infected macrophages, reducing the infection without inducing the synthesis of inflammatory mediators, which continuous stimulation can generate and aggravate leishmaniotic lesions. Overall, our findings suggest that the use of AgNp-bio stands out as a new therapeutic option to be considered for further in vivo investigations representing a possible treatment for ACL.
美洲皮肤利什曼病（ACL）是由利什曼原虫引起的一种人畜共患病。现有的ACL化疗方法并不理想，这促使人们开展研究以寻找替代治疗方法。在本研究中，我们调查了从尖孢镰刀菌获得的生物源银纳米颗粒（AgNp-bio）对亚马逊利什曼原虫前鞭毛体和无鞭毛体的作用。AgNp-bio对前鞭毛体的处理导致前鞭毛体死亡，并引发类似凋亡的事件，这是由于活性氧（ROS）产生增加、线粒体完整性丧失、磷脂酰丝氨酸暴露以及前鞭毛体膜受损所致。在感染了亚马逊利什曼原虫的巨噬细胞中，AgNp-bio处理仍能够降低被感染巨噬细胞的百分比以及每个巨噬细胞内无鞭毛体的数量，从而减少回收的前鞭毛体数量。这种杀利什曼原虫的作用还伴随着ROS和一氧化氮水平的降低。通过观察细胞内无鞭毛体的超微结构完整性，我们发现AgNp-bio处理造成了显著损伤，这表明该化合物对细胞内无鞭毛体有直接作用。这些结果表明，AgNp-bio对亚马逊利什曼原虫的各形态具有直接作用，并作用于被感染巨噬细胞的免疫调节能力，在不诱导炎症介质合成的情况下减少感染，持续刺激炎症介质会引发并加重利什曼病病变。总体而言，我们的研究结果表明，AgNp-bio作为一种新的治疗选择脱颖而出，值得进一步进行体内研究，有望成为ACL的一种治疗方法。
