Melatonin mitigates neomycin-induced hair cell injury in zebrafish

Abstract

Context: Ototoxicity due to medications, such as aminoglycosides, is irreversible, and free radicals in the inner ear are assumed to play a major role. Because melatonin has an antioxidant property, we hypothesize that it might mitigate hair cell injury by aminoglycosides. Objective: The objective of this study was to evaluate whether melatonin has an alleviative effect on neomycin-induced hair cell injury in zebrafish (Danio rerio). Methods: Various concentrations of melatonin were administered to 5-day post-fertilization zebrafish treated with 125 mu M neomycin for 1 h. Surviving hair cells within four neuromasts were compared with that of a control group. Apoptosis was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The changes of ultrastructure were confirmed using a scanning electron microscope. Results: Melatonin alleviated neomycin-induced hair cell injury in neuromasts (neomycin+melatonin 100 mu M: 13.88 +/- 0.91 cells, neomycin only: 7.85 +/- 0.90 cells; n=10, p<0.05) and reduced neomycin-induced apoptosis in the TUNEL assay. In ultrastructural analysis, hair cells within the neuromasts in zebrafish were preserved exposed to 125 mu M neomycin and 100 mu M melatonin for 1 h in SEM findings. Conclusion: Melatonin is effective in alleviating aminoglycoside-induced hair cell injury in zebrafish. The results of this study demonstrated that melatonin has the potential to reduce apoptosis induced by aminoglycosides in zebrafish.