Examination of the emerging role of transporters in the assessment of nephrotoxicity.

IF 3.9 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-11-01 DOI:10.1080/17425255.2022.2151892

Yujia Chen, Shuanghui Lu, Yingqiong Zhang, Binxin Chen, Hui Zhou, Huidi Jiang

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引用次数: 0

Abstract

Introduction: The kidney is vulnerable to various injuries based on its function in the elimination of many xenobiotics, endogenous substances and metabolites. Since transporters are critical for the renal elimination of those substances, it is urgent to understand the emerging role of transporters in nephrotoxicity.

Areas covered: This review summarizes the contribution of major renal transporters to nephrotoxicity induced by some drugs or toxins; addresses the role of transporter-mediated endogenous metabolic disturbances in nephrotoxicity; and discusses the advantages and disadvantages of in vitro models based on transporter expression and function.

Expert opinion: Due to the crucial role of transporters in the renal disposition of xenobiotics and endogenous substances, it is necessary to further elucidate their renal transport mechanisms and pay more attention to the underlying relationship between the transport of endogenous substances and nephrotoxicity. Considering the species differences in the expression and function of transporters, and the low expression of transporters in general cell models, in vitro humanized models, such as humanized 3D organoids, shows significant promise in nephrotoxicity prediction and mechanism study.

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研究转运体在肾毒性评估中的新作用。

导言:肾脏具有清除许多外源性、内源性物质和代谢物的功能，因此容易受到各种损伤。由于转运蛋白对肾脏清除这些物质至关重要，因此迫切需要了解转运蛋白在肾毒性中的新作用。综述了主要肾转运蛋白在某些药物或毒素引起的肾毒性中的作用;解决转运蛋白介导的内源性代谢紊乱在肾毒性中的作用;并讨论了基于转运蛋白表达和功能的体外模型的优缺点。专家意见:由于转运体在外源性和内源性物质的肾脏处置中起着至关重要的作用，因此有必要进一步阐明其肾脏转运机制，并更加关注内源性物质转运与肾毒性之间的潜在关系。考虑到转运蛋白表达和功能的物种差异，以及转运蛋白在一般细胞模型中的低表达，体外人源化模型，如人源化三维类器官，在肾毒性预测和机制研究中具有重要的前景。

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

Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.