Synergistic Anti-Leishmanial Activities of Morphine and Imiquimod on Leishmania infantum (MCAN/ES/98/LIM-877).

IF 0.6 4区医学 Q4 PARASITOLOGY

Journal of Arthropod-Borne Diseases Pub Date : 2021-06-30 eCollection Date: 2021-06-01 DOI:10.18502/jad.v15i2.7492

Fatemeh Ghaffarifar, Masoud Foroutan, Soheila Molaei, Eslam Moradi-Asl

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引用次数: 1

Abstract

Background: This study was performed to evaluate in vitro and in vivo Leishmanicidal potential of morphine (Mph), imiquimod (IQ), and their combination.

Methods: Leishmania infantum promastigote and amastigote assays were performed at the presence of 0.015-150μM Mph, 0.04-416μM IQ, and their combination. The inhibition effects of these drugs on promastigotes were evaluated after 24, 48, and 72h. The cytotoxic effects of the drugs were evaluated by MTT as well as flow cytometry after 72h. We explored the therapeutic effects of Mph and IQ in BALB/c mice at the end of the treatment using parasite load determination and cytokine assay. One group of mice received Mph for three weeks before infection.

Results: The results of promastigote and amastigote assays showed the cytotoxic effects of the drugs at low concentrations. The cytotoxic effects were higher on promastigotes than amastigotes (p< 0.05). There was a negative correlation between drug concentration and amastigote/promastigote viability. Imiquimod alone or combined with Mph showed remarkable cytotoxic effects at all concentrations (p< 0.05). Flow cytometry results revealed apoptosis in the parasite following exposure to the drug combinations. Accordingly, the reduction of parasite loads in the spleen and liver was observed (p< 0.05) with simultaneous increases in IFN-γ and IL-4. We believe that the in vivo leishmanicidal effect was mediated by Mph through IL-4 and by IQ through both IL-4 and IFN-γ.

Conclusion: Results pointed out the promising effects of Mph and IQ at low concentrations, especially when combined.

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吗啡和咪喹莫特对幼年利什曼原虫的协同抗利什曼原虫活性研究(MCAN/ES/98/ limm -877)。

背景:本研究旨在评价吗啡(Mph)、咪喹莫特(IQ)及其联合用药的体外和体内杀灭利什曼尼的潜能。方法:在0.015 ~ 150μ m Mph、0.04 ~ 416μ m IQ及两者组合条件下，对婴儿利什曼原虫原鞭毛菌和无尾鞭毛菌进行检测。分别在24、48、72h后观察药物对原鞭毛菌的抑制作用。72h后采用MTT和流式细胞术评价药物的细胞毒作用。我们通过寄生虫负荷测定和细胞因子测定，探讨了治疗结束时BALB/c小鼠的Mph和IQ的治疗效果。一组小鼠在感染前接受三周的Mph治疗。结果:在低浓度条件下，promastigote和amastigote检测结果显示出药物的细胞毒作用。对promastigotes的细胞毒作用高于amastigotes (p< 0.05)。药物浓度与无马鞭毛菌/原马鞭毛菌活力呈负相关。咪喹莫特单用或联用Mph均有显著的细胞毒作用(p< 0.05)。流式细胞术结果显示，暴露于药物组合后，寄生虫发生凋亡。由此可见，脾脏和肝脏中寄生虫负荷减少(p< 0.05)， IFN-γ和IL-4同时升高。我们认为，体内利什曼尼效应是由Mph通过IL-4介导的，而IQ通过IL-4和IFN-γ介导的。结论:研究结果表明，在低浓度下，Mph和IQ具有良好的效果，特别是当两者结合使用时。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Arthropod-Borne Diseases PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH-PARASITOLOGY

CiteScore

2.00

自引率

11.10%

发文量

审稿时长

8 weeks

期刊介绍： The journal publishes original research paper, short communication, scientific note, case report, letter to the editor, and review article in English. The scope of papers comprises all aspects of arthropod borne diseases including: ● Systematics ● Vector ecology ● Epidemiology ● Immunology ● Parasitology ● Molecular biology ● Genetics ● Population dynamics ● Toxicology ● Vector control ● Diagnosis and treatment and other related subjects.