Exposure to ototoxic drugs is a significant cause of hearing loss that affects about 30 thousand children with potentially serious physical, social and psychological dysfunctions every year. Cisplatin (CP) and aminoglycosides are effective antineoplastic or bactericidal drugs, and their application has a high probability of ototoxicity which results from the death of hair cells (HCs). Here, we describe the therapeutic effect of the flavonoid compound naringin (Nar) against ototoxic effects of cisplatin and aminoglycosides include gentamicin (GM) and neomycin (Neo) in zebrafish HCs. Animals incubated with Nar (100‐400 μmol/L) were protected against the pernicious effects of CP (150‐250 μmol/L), GM (50‐150 μmol/L) and Neo (50‐150 μmol/L). We also provide evidence for the potential mechanism of Nar against ototoxicity, including antioxidation, anti‐apoptosis, promoting proliferation and hair cell regeneration. We found that mRNA levels of the apoptotic‐ and pyroptosis‐related genes are regulated by Nar both in vivo and in vitro. Finally, by proving that Nar does not affect the anti‐tumour efficacy of CP and antibacterial activity of aminoglycosides in vitro, we highlight its value in clinical application. In conclusion, these results unravel a novel therapeutic role for Nar as an otoprotective drug against the adverse effects of CP and aminoglycosides.

中文翻译：

---

柚皮素通过多种途径减轻顺铂和氨基糖苷类诱导的斑马鱼侧线毛细胞损伤

接触耳毒性药物是导致听力损失的一个重要原因，每年约有 3 万儿童患有潜在的严重身体、社会和心理功能障碍。顺铂 (CP) 和氨基糖苷类药物是有效的抗肿瘤或杀菌药物，它们的应用具有很高的耳毒性，这是由毛细胞 (HC) 的死亡引起的。在这里，我们描述了黄酮类化合物柚皮苷 (Nar) 对顺铂和氨基糖苷类的耳毒性作用的治疗作用，包括庆大霉素 (GM) 和新霉素 (Neo) 在斑马鱼 HCs 中。用 Nar (100-400 μmol/L) 孵育的动物可免受 CP (150-250 μmol/L)、GM (50-150 μmol/L) 和 Neo (50-150 μmol/L) 的有害影响。我们还为 Nar 抗耳毒性的潜在机制提供了证据，包括抗氧化，抗细胞凋亡，促进增殖和毛细胞再生。我们发现凋亡和焦亡相关基因的 mRNA 水平在体内和体外均受 Nar 调节。最后，通过证明 Nar 在体外不影响 CP 的抗肿瘤功效和氨基糖苷类的抗菌活性，我们突出了其在临床应用中的价值。总之，这些结果揭示了 Nar 作为耳部保护药物对抗 CP 和氨基糖苷类副作用的新治疗作用。我们强调其在临床应用中的价值。总之，这些结果揭示了 Nar 作为耳部保护药物对抗 CP 和氨基糖苷类副作用的新治疗作用。我们强调其在临床应用中的价值。总之，这些结果揭示了 Nar 作为耳部保护药物对抗 CP 和氨基糖苷类副作用的新治疗作用。