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盐酸/netropsin 对阴道毛滴虫临床分离株的活力、细胞病变作用和溶血活性的影响。

Efficacy of netropsin dihydrochloride against the viability, cytopathogenicity and hemolytic activity of Trichomonas vaginalis clinical isolates.

机构信息

Parasitology Department, Faculty of Medicine, Ain-Shams University, Abbasia, Cairo, Egypt.

Parasitology Department, Faculty of Medicine, Ain-Shams University, Abbasia, Cairo, Egypt.

出版信息

J Infect Chemother. 2019 Dec;25(12):955-964. doi: 10.1016/j.jiac.2019.05.015. Epub 2019 Jun 10.

Abstract

Trichomonas vaginalis (T. vaginalis) is a common sexually transmitted infection, affecting the urogenital tract. Trichomoniasis is customarily treated with metronidazole (MTZ). MTZ is known to cause undesirable side effects and there is several reports on MTZ resistant T. vaginalis. Thus, the present study aimed to in-vitro evaluate the activity of DNA minor groove binder drug ''Netropsin dihydrochloride'' against metronidazole-sensitive T. vaginalis isolates (G and U isolates) and resistant T. vaginalis isolate (ATCC50138) (R isolate). Netropsin was tested at concentrations ranging from 3.5 to 200 μg/ml. It showed effectiveness against all isolates with MLC of 12.5 μg/ml for G and U isolates and of 25 μg/ml for R isolate. Cytotoxicity assay of isolates exposed to the respective MLC of netropsin for 42 h showed a highly significant reduction in the death percentage of MCDK cell line as compared to the effect elicited by drug free controls. The hemolytic activity was evaluated by hemolytic assay and by monitoring the interaction of T. vaginalis isolates with human erythrocytes by inverted microscopy and scanning electron microscopy. The hemolytic assay showed (0%) hemolysis of RBCs incubated with T. vaginalis isolates treated with the corresponding MLC of netropsin for 24 h. Scanning electron microscopy revealed cytoskeletal deformities of netropsin treated isolates. Taken together, these observations suggest that netropsin is a promising therapy for T. vaginalis infection affecting its viability, virulence, cytopathogenic and hemolytic activity with a mechanism of action that might overcome T. vaginalis resistance to metronidazole.

摘要

阴道毛滴虫(T. vaginalis)是一种常见的性传播感染,影响泌尿生殖道。滴虫病通常用甲硝唑(MTZ)治疗。已知 MTZ 会引起不良副作用,并且有几篇关于 MTZ 耐药 T. vaginalis 的报告。因此,本研究旨在体外评估 DNA 小沟结合药物“盐酸奈替普林”对甲硝唑敏感的 T. vaginalis 分离株(G 和 U 分离株)和耐药 T. vaginalis 分离株(ATCC50138)(R 分离株)的活性。奈替普林的测试浓度范围为 3.5 至 200μg/ml。它对所有分离株都有效,G 和 U 分离株的 MLC 为 12.5μg/ml,R 分离株的 MLC 为 25μg/ml。将分离株暴露于奈替普林各自 MLC 42 小时后的细胞毒性试验显示,与无药物对照相比,MCDK 细胞系的死亡率显著降低。通过溶血试验和通过倒置显微镜和扫描电子显微镜监测阴道毛滴虫分离株与人红细胞的相互作用来评估溶血活性。溶血试验显示,用甲硝唑敏感的阴道毛滴虫分离株处理的 RBCs 孵育 24 小时后,没有 RBC 发生溶血(0%)。扫描电子显微镜显示奈替普林处理的分离株细胞骨架变形。综上所述,这些观察结果表明,奈替普林是一种有前途的治疗阴道毛滴虫感染的方法,它可以影响其活力、毒力、细胞病变和溶血活性,其作用机制可能克服甲硝唑对阴道毛滴虫的耐药性。

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