Protective effects of Y-27632 against cisplatin-induced ototoxicity: A zebrafish model Y-27632 and cisplatin-induced ototoxicity.

Kang Hyeon Lim, Saemi Park, Eunjung Han, Hee Soo Yoon, Yunkyoung Lee, Sumin Hong, Kyungtae Hyun, Seung Hwa Baek, Hyun Woo Baek, Yoon Chan Rah, June Choi

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2024 Aug

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Cisplatin is an effective chemotherapy agent against various solid malignancies; however, it is associated with irreversible bilateral sensorineural hearing loss, emphasizing the need for drug development to prevent this complication, with the current options being very limited. Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine-threonine protein kinase involved in various cellular processes, including apoptosis regulation. In this study, we used a transgenic zebrafish model (Brn3C: EGFP) in which hair cells within neuromasts are observed in green under fluorescent microscopy without the need for staining. Zebrafish larvae were exposed to cisplatin alone or in combination with various concentrations of Y-27632, a potent ROCK inhibitor. Hair cell counts, apoptosis assessments using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, FM1-43FX labeling assay and behavioral analyses (startle response and rheotaxis) were performed to evaluate the protective effects of Y-27632 against cisplatin-induced ototoxicity. Cisplatin treatment reduced the number of hair cells in neuromasts, induced apoptosis, and impaired zebrafish larval behaviors. Y-27632 demonstrated a dose-dependent protective effect against cisplatin-induced hair cell loss and apoptosis. These findings suggest that Y-27632, as a ROCK inhibitor, mitigates cisplatin-induced hair cell loss and associated ototoxicity in zebrafish. Copyright © 2024 Elsevier Ltd. All rights reserved.

Citation

Kang Hyeon Lim, Saemi Park, Eunjung Han, Hee Soo Yoon, Yunkyoung Lee, Sumin Hong, Kyungtae Hyun, Seung Hwa Baek, Hyun Woo Baek, Yoon Chan Rah, June Choi. Protective effects of Y-27632 against cisplatin-induced ototoxicity: A zebrafish model Y-27632 and cisplatin-induced ototoxicity. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2024 Aug;190:114792