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维拉帕米对体外培养的热带利什曼原虫前鞭毛体和无鞭毛体阶段对葡甲胺锑的敏感性的影响。

The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate.

机构信息

School of Medicine, Hormozgan University of Medical Sciences, 761-6666367 Bandarabbas, Iran.

出版信息

Parasitol Res. 2012 Mar;110(3):1113-7. doi: 10.1007/s00436-011-2599-6. Epub 2011 Aug 17.


DOI:10.1007/s00436-011-2599-6
PMID:21847598
Abstract

Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis (CL) with low efficacy and resistance is emerging. CL is increased significantly in respect to incidence rate and expanding to new foci. In the present study, the effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate (MA, Glucantime) was evaluated using colorimetric assay (MTT) and in a macrophage model, respectively. Verapamil, as a calcium channel blocker, affects drug uptake by preventing of drug efflux from the cells. In promastigote form, several concentrations of MA with or without verapamil showed significant decrease (P < 0.05) in optical density. The overall mean IC₅₀ value with combination of MA plus verapamil (IC50 = 116.03 μg/ml) was significantly less than MA (IC50 = 225.14 μg/ml) alone (P < 0.05) for promastigote stage. Similarly, the amastigote stage was more susceptible to treatment with MA plus verapamil to that of MA alone (P < 0.05). Analysis of overall effect of different concentrations of MA alone, compared with combination of MA plus verapamil by mean infection rate of amastigotes in each macrophage showed a significant difference (P < 0.05).These findings indicated some degree of synergistic effects between MA and verapamil on in vitro susceptibility of L. tropica to MA. Further works are required to evaluate this synergistic effect on animal model or volunteer human subjects.

摘要

五价锑剂是治疗皮肤利什曼病(CL)的标准药物,但疗效低,且耐药性正在出现。CL 的发病率显著增加,并向新的发病地区扩展。在本研究中,分别使用比色法(MTT)和巨噬细胞模型评估维拉帕米对利什曼原虫(L. tropica)前鞭毛体和无鞭毛体阶段对葡甲胺锑(MA,Glucantime)体外敏感性的影响。维拉帕米作为钙通道阻滞剂,通过阻止药物从细胞中流出,影响药物摄取,从而影响药物的摄取。在前鞭毛体形式中,几种浓度的 MA 与或不与维拉帕米联合使用时,吸光度显著降低(P < 0.05)。与 MA 单独使用相比(IC50 = 225.14 μg/ml),MA 加维拉帕米联合使用的总体平均 IC₅₀ 值(IC50 = 116.03 μg/ml)显著降低(P < 0.05)。同样,无鞭毛体阶段对 MA 加维拉帕米的治疗比单独使用 MA 更敏感(P < 0.05)。通过分析每个巨噬细胞中无鞭毛体的平均感染率,比较 MA 单独使用与 MA 加维拉帕米联合使用对无鞭毛体阶段的总体影响,发现有显著差异(P < 0.05)。这些发现表明 MA 和维拉帕米之间存在一定程度的协同作用,使 L. tropica 对 MA 的体外敏感性增强。需要进一步的工作来评估这种协同作用在动物模型或志愿者人体中的效果。

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本文引用的文献

[1]
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