Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai 200233, China; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai 200233, China.
Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Biochem Pharmacol. 2023 Mar;209:115440. doi: 10.1016/j.bcp.2023.115440. Epub 2023 Jan 30.
Cisplatin is commonly used to treat cancers and is associated with a significant risk of irreversible sensorineural hearing loss. However, no effective preventive strategies are available for cisplatin-induced HL. Therefore, significant efforts have been made to discover new drugs protecting cochlear hair cells from cisplatin-induced damage. We found that a new phytochemical, aucubin, attenuated cisplatin-induced apoptosis, the production of reactive oxygen species, and mitochondrial dysfunction in House Ear Institute Organ of Corti 1 cells and cochlear hair cells. Moreover, aucubin attenuated cisplatin-induced sensorineural hearing loss and hair cells loss in vivo. Furthermore, RNA sequencing analysis revealed that the otoprotective effects of aucubin were mainly mediated by increased STAT3 phosphorylation via the PI3K/AKT pathway. Inhibition of the STAT3 signaling pathway with the inhibitor S3I-201 or siRNA disrupted the protective effects of aucubin on cisplatin-induced apoptosis. In conclusion, we identified an otoprotective effect of aucubin. Therefore, aucubin could be used to prevent cisplatin-induced ototoxicity.
顺铂常用于治疗癌症，并伴有不可逆的感音神经性听力损失的重大风险。然而，目前尚无有效的预防策略可用于顺铂引起的 HL。因此，人们做出了巨大努力来发现新的药物，以保护耳蜗毛细胞免受顺铂引起的损伤。我们发现，一种新的植物化学物质，桃叶珊瑚苷，可减轻顺铂诱导的 House Ear Institute 皮质器官 1 细胞和耳蜗毛细胞中的细胞凋亡、活性氧的产生和线粒体功能障碍。此外，桃叶珊瑚苷可减轻体内顺铂引起的感音神经性听力损失和毛细胞损失。此外，RNA 测序分析表明，桃叶珊瑚苷的耳保护作用主要通过 PI3K/AKT 通路增加 STAT3 磷酸化来介导。用抑制剂 S3I-201 或 siRNA 抑制 STAT3 信号通路会破坏桃叶珊瑚苷对顺铂诱导的细胞凋亡的保护作用。总之，我们确定了桃叶珊瑚苷的耳保护作用。因此，桃叶珊瑚苷可用于预防顺铂引起的耳毒性。
