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Treatment with melatonin induces a reduction of Toxoplasma gondii development in LLC-MK2 cells.
Parasitology Research ( IF 1.8 ) Pub Date : 2020-06-14 , DOI: 10.1007/s00436-020-06766-5
Nayara Inocencio Machado 1, 2 , Thiago Alves Teixeira Dos Santos 1, 2, 3 , Wanderley de Souza 4 , Renato Augusto DaMatta 2 , Sergio Henrique Seabra 1, 2
Affiliation  

It is known that the current treatment for toxoplasmosis causes side effects. Thus, it is essential to develop new therapies with reduced adverse effects while concurrently maintaining broad coverage and prophylactic therapy. Melatonin is a hormone that participates in the circadian cycle in vertebrates and has antioxidant, immunomodulatory, and antitumoral functions. In addition, it has been shown that melatonin can modulate immune responses and parasitic development during infection by Trypanosoma cruzi and Leishmania spp. Furthermore, studies indicate that melatonin increases the number of lymphocytes in rats infected by Toxoplasma gondii. However, there is no information on the possible effects of melatonin in T. gondii-infected host cells in vitro. This study analyzed the effects of melatonin treatment in the monkey kidney cell epithelial cell line, LLC-MK2, after infection with T. gondii. LLC-MK2 cells were infected and treated/not treated with melatonin, and the infection index was then quantified. Melatonin treatment did not alter host cell viability and was able to reduce parasite proliferation in LLC-MK2 cells at 24 and 48 h and at 6 days. Analysis by scanning electron microscopy confirmed reduction of parasite proliferation and alterations of tachyzoite shapes. Transmission electron microscopy images showed parasites with ruptured plasma membranes and cytoplasmic leakage. After treatment, parasites showed positive staining for apoptotic-like cell death. These results suggest that the use of melatonin as the lead compound for the synthesis of new compounds may constitute an alternative treatment for toxoplasmosis.



中文翻译:

褪黑素的治疗诱导LLC-MK2细胞中弓形虫的发育减少。

已知当前的弓形虫病治疗会引起副作用。因此,重要的是要开发新的疗法以减少不良反应,同时保持广泛的覆盖范围和预防性疗法。褪黑激素是一种参与脊椎动物昼夜节律的激素,具有抗氧化,免疫调节和抗肿瘤功能。另外,已经表明褪黑激素可以在克鲁氏锥虫利什曼原虫属的感染期间调节免疫应答和寄生虫的发展。此外,研究表明褪黑激素会增加弓形虫感染大鼠的淋巴细胞数量。但是,尚无关于褪黑激素可能对弓形虫的影响的信息体外感染宿主细胞。这项研究分析了褪黑素治疗对刚地弓形虫感染后猴肾细胞上皮细胞系LLC-MK2的影响将LLC-MK2细胞感染并用褪黑素处理/不进行处理,然后量化感染指数。褪黑素处理不会改变宿主细胞的活力,并且能够在24、48小时和6天时减少LLC-MK2细胞中的寄生虫增殖。通过扫描电子显微镜的分析证实了寄生虫增殖的减少和速殖子形状的改变。透射电子显微镜图像显示寄生虫具有质膜破裂和细胞质泄漏。治疗后,寄生虫显示出凋亡样细胞死亡的阳性染色。这些结果表明,将褪黑激素用作合成新化合物的先导化合物可能构成弓形虫病的另一种治疗方法。

更新日期:2020-06-14
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