Ototoxicity among cisplatin, carboplatin, and oxaliplatin in zebrafish model.

Autor: Li KH; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Zhao YY; Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan., Cheng HL; Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan., Yang JJ; Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan., Chien CY; Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Otorhinolaryngology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Otorhinolaryngology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.
Jazyk: angličtina
Zdroj: Environmental toxicology [Environ Toxicol] 2024 Jul; Vol. 39 (7), pp. 4058-4065. Date of Electronic Publication: 2024 Apr 25.
DOI: 10.1002/tox.24285
Abstrakt: 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.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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