Wei Tong, Nie Jing, Wang Dongbo, Wu Huina, Guan Lijiao, Wu Jiyong
College of Pharmacy, Shandong University of Traditional Chinese Medicine Jinan 250355 P. R. China.
Department of pharmacy, Shandong Second Provincial General Hospital Jinan 250022 P. R. China
RSC Med Chem. 2025 Sep 9. doi: 10.1039/d5md00426h.
Cisplatin remains a cornerstone in the treatment of various solid tumors due to its exceptional antineoplastic efficacy. However, its clinical utility is significantly constrained by severe adverse effects, with ototoxicity emerging as particularly problematic due to its potential to cause permanent hearing impairment and substantially diminish patient quality of life. Recent investigations into mitigating cisplatin-induced ototoxicity have identified natural polyphenolic compounds as promising protective agents, attributable to their diverse biological activities and potent antioxidant properties. This review critically examines the molecular mechanisms underlying cisplatin-induced cochlear damage and systematically evaluates recent advances in employing polyphenolic compounds as otoprotective interventions. Evidence indicates these bioactive molecules attenuate cisplatin-mediated hearing loss through multiple complementary pathways, including modulation of oxidative stress, inflammatory responses, and apoptotic cascades within the cochlear architecture. However, significant challenges, such as low bioavailability and potential interference with cisplatin's antitumor efficacy, hinder their clinical translation. Based on evidence from studies published between 2010 and 2025, with a focus on advances from the last five years, this review systematically outlines protective mechanisms while critically addressing current research limitations. It further proposes future directions, highlighting advanced drug delivery systems and innovative therapeutic strategies. These insights provide a robust mechanistic framework for the rational design and development of novel otoprotective strategies that preserve cisplatin's antitumor efficacy while minimizing its ototoxic potential.
顺铂因其卓越的抗肿瘤疗效，仍然是治疗各种实体瘤的基石。然而，其临床应用受到严重不良反应的显著限制，其中耳毒性尤其成问题，因为它有可能导致永久性听力损伤并大幅降低患者生活质量。最近对减轻顺铂诱导的耳毒性的研究已确定天然多酚类化合物是有前景的保护剂，这归因于它们多样的生物活性和强大的抗氧化特性。本综述批判性地研究了顺铂诱导耳蜗损伤的分子机制，并系统评估了使用多酚类化合物作为耳保护干预措施的最新进展。有证据表明，这些生物活性分子通过多种互补途径减轻顺铂介导的听力损失，包括调节耳蜗结构内的氧化应激、炎症反应和凋亡级联反应。然而，诸如低生物利用度和对顺铂抗肿瘤疗效的潜在干扰等重大挑战阻碍了它们的临床转化。基于2010年至2025年间发表的研究证据，重点关注过去五年的进展，本综述系统地概述了保护机制，同时批判性地解决当前的研究局限性。它还提出了未来的方向，强调了先进的药物递送系统和创新的治疗策略。这些见解为合理设计和开发新的耳保护策略提供了一个强大的机制框架，既能保留顺铂的抗肿瘤疗效，又能将其耳毒性潜力降至最低。
