Chen Zhifeng, Xie Ting, Chen Chenyu, Lin Tingting, Wu Xiaobo, Chen Yuqing, Lin Yanchun, Luo Xiaoyang, Zeng Chaojun, Lin Chang
Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Department of Otorhinolaryngology-Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Front Pharmacol. 2025 Aug 14;16:1641174. doi: 10.3389/fphar.2025.1641174. eCollection 2025.
Cisplatin is a widely used chemotherapy drug for the treatment of solid tumours, but its clinical benefit is often limited by ototoxicity, leading to irreversible sensorineural hearing loss. However, there is a lack of effective strategies to prevent hearing loss caused by cisplatin in adults, while sodium thiosulfate is approved by the Food and Drug Administration in the United States for only use at the pediatric level. Sarsasapogenin, a natural compound of the , has antioxidant and neuroprotective properties, which suggest that it may attenuate the ototoxicity induced by cisplatin. The aim of this study is to evaluate the otoprotective effects of sarsasapogenin and its underlying mechanism as a potential therapeutic intervention for the prevention of ototoxicity induced by cisplatin.
Cell viability was assessed by CCK-8 and cell apoptosis was assessed by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial dysfunction were quantified by immunofluorescence. In addition, expression of the molecules involved in apoptosis and ferroptosis was analyzed by qRT-PCR and Western blot. auditory function was evaluated by auditory brainstem response testing, and the survival of hair cells in the cochlea was quantified by immunolabeling with myosin-VIIa.
Sarsasapogenin significantly alleviated cisplatin-induced oxidative stress and restored mitochondrial function in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. Furthermore, sarsasapogenin effectively protected against cisplatin-induced sensorineural hearing loss and hair cell degeneration . Mechanistically, the protective effects of sarsasapogenin were primarily mediated through the inhibition of apoptosis and ferroptosis, both and .
This study provides compelling evidence for the otoprotective effects of sarsasapogenin, suggesting its potential as a therapeutic intervention to prevent cisplatin-induced hearing loss.
顺铂是一种广泛用于治疗实体瘤的化疗药物，但其临床疗效常受耳毒性限制，可导致不可逆的感音神经性听力损失。然而，目前缺乏有效的策略来预防成人顺铂所致的听力损失，而硫代硫酸钠仅在美国被食品药品监督管理局批准用于儿科。菝葜皂苷元是一种天然化合物，具有抗氧化和神经保护特性，提示其可能减轻顺铂诱导的耳毒性。本研究旨在评估菝葜皂苷元的耳保护作用及其潜在机制，作为预防顺铂诱导耳毒性的一种潜在治疗干预措施。
采用CCK-8法评估细胞活力，通过流式细胞术评估细胞凋亡。通过免疫荧光定量活性氧（ROS）水平和线粒体功能障碍。此外，采用qRT-PCR和蛋白质免疫印迹法分析凋亡和铁死亡相关分子的表达。通过听性脑干反应测试评估听觉功能，并用肌球蛋白VIIa免疫标记定量耳蜗毛细胞的存活情况。
菝葜皂苷元显著减轻顺铂诱导的氧化应激，并恢复了耳科研究所-柯蒂氏器1（HEI-OC1）细胞的线粒体功能。此外，菝葜皂苷元有效预防了顺铂诱导的感音神经性听力损失和毛细胞变性。机制上，菝葜皂苷元的保护作用主要通过抑制凋亡和铁死亡介导。
本研究为菝葜皂苷元的耳保护作用提供了有力证据，表明其作为预防顺铂诱导听力损失的治疗干预措施的潜力。
