Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Institute of Otorhinolaryngology, Jinan, Shandong, China.
Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Food Chem Toxicol. 2024 Dec;194:115099. doi: 10.1016/j.fct.2024.115099. Epub 2024 Nov 7.
Cisplatin, a widely used chemotherapy drug, is notorious for causing ototoxicity, which leads to irreversible sensorineural hearing loss by damaging cochlear sensory hair cells (HCs), spiral ganglion neurons (SGNs), and the stria vascularis (SV). Mechanisms include DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammation, ultimately triggering cell death pathways like apoptosis, necroptosis, pyroptosis, or ferroptosis. Apigenin, a natural flavonoid found in various foods and beverages, possesses antioxidant, anti-inflammatory, and anti-tumor properties. Despite these benefits, its potential to mitigate cisplatin-induced ototoxicity remains unexplored. To investigate, we administered varying concentrations of apigenin (1 μM, 20 μM, 100 μM, and 250 μM) alongside cisplatin (200 μM) to zebrafish larvae at 5 days post fertilization. Cisplatin significantly reduced lateral line HCs, impacting auditory function as shown in startle response tests. However, co-administration with apigenin preserved lateral line HCs and mitigated cisplatin-induced hearing loss. In larvae exposed to cisplatin, TUNEL assay confirmed significant HCs apoptosis, which apigenin effectively countered by suppressing reactive oxygen species accumulation in lateral line HCs. RNA-seq analysis highlighted apigenin's role in modulating apoptosis-related pathways, supporting its protective effects against cisplatin-induced ototoxicity. These findings underscore apigenin's potential as a crucial protective agent against cisplatin-induced ototoxicity, meriting further investigation for clinical applications.
顺铂是一种广泛应用的化疗药物，其耳毒性恶名昭著，通过损伤耳蜗感觉毛细胞（HCs）、螺旋神经节神经元（SGNs）和血管纹（SV）导致不可逆的感音神经性听力损失。其机制包括 DNA 加合物形成、线粒体功能障碍、氧化应激和炎症，最终引发细胞死亡途径，如细胞凋亡、坏死性凋亡、细胞焦亡或铁死亡。芹菜素是一种存在于各种食物和饮料中的天然类黄酮，具有抗氧化、抗炎和抗肿瘤特性。尽管有这些益处，但它减轻顺铂诱导的耳毒性的潜力尚未得到探索。为了研究这一点，我们在受精后 5 天向斑马鱼幼虫中添加不同浓度的芹菜素（1 μM、20 μM、100 μM 和 250 μM）和顺铂（200 μM）。顺铂显著减少了侧线 HCs，如惊跳反应测试所示，这影响了听觉功能。然而，与芹菜素共同给药可保护侧线 HCs 并减轻顺铂诱导的听力损失。在暴露于顺铂的幼虫中，TUNEL 测定证实了 HCs 凋亡的显著增加，而芹菜素通过抑制侧线 HCs 中活性氧物质的积累有效地对抗了这种增加。RNA-seq 分析强调了芹菜素在调节凋亡相关途径中的作用，支持了它对顺铂诱导的耳毒性的保护作用。这些发现强调了芹菜素作为一种对抗顺铂诱导的耳毒性的关键保护剂的潜力，值得进一步研究以用于临床应用。
