甲氨蝶呤在皮肤利什曼病治疗中的潜在用途:针对敏感菌株和抗葡甲胺锑酸盐菌株的体外试验

The Potential Use of Methotrexate in the Treatment of Cutaneous Leishmaniasis: In Vitro Assays against Sensitive and Meglumine Antimoniate-resistant Strains of .

作者信息

Mahmoudvand Hossein, Kheirandish Farnaz, Mirbadie Seyed Reza, Kayedi Mohammad Hassan, Rezaei Riabi Tahereh, Ghasemi Abbas Ali, Bamorovat Mehdi, Sharifi Iraj

机构信息

Razi Herbal Medicines Research Center, Dept. of Medical Parasitology and Mycology, Lorestan University of Medical Sciences, Khorramabad, Iran.

Dept. of Medical Parasitology and Mycology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

出版信息

Iran J Parasitol. 2017 Jul-Sep;12(3):339-347.

DOI:
Abstract

BACKGROUND

The present study aimed to evaluate the effect of methotrexate (MTX) alone and in combination with meglumine antimoniate (MA, Glucantime) against sensitive and MA-resistant stages in vitro.

METHODS

The present study was carried out in 2014 in Leishmaniasis Research Center at School of Medicine, Kerman University of Medical sciences, Kerman, Iran. The effects of MTX alone and along with MA on promastigote and amastigote stages of sensitive (SS) and MA-resistant (RS) strains have been evaluated using a colorimetric MTT assay and in a macrophage model, respectively. In addition, the inhibitory effect of MTX on the invasion of murine macrophages was assessed in promastigotes of both strains of . Sensitive and MA resistant are referred to those isolates that are responsive or non-responsive to one or two courses of treatment by MA systemically and/or intralesionally, respectively.

RESULTS

The findings of OD and IC showed that MTX plus MA (SS: 16.1 μg/ml, RS: 39.8 μg/ml) had a higher anti-leishmanial effect than MA (SS: 52.2 μg/ml, RS: 170 μg/ml) or MTX alone (SS: 22.2 μg/ml, RS: 51.4 μg/ml) on promastigotes of both strains of The MTX plus MA caused a significant decrease (0.05) in the mean infection rate (MIR) and the mean number of amastigotes in each macrophage compared with positive control. Infectivity of promastigotes is significantly (0.05) reduced when it was preincubated with MTX.

CONCLUSION

This study indicated high potency and a synergistic effect of MTX on MA in inhibiting the growth rateof promastigote and amastigote stages of sensitive and meglumine antimoniate-resistant . Further works are needed to evaluate the anti-leishmanial effects of MTX on using a clinical setting.

摘要

背景

本研究旨在评估甲氨蝶呤(MTX)单独及与葡甲胺锑酸盐(MA,葡糖胺锑)联合应用对体外敏感及耐MA阶段的影响。

方法

本研究于2014年在伊朗克尔曼医科大学医学院利什曼病研究中心开展。分别采用比色MTT法及巨噬细胞模型评估MTX单独及与MA联合应用对敏感(SS)和耐MA(RS)菌株前鞭毛体和无鞭毛体阶段的影响。此外,在两种菌株的前鞭毛体中评估MTX对小鼠巨噬细胞侵袭的抑制作用。敏感和耐MA分别指那些对MA全身和/或皮损内一或两个疗程治疗有反应或无反应的分离株。

结果

OD和IC结果显示,MTX加MA(SS:16.1μg/ml,RS:39.8μg/ml)对两种菌株前鞭毛体的抗利什曼原虫作用高于MA(SS:52.2μg/ml;RS:170μg/ml)或单独的MTX(SS:22.2μg/ml,RS:51.4μg/ml)。与阳性对照相比,MTX加MA使平均感染率(MIR)和每个巨噬细胞内无鞭毛体的平均数量显著降低(P<0.05)。前鞭毛体与MTX预孵育后,其感染力显著降低(P<0.05)。

结论

本研究表明MTX对MA在抑制敏感和耐葡甲胺锑酸盐菌株前鞭毛体和无鞭毛体阶段生长速率方面具有高效能和协同作用。需要进一步开展研究以在临床环境中评估MTX对利什曼原虫的抗利什曼作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b81/5623913/f222fa69da02/IJPA-12-339-g001.jpg

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