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抗高血压药物活性成分吲达帕胺对人淋巴细胞遗传毒性作用的评估。

Assessment of the genotoxic effects of antihypertensive drug active ingredient indapamide in human lymphocytes.

作者信息

Avuloglu-Yilmaz Ece, Yuzbasioglu Deniz, Unal Fatma

机构信息

Vocational School of Technical Sciences, Amasya University, Amasya, Turkey.

Department of Biology, Faculty of Science, Genetic Toxicology Laboratory, Gazi University, Ankara, Turkey.

出版信息

Drug Chem Toxicol. 2023 Mar;46(2):297-303. doi: 10.1080/01480545.2022.2026375. Epub 2022 Jan 11.

Abstract

Hypertension is the most common cardiovascular disease and is also known as high blood pressure. The large majority of hypertensive patients need long-term administration of antihypertensive agents. Indapamide is an orally administered diuretic antihypertensive drug. The present work aimed to assess the possible genotoxic effects of indapamide using four different assays: chromosomal aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet. Lymphocytes from three different donors were exposed to 18.75, 37.50, 75.00, and 100.00 μg/ml indapamide. Additionally, a negative, a positive (mitomycin C = MMC, 0.20 μg/ml), and a solvent control (5.4 μl/ml methanol) were also applied. As a result, it was seen that indapamide did not cause a significant change in CAs and MN frequencies compared to the control. It caused significant damage only at the highest concentration in the comet assay. Similarly, while it did not affect the number of SCEs in the 24-h treatment, it increased the SCE frequency at the two highest concentrations in the 48-h. Mitotic index (MI) decreased at almost all concentrations. Considering all these results, this study revealed that indapamide did not have a significant genotoxic effect in these conditions. To the best of our knowledge, this is the first investigation about the genotoxic effect of indapamide in human lymphocytes .

摘要

高血压是最常见的心血管疾病,也被称为高血压。绝大多数高血压患者需要长期服用抗高血压药物。吲达帕胺是一种口服的利尿降压药。本研究旨在通过四种不同的试验评估吲达帕胺可能的遗传毒性作用:染色体畸变(CA)、姐妹染色单体交换(SCE)、微核(MN)和彗星试验。来自三个不同供体的淋巴细胞暴露于18.75、37.50、75.00和100.00μg/ml的吲达帕胺中。此外,还设置了阴性对照、阳性对照(丝裂霉素C = MMC,0.20μg/ml)和溶剂对照(5.4μl/ml甲醇)。结果发现,与对照组相比,吲达帕胺在染色体畸变和微核频率方面未引起显著变化。仅在彗星试验的最高浓度下它才造成显著损伤。同样,在24小时处理中它不影响姐妹染色单体交换的数量,但在48小时处理的两个最高浓度下它增加了姐妹染色单体交换频率。几乎在所有浓度下有丝分裂指数(MI)都降低。综合所有这些结果,本研究表明吲达帕胺在这些条件下没有显著的遗传毒性作用。据我们所知,这是关于吲达帕胺对人淋巴细胞遗传毒性作用的首次研究。

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