Platinum‐based antineoplastic drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various cancers. Ototoxicity is a common adverse effect of platinum‐based drugs. Ototoxicity leads to irreversible hearing impairment. We hypothesize that different platinum‐based drugs exhibit varying ototoxic concentrations, time effects, and ototoxic mechanisms. We tested this hypothesis by using a zebrafish model (pvalb3b: TagGFP) to assess the viability of hair cells collected from zebrafish larvae. Cisplatin, carboplatin, and oxaliplatin were administered at dosages of 100, 200, or 400 μM, and the ototoxic effects of these drugs were assessed 1, 2, or 3 h after administration. Fm4‐64 and a TUNEL assay were used to label the membranes of living hair cells and to detect cell apoptosis, respectively. We observed that >50% of hair cells were damaged at 1 h after cisplatin (100 μM) exposure, and this ototoxic effect increased at higher dosages and over time. Owing to the smaller ototoxic effects of carboplatin and oxaliplatin, we conducted higher‐strength and longer‐duration experiments with these drugs. Neither carboplatin nor oxaliplatin was obviously ototoxic, even at 1600 μM and after 6 h. Moreover, only cisplatin damaged the membranes of the hair cells. Cell apoptosis and significantly increased antioxidant gene expression were observed in only the cisplatin group. In conclusion, cisplatin significantly damages sensory hair cells and has notable dosage and time effects. Carboplatin and oxaliplatin are less ototoxic than cisplatin, likely due to having different ototoxic mechanisms than cisplatin.

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顺铂、卡铂和奥沙利铂在斑马鱼模型中的耳毒性

铂类抗肿瘤药物，包括顺铂、卡铂和奥沙利铂，广泛用于治疗各种癌症。耳毒性是铂类药物的常见不良反应。耳毒性会导致不可逆的听力损伤。我们假设不同的铂类药物表现出不同的耳毒性浓度、时间效应和耳毒性机制。我们通过使用斑马鱼模型（pvalb3b：TagGFP）来评估从斑马鱼幼虫中收集的毛细胞的活力来测试这一假设。顺铂、卡铂和奥沙利铂的给药剂量为100、200或400μM，并在给药后1、2或3小时评估这些药物的耳毒性作用。 Fm4-64 和 TUNEL 测定分别用于标记活毛细胞的膜并检测细胞凋亡。我们观察到，暴露于顺铂 (100 μM) 1 小时后，超过 50% 的毛细胞受损，并且这种耳毒性效应随着剂量的增加和时间的推移而增强。由于卡铂和奥沙利铂的耳毒性作用较小，我们对这些药物进行了更高强度和更长持续时间的实验。卡铂和奥沙利铂均没有明显的耳毒性，即使在 1600 μM 浓度和 6 小时后也是如此。此外，只有顺铂会损伤毛细胞的膜。仅在顺铂组中观察到细胞凋亡和抗氧化基因表达显着增加。综上所述，顺铂对感觉毛细胞有显着损伤，且具有显着的剂量和时间效应。卡铂和奥沙利铂的耳毒性低于顺铂，可能是因为其耳毒性机制与顺铂不同。