Protective mechanism of ferulic acid against neomycin-induced ototoxicity in zebrafish.

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.