Fleihan Tamara, Nader Marc Elie, Dickman J David
Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
Department of Head and Neck Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Front Surg. 2024 Oct 3;11:1437468. doi: 10.3389/fsurg.2024.1437468. eCollection 2024.
Cisplatin, a commonly used chemotherapy drug, is well-established for its ototoxic effects, primarily attributed to the damage it inflicts on cochlear hair cells. However, its impact on the vestibular system remains inadequately understood. Here, we provide a comprehensive review of existing literature concerning cisplatin-induced vestibulotoxicity. Animal studies have shown that cisplatin induces a vestibular hair cell loss that is dose-dependent, with the severity of damage also varying according to the route of administration. Notably, intratympanic and systemic injections in animal models have manifested significant damage primarily to utricular hair cells, with a lesser degree of damage observed for the other vestibular end organs. The underlying mechanisms of cisplatin induced vestibular hair cell loss include apoptosis, oxidative stress, and inflammatory cytokines. Several protective agents, such as Pifithrin-α, DAPT, Ginkgolide B, and heat shock proteins, have demonstrated efficacy in inhibiting cisplatin-induced vestibular damage in preclinical studies. Human clinical findings indicate that cisplatin treatment can cause vestibular dysfunction, characterized by symptoms ranging from transient dizziness to persistent vertigo. Challenges in diagnosis, including the limited utilization of comprehensive vestibular testing for many patients, contribute to the variability in reported outcomes. Cisplatin-induced vestibulotoxicity is a significant complication of chemotherapy, necessitating further research to understand its mechanisms and to improve diagnosis and management, ultimately aiming to enhance the quality of life for cancer patients undergoing cisplatin therapy.
顺铂是一种常用的化疗药物,其耳毒性已得到充分证实,主要归因于它对耳蜗毛细胞造成的损伤。然而,其对前庭系统的影响仍未得到充分了解。在此,我们对有关顺铂诱导的前庭毒性的现有文献进行了全面综述。动物研究表明,顺铂会导致前庭毛细胞丢失,且呈剂量依赖性,损伤的严重程度也因给药途径而异。值得注意的是,在动物模型中,鼓室内注射和全身注射主要对椭圆囊毛细胞造成了显著损伤,而对其他前庭终器的损伤程度较小。顺铂诱导前庭毛细胞丢失的潜在机制包括细胞凋亡、氧化应激和炎性细胞因子。几种保护剂,如匹非尼酮-α、DAPT、银杏内酯B和热休克蛋白,在临床前研究中已证明对抑制顺铂诱导的前庭损伤有效。人类临床研究结果表明,顺铂治疗可导致前庭功能障碍,其症状从短暂头晕到持续性眩晕不等。诊断方面的挑战,包括许多患者对全面前庭测试的使用有限,导致了报告结果的差异。顺铂诱导的前庭毒性是化疗的一个重要并发症,需要进一步研究以了解其机制并改善诊断和管理,最终目标是提高接受顺铂治疗的癌症患者的生活质量。