Protective effects of edaravone against cisplatin-induced hair cell damage in zebrafish

Abstract

Objective: Edaravone is known to have a potent free radical scavenging effect. The objective of the present study was to evaluate the effects of edaravone on cisplatin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Methods: Five day post-fertilization zebrafish larvae were exposed to 1000 mu M cisplatin and 50 mu M, 100 mu M, 250 mu M, 500 mu M, 750 mu M, and 1000 mu M concentrations of edaravone for 4 h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy and confocal microscopy (n = 10). Hair cell survival was calculated as a percentage of the hair cells in the control group that were not exposed to cisplatin. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy. Results: Edaravone protected cisplatin-induced hair cell loss of neuromasts (edaravone 750 mu M: 8.7 +/- 1.5 cells, cisplatin 1000 mu M only: 3.7 +/- 0.9 cells; n = 10, p<0.0001) and decreased the Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. Structures of mitochondria and hair cell within neuromasts in ultrastructural analysis were preserved in zebrafish exposed to 1000 mu M cisplatin and 750 mu M edaravone for 4 h. Conclusions: Edaravone attenuated cisplatin-induced hair cell damage in zebrafish. The results of the current study suggest that cisplatin induces apoptosis, and the apoptotic cell death can be prevented by treatment with edaravone in zebrafish. (C) 2013 Elsevier Ireland Ltd. All rights reserved.