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Abstract：
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.
摘要：
顺铂是治疗恶性肿瘤的一线化疗药物,临床效果显著,费用低廉。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进入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，本文重点介绍顺铂耐药机制及顺铂耳毒性的最新研究进展。两种有效的保护机制，抗凋亡和线粒体自噬激活，并讨论了它们在内耳中的相互作用。此外,介绍了目前临床上对顺铂耳毒性的预防措施和新的治疗药物。最后,本文还预测了减轻顺铂诱导的耳毒性的可能药物靶点的前景。这些包括使用抗氧化剂，转运蛋白的抑制剂，细胞通路的抑制剂，联合给药方法，以及在临床前研究中显示出希望的其他机制。需要进一步的研究来评估这些方法的有效性和安全性。
