Cisplatin ototoxicity mechanism and antagonistic intervention strategy: a scope review.
Cisplatin ototoxicity mechanism and antagonistic intervention strategy: a scope review.
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DOI：
10.3389/fncel.2023.1197051
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发表时间：
2023
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
顺铂是治疗恶性肿瘤的一线化疗药物，临床效果显着，且成本低廉。然而顺铂的耳毒性和神经毒性极大地限制了其临床应用。本文综述了顺铂从外周血转运至内耳的可能途径和分子机制、顺铂对内耳细胞的毒性反应以及导致细胞死亡的级联反应。此外，本文重点介绍了顺铂耐药机制和顺铂耳毒性的最新研究进展。讨论了两种有效的保护机制，抗凋亡和线粒体自噬激活，以及它们在内耳中的相互作用。此外，还描述了目前顺铂耳毒性的临床预防措施和新型治疗药物。最后，本文还预测了减轻顺铂引起的耳毒性的可能药物靶点的前景。其中包括使用抗氧化剂、转运蛋白抑制剂、细胞途径抑制剂、组合药物递送方法以及在临床前研究中显示出前景的其他机制。需要进一步的研究来评估这些方法的有效性和安全性。
Cisplatin is a first-line chemotherapeutic agent in the treatment of malignant tumors with remarkable clinical effects and low cost. However, the ototoxicity and neurotoxicity of cisplatin greatly limit its clinical application. This article reviews the possible pathways and molecular mechanisms of cisplatin trafficking from peripheral blood into the inner ear, the toxic response of cisplatin to inner ear cells, as well as the cascade reactions leading to cell death. Moreover, this article highlights the latest research progress in cisplatin resistance mechanism and cisplatin ototoxicity. Two effective protective mechanisms, anti-apoptosis and mitophagy activation, and their interaction in the inner ear are discussed. Additionally, the current clinical preventive measures and novel therapeutic agents for cisplatin ototoxicity are described. Finally, this article also forecasts the prospect of possible drug targets for mitigating cisplatin-induced ototoxicity. These include the use of antioxidants, inhibitors of transporter proteins, inhibitors of cellular pathways, combination drug delivery methods, and other mechanisms that have shown promise in preclinical studies. Further research is needed to evaluate the efficacy and safety of these approaches.
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影响因子：
14.5
作者：
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影响因子：
5.6
作者：
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通讯作者：
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