PUBLICATION
Protective Effects of Fasudil Against Cisplatin-Induced Ototoxicity in Zebrafish: An In Vivo Study
- Authors
- Lim, K.H., Park, S., Han, E., Baek, H.W., Hyun, K., Hong, S., Kim, H.J., Lee, Y., Rah, Y.C., Choi, J.
- ID
- ZDB-PUB-250109-186
- Date
- 2024
- Source
- International Journal of Molecular Sciences 25(24): (Journal)
- Registered Authors
- Keywords
- ROCK inhibitor, cisplatin, fasudil, hair cell, ototoxicity, zebrafish
- MeSH Terms
-
- Hair Cells, Auditory*/drug effects
- Hair Cells, Auditory*/metabolism
- Animals
- Cisplatin*/adverse effects
- Cisplatin*/toxicity
- rho-Associated Kinases/antagonists & inhibitors
- rho-Associated Kinases/metabolism
- Apoptosis*/drug effects
- Membrane Potential, Mitochondrial/drug effects
- Caspase 3/metabolism
- Protein Kinase Inhibitors/pharmacology
- Larva/drug effects
- Antineoplastic Agents/adverse effects
- Antineoplastic Agents/toxicity
- Zebrafish*
- Ototoxicity*/drug therapy
- Ototoxicity*/etiology
- Ototoxicity*/prevention & control
- Reactive Oxygen Species*/metabolism
- Autophagy*/drug effects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine*/analogs & derivatives
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine*/pharmacology
- Oxidative Stress/drug effects
- Protective Agents/pharmacology
- PubMed
- 39769128 Full text @ Int. J. Mol. Sci.
Citation
Lim, K.H., Park, S., Han, E., Baek, H.W., Hyun, K., Hong, S., Kim, H.J., Lee, Y., Rah, Y.C., Choi, J. (2024) Protective Effects of Fasudil Against Cisplatin-Induced Ototoxicity in Zebrafish: An In Vivo Study. International Journal of Molecular Sciences. 25(24):.
Abstract
While cisplatin is an effective anti-tumor treatment, it induces ototoxicity through mechanisms involving DNA damage, oxidative stress, and programmed cell death. Rho-associated coiled-coil-containing protein kinase (ROCK) is essential for numerous cellular processes, including apoptosis regulation. Studies have suggested that ROCK inhibitors could prevent apoptosis and promote regeneration. We aimed to investigate the protective effects of the ROCK inhibitor fasudil against cisplatin-induced ototoxicity in a zebrafish model. The zebrafish larvae were exposed to 1 mM cisplatin alone or 1 mM cisplatin co-administered with varying concentrations of fasudil for 4 h. The surviving hair cell counts, apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), caspase 3 activity, and autophagy activation were assessed. Rheotaxis behavior was also examined. Cisplatin reduced hair cell counts; increased apoptosis, ROS production, and ΔΨm loss; and activated caspase 3 and autophagy. Fasudil (100 and 500 µM) mitigated cisplatin-induced hair cell loss, reduced apoptosis, and inhibited caspase 3 and autophagy activation. Rheotaxis in zebrafish was preserved by the co-administration of fasudil with cisplatin. Cisplatin induces hair cell apoptosis in zebrafish, whereas fasudil is a promising protective agent against cisplatin-induced ototoxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping