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通过彗星试验和胞质分裂阻滞微核试验评估一种偏头痛特异性药物的遗传毒性潜力。

Assessment of the genotoxic potential of a migraine-specific drug by comet and cytokinesis-block micronucleus assays.

作者信息

Cayir Akin, Cobanoglu Hayal, Coskun Munevver

机构信息

Health Services Vocational College, Çanakkale Onsekiz Mart University, Canakkale, Turkey.

出版信息

Expert Opin Drug Metab Toxicol. 2020 May;16(5):441-446. doi: 10.1080/17425255.2020.1748598. Epub 2020 Apr 10.

Abstract

: Eletriptan is a migraine-specific drug-containing the triptan group. In terms of drug safety, the present study aimed to investigate the genotoxic potential of eletriptan.: We conducted our study by using the cytokinesis-block micronucleus cytome (CBMN) assay, a comprehensive method for measuring micronucleus formation, and a sensitive method for detecting DNA-strand breaks. In the assay, cytokinesis-block proliferation index and the frequency of micronuclei were evaluated in lymphocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for 48 hours. In comet assays, DNA damage was evaluated in leucocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for an hour.: Eletriptan did not induce cytotoxicity nor any increased micronuclei frequencies. While the comet parameters % DNA in tail, tail moment, and the olive moment was found to be significantly increased at 10 and 25 µg/ml, the cytokinesis-block proliferation index values were not.: These findings suggest that eletriptan is non-cytotoxic but potentially weakly genotoxic at higher concentrations (10 and 25 µg/ml).

摘要

依立曲坦是一种含曲坦类的偏头痛特异性药物。在药物安全性方面,本研究旨在调查依立曲坦的遗传毒性潜力。

我们通过使用胞质分裂阻滞微核细胞组(CBMN)试验进行研究,这是一种测量微核形成的综合方法,也是一种检测DNA链断裂的灵敏方法。在该试验中,对用三种不同浓度(1、10和25μg/ml)的依立曲坦处理48小时的淋巴细胞评估胞质分裂阻滞增殖指数和微核频率。在彗星试验中,对用三种不同浓度(1、10和25μg/ml)的依立曲坦处理一小时的白细胞评估DNA损伤。

依立曲坦未诱导细胞毒性,也未使微核频率增加。虽然在10和25μg/ml时发现彗星试验参数尾中DNA%、尾矩和橄榄尾矩显著增加,但胞质分裂阻滞增殖指数值未增加。

这些发现表明,依立曲坦无细胞毒性,但在较高浓度(10和25μg/ml)时可能具有弱遗传毒性。

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