Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Nanomaterials Group, Department of Materials Engineering, Tarbiat Modares University, Tehran, Iran.
J Trace Elem Med Biol. 2019 Dec;56:162-168. doi: 10.1016/j.jtemb.2019.08.003. Epub 2019 Aug 13.
The pentavalent antimonial compounds are the first drug of choice for leishmania infection, but have several side effects that cause some restriction for use. Extension of nanoparticle use in biological research and proven effectiveness of manganese nanoparticles on fungi and bacteria, along with the lack of information about its antileishmanial effects, have motivated this study. Manganese can induce cell apoptosis by increasing FOXO3a-Bim/PUMA mRNA activation and activating of caspase-3 pathway.
This study was aimed to examine the efficacy of manganese oxide nanoparticles againstLeishmania major (MRHO/IR/75/ER) in vitro and in vivo. To evaluate the antileishmanial activity of NPs, light microscopic observation was used to determine the number of remaining parasites in each well. The MTT test was used to determine the cytotoxicity effects of MnO NPs against L. major promastigotes and macrophage cells. The effect of nanoparticles on cultured amastigotes under in vitro conditions was also investigated. The possible apoptosis of L. major by MnO NPs was evaluated with flow cytometry assay. Additionally, the preventive and therapeutic effects of MnO NPs in BALB/c mice following cutaneous L. major infection was tested. The effect of MnO NPs on promastigotes and amastigotes were proven by MTT assay and amastigote assay, respectively.
The IC value of MnO NPs against L. major promastigotes and macrophages was 15 and 40 μg ml respectively. The results of flow cytometry showed about 57% of the promastigotes were induced to apoptosis with MnO NPs. In in vivo studies, the size of the ulcers were significantly reduced, and the survival rate of the mice, in comparison with the control group, was increased.
MnO NPs has a beneficial effect on L. major promastigotes in vitro and in vivo and could be considered as a candidate for the treatment of this infection.
五价锑化合物是治疗利什曼原虫感染的首选药物之一，但具有一些副作用，导致其使用受到一定限制。纳米粒子在生物研究中的应用不断扩展，并且锰纳米粒子对真菌和细菌的有效性已得到证实，同时缺乏其抗利什曼原虫作用的信息，这促使我们进行了这项研究。锰可以通过增加 FOXO3a-Bim/PUMA mRNA 的激活和激活 caspase-3 途径来诱导细胞凋亡。
本研究旨在体外和体内评估氧化锰纳米粒子对利什曼原虫（MRHO/IR/75/ER）的疗效。为了评估 NPs 的抗利什曼原虫活性，通过光显微镜观察确定每个孔中剩余寄生虫的数量。MTT 试验用于确定 MnO NPs 对利什曼原虫前鞭毛体和巨噬细胞的细胞毒性作用。还研究了纳米粒子对体外培养的无鞭毛体的影响。通过流式细胞术评估 MnO NPs 对利什曼原虫的可能凋亡作用。此外，还测试了 MnO NPs 在 BALB/c 小鼠皮肤感染利什曼原虫后的预防和治疗效果。MTT 试验和无鞭毛体试验分别证明了 MnO NPs 对前鞭毛体和无鞭毛体的作用。
MnO NPs 对利什曼原虫前鞭毛体和巨噬细胞的 IC 值分别为 15 和 40μg ml。流式细胞术结果显示，约 57%的前鞭毛体被 MnO NPs 诱导凋亡。在体内研究中，与对照组相比，溃疡的大小明显减小，小鼠的存活率增加。
MnO NPs 对利什曼原虫前鞭毛体具有有益的体外和体内作用，可考虑作为治疗这种感染的候选药物。
