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Protective mechanism of ferulic acid against neomycin-induced ototoxicity in zebrafish
Hsin-Lin Cheng1,2, Shan-Chih Lee2,3, Ju Chang-Chien1
1Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
Abstract:
Ototoxicity refers to damage of sensory hair cells and functional hearing impairment following aminoglycosides exposure. Previously, we have determined that ferulic acid (FA) protected hair cells against serial concentrations of neomycin-induced ototoxic damage. The aim of the present study is to assess the mechanism and effects of FA on neomycin-induced hair cells loss and impact on mechanosensory-mediated behaviors alteration using transgenic zebrafish (pvalb3b: TagGFP). We first identified the optimal protective condition as pre/co-treatment method in early fish development. Pretreatment of the larvae with FA significantly protected against neomycin-induced hair cells loss through preventing neomycin passed through the cytoplasm of hair cells, and subsequently decreased reactive oxygen species production and TUNEL signals in 4 day post-fertilization (dpf) transgenic zebrafish larvae. Moreover, preservation of functional hair cells correlated directly with rescue of the altered swimming behavior, indicates FA pretreatment protects against neomycin ototoxic damage in 7-dpf transgenic zebrafish larvae. Together, our findings unravel the otoprotective role of FA as an effective agent against neomycin-induced ototoxic effects and offering the theoretical foundation for discovering novel candidates for hearing protection.
Insights
Ferulic acid (FA) protects hearing hair cells from neomycin damage by preventing cell entry and reducing oxidative stress. This preserves hearing function and normalizes behavior in zebrafish larvae.
Area of Science:
- Ototoxicity and Hearing Research
- Neuroscience
- Pharmacology
Background:
- Ototoxicity, hearing loss from aminoglycosides, damages sensory hair cells.
- Ferulic acid (FA) previously showed hair cell protection against neomycin.
- The mechanism of FA's otoprotective effects requires further investigation.
Purpose of the Study:
- To elucidate the mechanism of ferulic acid (FA) in protecting against neomycin-induced ototoxicity.
- To evaluate the impact of FA on hair cell loss and behavior in a zebrafish model.
- To identify optimal conditions for FA's protective effects.
Main Methods:
- Utilized transgenic zebrafish (pvalb3b: TagGFP) for visualizing hair cells.
- Determined optimal protective conditions using pre/co-treatment during early development.
- Assessed hair cell loss, reactive oxygen species (ROS) production, and TUNEL signals.
- Monitored mechanosensory-mediated swimming behaviors in larvae.
Main Results:
- FA pretreatment significantly protected hair cells from neomycin-induced loss.
- FA prevented neomycin entry into hair cell cytoplasm, reducing ROS and apoptosis.
- Preservation of hair cells correlated with the rescue of altered swimming behaviors.
- Optimal protection was achieved with pre/co-treatment in early fish development.
Conclusions:
- Ferulic acid (FA) demonstrates significant otoprotective effects against neomycin-induced ototoxicity.
- FA acts by preventing neomycin uptake, reducing oxidative stress, and preserving hair cell function.
- FA pretreatment rescues neomycin-induced behavioral deficits in zebrafish.
- These findings support FA as a potential therapeutic agent for hearing protection.
