为什么药物性耳毒性在2019年仍然无法预防或治疗?氨基糖苷与顺铂耳毒性的文献综述

Cherrabi Kaoutar
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摘要

耳毒性的定义是由于使用药物引起的耳蜗和/或前庭细胞病变。具体机制的差异,巨大的半逻辑变异性,犯罪药物的异质性,目前临床实践中双分子和组织学方面的不可及性,以及病变后演变的多样性:所有这些因素都使得具有系统的诊断方案和系统的管理共识具有挑战性。用毒性较小或无毒的药物替代的可能性依赖于对分子水平作用机制的特殊理解。具有相同有效作用且毒性较小或无毒的药物将为解决这一医源性问题提供有希望的解决方案。目前来看:在大多数情况下,这些药物是必不可少的。耳毒性的特殊方面,在筛查和诊断方案和分类系统方面缺乏共识,使得很难对不同研究人群进行公正的可比性。单纯的临床和听力学方法是综合征性的,它是在病变发生后才进行评估的,由此产生的分类在早期缺乏特异性、敏感性和预后价值。了解内耳药物诱导病变与每种特定耳毒性分子相关的不同细胞形态,将允许:一方面:在不可逆细胞损伤发生之前建立具有高灵敏度和特异性的诊断测试。另一方面,这将为耳部保护和特定治疗的可能性提供新的见解。耳毒性是一个肥沃的科学研究领域,在过去的十年中,探索取得了长足的进展;从实验的角度来看,双分子方法似乎是有希望的:在生理和病理背景下对内耳蛋白质组、转录组和基因组进行彻底的探索,作为细胞病变早期阶段的潜在生物标志物:临床应用不仅可以更具体地了解医源性耳毒性的不同机制,而且还可以为靶向保护和病变后治疗提供新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Why is Drug-Induced Ototoxicity Still Not Preventable nor is it Treatable in 2019? - A Literature Review of Aminoglycoside and Cisplatin Ototoxicity
Oto-toxicity is defined by cochlear and or vestibular cellular lesions due to the use of drugs. The difference in specific mechanisms, the great semi logical variability, the heterogeneity of incriminated drugs, the inaccessibility to bimolecular and histological aspects in the current clinical practice, and the diverse aspects of post-lesional evolution: Are all factors that make it challenging to have systematic diagnostic protocols and systematic consensuses of management. The possibility of replacement with less or non-toxic drugs relies on the peculiar understanding of mechanisms of action in a molecular level. Drugs with the same efficacious action and less or non-toxicity would offer a promising solution for this iatrogenic problem. For now: In most cases, these drugs are indispensable. The idiosyncratic aspect of ototoxicity, the lack of consensus on screening and diagnostic protocols and classification systems, make it difficult to have an unbiased comparability regarding the different populations studied. The pure clinical and audiometric approach is syndromic, it evaluates lesions after their onset, and the classifications that are inspired from them have little specificity, sensibility and prognostic value in early stages. The understanding of the different cellular modalities of inner ear drug-induced lesions related to each specific oto-toxic molecule, would allow: In the one hand: to establish a diagnostic test with high sensibility and specificity before the onset of irreversible cell damage. And in the other hand, would offer new insights into the possibilities of oto-protection, and specific treatment. Oto-toxicity is a fertile field of scientific research which exploration has gained momentum in the last decade; in an experimental point of view, the bimolecular approach seems to be promising: The thorough exploration of inner ear proteome, transcriptome, and genome in physiological and pathological contexts as potential biomarkers of early stages of cell lesions: The clinical application would not only allow a more specific understanding of different mechanisms of iatrogenic oto-toxicity, but also allow new insights into targeted protective and post-lesional therapies.
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