Cisplatin-Induced Ototoxicity: Effects, Mechanisms and Protection Strategies.
Cisplatin-Induced Ototoxicity: Effects, Mechanisms and Protection Strategies.
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DOI：
10.3390/toxics3030268
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发表时间：
2015-07-15
期刊：
影响因子：
4.6
通讯作者：
Llorens J
中科院分区：
文献类型：
--
作者：
Callejo A;Sedó-Cabezón L;Juan ID;Llorens J
顺铂是一种高效的化疗药物，广泛用于治疗实体器官恶性肿瘤。然而，严重的副作用与其使用有关，例如双侧，进行性，不可逆，剂量依赖性感觉神经性听力损失。目前的证据表明，顺铂触发内耳靶组织中活性氧的产生。各种药物，防止顺铂诱导的耳毒性已成功地在细胞培养和动物模型中进行了测试。然而，它们中的许多干扰顺铂的治疗效果，因此不适合在临床实践中全身给药。因此，局部给药策略，即鼓室内给药，已被开发以实现耳保护，而不降低顺铂的抗肿瘤作用。虽然有相当数量的临床前信息，但预防顺铂耳毒性的治疗方法的临床数据才刚刚开始出现。本文就顺铂耳毒性的临床和实验研究进行综述，重点介绍其毒性机制、临床影响和防治策略。
Cisplatin is a highly effective chemotherapeutic agent that is widely used to treat solid organ malignancies. However, serious side effects have been associated with its use, such as bilateral, progressive, irreversible, dose-dependent neurosensory hearing loss. Current evidence indicates that cisplatin triggers the production of reactive oxygen species in target tissues in the inner ear. A variety of agents that protect against cisplatin-induced ototoxicity have been successfully tested in cell culture and animal models. However, many of them interfere with the therapeutic effect of cisplatin, and therefore are not suitable for systemic administration in clinical practice. Consequently, local administration strategies, namely intratympanic administration, have been developed to achieve otoprotection, without reducing the antitumoral effect of cisplatin. While a considerable amount of pre-clinical information is available, clinical data on treatments to prevent cisplatin ototoxicity are only just beginning to appear. This review summarizes clinical and experimental studies of cisplatin ototoxicity, and focuses on understanding its toxicity mechanisms, clinical repercussions and prevention strategies.