顺序及原文结构不变：顺铂作为抗癌药物被广泛使用，但由于其严重的副作用——耳毒性，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作用。我们培养了HEI-OC1细胞和新生儿耳蜗。通过免疫荧光染色在体外观察了裂解的半胱氨酸蛋白酶3，TUNEL和MitoSOX红染色体。检测了CCK8和LDH细胞毒性实验以测量细胞存活率和细胞毒性。我们的研究结果表明，Rh1显著增加了细胞存活率，减少了细胞毒性，缓解了顺铂诱导的细胞凋亡。此外，Rh1预处理减少了细胞内反应性氧化物的过度累积。机制研究表明，Rh1预处理逆转了细胞凋亡蛋白表达的增加，线粒体ROS的积累和MAPK信号通路的激活。这些结果表明，Rh1可以作为抗氧化剂和抗凋亡剂对抗顺铂诱导的听力损失，抑制线粒体ROS的过度积累、MAPK信号通路的激活和细胞凋亡。版权所有©2023 Elsevier B.V.出版。

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.Copyright © 2023. Published by Elsevier B.V.