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铂类化合物奥沙利铂的抗利什曼原虫活性

and Antileishmanial Activity of a Compound Derived of Platinum, Oxaliplatin, against .

作者信息

Ghasemi Ezatollah, Ghaffarifar Fatemeh, Dalimi Abdolhossein, Sadraei Javid

机构信息

Department of Parasitology and Entomology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Iran J Pharm Res. 2019 Fall;18(4):2028-2041. doi: 10.22037/ijpr.2019.15364.13046.

Abstract

This study aimed to evaluate the antileishmanial efficacy of oxaliplatin against both and . The IC, CC, and SI of oxaliplatin against promastigotes, murine macrophages, Raw 264.7 cells, and intramacrophage amastigotes of were investigated . The effects of this drug on intracellular amastigotes were also assayed, and the percentage of infectivity and IIR were calculated. Flow cytometry was performed to assay apoptosis, using 50 and 100 µg/mL of oxaliplatin in the promastigotes and macrophages. , the BALB/c mice were classified into three groups, receiving oxaliplatin, glucantime, and phosphate-buffered saline for one month, respectively. The lesion size, IFN-γ, and IL-4 levels, and parasite burden were also evaluated in the animals. After 72 h, the IC and CC of oxaliplatin against promastigotes and macrophages were respectively 0.5 and 66.78 µg/mL. The apoptosis of promastigotes and macrophages using 50 µg/mL of oxaliplatin was 7.25% and 2.14%, respectively, while apoptosis induced at 100 µg/mL was 15.48% and 2.80%, respectively. Similar to the glucantime group, the mice treated with oxaliplatin showed a lower parasite burden and smaller lesions, compared with the PBS group ( 0.01). Furthermore, higher IFN-γ levels were reported in mice receiving oxaliplatin in comparison with those receiving PBS ( 0.01). The current findings indicated the efficacy of oxaliplatin against promastigote and amastigote forms of and induced leishmaniasis.

摘要

本研究旨在评估奥沙利铂对[具体两种情况未明确]的抗利什曼原虫疗效。研究了奥沙利铂对前鞭毛体、小鼠巨噬细胞、Raw 264.7细胞以及[具体寄生虫未明确]的巨噬细胞内无鞭毛体的半数抑制浓度(IC)、半数细胞毒性浓度(CC)和选择性指数(SI)。还测定了该药物对细胞内无鞭毛体的影响,并计算了感染率和抑制指数(IIR)。使用50和100μg/mL的奥沙利铂处理前鞭毛体和巨噬细胞后,通过流式细胞术检测细胞凋亡情况。此外[此处原文逻辑不连贯,推测可能有信息缺失],将BALB/c小鼠分为三组,分别接受奥沙利铂、葡糖胺锑钠和磷酸盐缓冲盐水治疗一个月。还评估了动物的病变大小、干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)水平以及寄生虫负荷。72小时后,奥沙利铂对前鞭毛体和巨噬细胞的IC分别为0.5和66.78μg/mL。使用50μg/mL奥沙利铂时,前鞭毛体和巨噬细胞的凋亡率分别为7.25%和2.14%,而使用100μg/mL时诱导的凋亡率分别为15.48%和2.80%。与葡糖胺锑钠组相似,与磷酸盐缓冲盐水(PBS)组相比,接受奥沙利铂治疗的小鼠寄生虫负荷更低且病变更小(P<0.01)。此外,与接受PBS的小鼠相比,接受奥沙利铂的小鼠报告的IFN-γ水平更高(P<0.01)。目前的研究结果表明奥沙利铂对[具体寄生虫未明确]的前鞭毛体和无鞭毛体形式以及诱导的利什曼病具有疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d8a/7059061/82f455312254/ijpr-18-2028-g001.jpg

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