title: Protective effects of caffeic acid phenethyl ester (CAPE) against neomycin-induced hair cell damage in zebrafish.
abstract: OBJECTIVE
  Caffeic acid phenethyl ester (CAPE) is known to reduce the generation of oxygen-derived free radicals, which is a major mechanism of aminoglycoside-induced ototoxicity. The objective of the present study was to evaluate the effects of CAPE on neomycin-induced ototoxicity in zebrafish (Brn3c: EGFP).
  
  
  METHODS
  Five-day post-fertilization zebrafish larvae (n=10) were exposed to 125 μM neomycin and one of the following CAPE concentrations for 1h: 50, 100, 250, 500, or 1000 μM. Ultrastructural changes were evaluated using scanning electron microscopy (SEM). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) assay and 2-[4-(dimethylamino)styryl]-N-ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis and mitochondrial damage.
  
  
  RESULTS
  CAPE decreased neomycin-induced hair cell loss in the neuromasts (500 μM CAPE: 12.7 ± 1.1 cells, 125 μM neomycin only: 6.3 ± 1.1 cells; n = 10, P < 0.05). In the ultrastructural analysis, structures of mitochondria and hair cells were preserved when exposed to 125 μM neomycin and 500 μM CAPE. CAPE decreased apoptosis and mitochondrial damage.
  
  
  CONCLUSIONS
  In the present study, CAPE attenuated neomycin-induced hair cell damage in zebrafish. The results of the current study suggest that neomycin induces apoptosis, and the apoptotic cell death can be prevented by treatment with CAPE in zebrafish.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Moo Kyun
authors.initials: MK
authors.lastname: Park
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Gi Jung
authors.initials: GJ
authors.lastname: Im
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Chae
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Won-gue
authors.initials: WG
authors.lastname: Han
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Gyu Ho
authors.initials: GH
authors.lastname: Hwang
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Jong Yoon
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Jungim
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Hak Hyun
authors.initials: HH
authors.lastname: Jung
authors.affiliation: Laboratory of Neurodevelopmental Genetics, Graduate School of Medicine, Korea University, Ansan-City, South Korea.
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Chung
authors.affiliation: Laboratory of Neurodevelopmental Genetics, Graduate School of Medicine, Korea University, Ansan-City, South Korea.
authors.forename: Hae-Chul
authors.initials: HC
authors.lastname: Park
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea. Electronic address: mednlaw@korea.ac.kr.
authors.forename: June
authors.initials: J
authors.lastname: Choi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology*; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D023421:Models, Animal; D009355:Neomycin / Q000633:toxicity*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D002109:Caffeic Acids; C055494:caffeic acid phenethyl ester; D009355:Neomycin; D010626:Phenylethyl Alcohol
keywords: Caffeic acid phenethyl ester; Neomycin; Ototoxicity; Zebrafish