In Vitro Cytotoxic, Genotoxic, Embryotoxic and Oxidative Damage Potentials by Empagliflozin

IF 0.5 4区生物学 Q4 BIOLOGY

Biology Bulletin Pub Date : 2024-02-09 DOI:10.1134/s1062359023603919

Kenan Cadirci, Hasan Turkez, Ozlem Ozdemir Tozlu, Omer Erkan Yapca, Muharrem Bayrak, Bugrahan Emsen, Adil Mardinoglu

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Abstract

Empagliflozin (EMPA) is a potent, competitive and selective sodium glucose cotransporter-2 (SGLT-2) inhibitor that ameliorates blood glucose with the insulin-independent manner. EMPA reduces weight and blood pressure of patients with type 2 diabetes mellitus (T2DM) without developing hypoglycemic risk. To the best of our knowledge, its safety profiling has not been evaluated on human blood cell cultures yet. Again, the embryotoxicity potential by EMPA is still unclear. Therefore, in this investigation we aimed to evaluate the in vitro cytotoxic, genotoxic and embryotoxic damage potential as well as antioxidative/oxidative effects by EMPA in cultured human blood and human pluripotent embryonal carcinoma NT2 cells for the first time. Cell cultures (n = 5) were exposed to different concentrations ranging from 3.25 to 100 mg/L of EMPA for 48 and 72 h. Cell viability was measured by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. The alterations in antioxidant/oxidant activity were monitored via measuring the total antioxidant capacity (TAC) and total oxidative stress (TOS) levels. For evaluating the genotoxicity of EMPA chromosomal aberration (CA) assay was performed. The present results revealed that EMPA did not induce cytotoxic or genotoxic damage on healthy human blood cells. Moreover, EMPA exerted non-embryotoxic property and supported antioxidative capacity and decreased the oxidative stress in cultured human blood cells. Our results supported the safe and advantageous use of EMPA for the treatment of T2DM.

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恩格列净的体外细胞毒性、基因毒性、胚胎毒性和氧化损伤潜力

摘要恩格列净（Empagliflozin，EMPA）是一种强效、竞争性和选择性钠葡萄糖共转运体-2（SGLT-2）抑制剂，能以胰岛素依赖方式改善血糖。EMPA 可降低 2 型糖尿病（T2DM）患者的体重和血压，同时不会产生低血糖风险。据我们所知，尚未在人类血细胞培养物上对其安全性进行评估。此外，EMPA 的胚胎毒性潜力仍不清楚。因此，在这项研究中，我们首次评估了 EMPA 在培养的人类血液和人类多能胚胎癌 NT2 细胞中的体外细胞毒性、基因毒性和胚胎毒性损伤潜力以及抗氧化/氧化作用。细胞培养物（n = 5）暴露于不同浓度（3.25 至 100 毫克/升）的 EMPA 48 和 72 小时后，用 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MTT）和乳酸脱氢酶（LDH）释放试验测定细胞活力。通过测量总抗氧化能力（TAC）和总氧化应激（TOS）水平来监测抗氧化剂/氧化剂活性的变化。为了评估 EMPA 的遗传毒性，进行了染色体畸变（CA）检测。研究结果表明，EMPA 不会对健康人的血细胞造成细胞毒性或遗传毒性损伤。此外，EMPA 还具有无胚胎毒性的特性，并支持抗氧化能力和降低培养人血细胞的氧化应激。我们的研究结果支持将 EMPA 安全、有效地用于治疗 T2DM。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology Bulletin 生物-生物学

CiteScore

0.70

自引率

20.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Biology Bulletin (Izvestiya Rossiiskoi Akademii Nauk – Seriya Biologicheskaya) is an interdisciplinary journal of general biology. It focuses on fundamental studies in the fields of cell biology, biochemistry, zoology, botany, physiology, and ecology. This journal publishes current materials of experimental studies and surveys on current problems in general biology. It also publishes information on scientific conferences and new books in the fields of general biology.