Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, China.
ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200031, China.
Biochim Biophys Acta Mol Cell Res. 2023 Jun;1870(5):119461. doi: 10.1016/j.bbamcr.2023.119461. Epub 2023 Mar 15.
As an anticancer drug, cisplatin is widely used, but its clinical application is restricted due to its severe side effects of ototoxicity. Therefore, this study was dedicated to assessing the benefit of ginsenoside extract, 20(S)-Ginsenoside Rh1 (Rh1), on cisplatin-induced ototoxicity. HEI-OC1 cells and neonatal cochlear explants were cultured. Cleaved caspase-3, TUNEL, and MitoSOX Red were observed in vitro by immunofluorescence staining. CCK8 and LDH cytotoxicity assays were detected to measure cell viability and cytotoxicity. Our results showed that Rh1 significantly increased cell viability, reduced cytotoxicity, and alleviated cisplatin-induced apoptosis. In addition, Rh1 pretreatment decreased the excessive accumulation of intracellular reactive oxygen species. Mechanistic studies indicated that Rh1 pretreatment reversed the increase of apoptotic protein expression, accumulation of mitochondrial ROS, and activation of the MAPK signaling pathway. These results suggested that Rh1 can act as an antioxidant and anti-apoptotic agent against cisplatin-induced hearing loss by suppressing the excessive accumulation of mitochondrial ROS, activation of MAPK signaling pathway and apoptosis.
作为一种抗癌药物，顺铂被广泛应用，但由于其严重的耳毒性副作用，其临床应用受到限制。因此，本研究旨在评估人参皂苷提取物 20(S)-人参皂苷 Rh1（Rh1）对顺铂诱导的耳毒性的益处。体外培养 HEI-OC1 细胞和新生耳蜗外植体。通过免疫荧光染色观察体外裂解的 caspase-3、TUNEL 和 MitoSOX Red。通过 CCK8 和 LDH 细胞毒性检测来测量细胞活力和细胞毒性。结果表明，Rh1 显著增加细胞活力，降低细胞毒性，并减轻顺铂诱导的细胞凋亡。此外，Rh1 预处理可减少细胞内活性氧的过度积累。机制研究表明，Rh1 预处理可逆转凋亡蛋白表达增加、线粒体 ROS 积累和 MAPK 信号通路激活。这些结果表明，Rh1 可通过抑制线粒体 ROS 的过度积累、MAPK 信号通路的激活和细胞凋亡，作为一种抗氧化剂和抗凋亡剂来对抗顺铂诱导的听力损失。
