title: 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 μM cisplatin and 50 μM, 100 μM, 250 μM, 500 μM, 750 μM, and 1000 μM concentrations of edaravone for 4h. 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 μM: 8.7 ± 1.5 cells, cisplatin 1000 μM 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 μM cisplatin and 750 μM edaravone for 4h.
  
  
  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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Ansan-City, South Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Gi Jung
authors.initials: GJ
authors.lastname: Im
authors.forename: Jiwon
authors.initials: J
authors.lastname: Chang
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Chae
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Kwon
authors.forename: Hak Hyun
authors.initials: HH
authors.lastname: Jung
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Chung
authors.forename: Hae Chul
authors.initials: HC
authors.lastname: Park
authors.forename: June
authors.initials: J
authors.lastname: Choi
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D019610:Cytoprotection / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D011897:Random Allocation; D012680:Sensitivity and Specificity; D015027:Zebrafish
chemical_list: D002945:Cisplatin; D000077553:Edaravone; D000983:Antipyrine