西咪替丁减轻顺铂所致耳毒性

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-02-11 DOI:10.1016/j.tiv.2025.106025

Rahul Sinha , Si Ja Liu , Rebekah Lee , Julia Boyd , Kyla Geary , Dianzheng Zhang

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引用次数: 0

摘要

考虑到有机阳离子转运体2 （OCT2）在顺铂摄取到内耳细胞中的作用，以及西咪替丁是fda批准的药物，对OCT2具有良好的抑制活性，我们假设用西咪替丁抑制OCT2介导的顺铂摄取可以消除或减轻顺铂介导的耳毒性。我们的初步数据显示，顺铂可以以剂量依赖性的方式降低House Ear Institute-Organ of Corti 1 （HEI-OC1）细胞的活力，而西咪替丁可以有效抵消这种顺铂诱导的毒性，而不影响顺铂对癌细胞的作用。因此，这些药物的联合应用可以改善顺铂的耳毒性，而对其抗癌作用的影响最小。

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Using cimetidine to mitigate cisplatin-induced ototoxicity

Given the well-established role of organic cation transporter 2 (OCT2) in cisplatin uptake to the inner ear cells, and the fact that cimetidine is an FDA-approved drug with well-established inhibitory activity against OCT2, we hypothesized that inhibiting OCT2-mediated cisplatin uptake with cimetidine could eliminate or alleviate cisplatin-mediated ototoxicity. Our preliminary data showed that cisplatin can reduce the viability of House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in a dose-dependent manner, and cimetidine can effectively counteract this cisplatin-induced toxicity without affecting cisplatin's effect on cancer cells. Therefore, combined application of these drugs could ameliorate cisplatin ototoxicity with minimal impact on their anti-cancer effect.

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.