title: Protective role of NecroX-5 against neomycin-induced hair cell damage in zebrafish.
abstract: NecroX-5, one of the derivatives of NecroX series compounds, is a mitochondrial reactive oxygen species and reactive nitrogen species scavenger that inhibits cell death against various kinds of oxidative stresses. The objective of the present study was to evaluate the effects of NecroX-5 on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Five days post-fertilization, zebrafish larvae were exposed to 125 μM neomycin and one of the following NecroX-5 concentrations for 1 h: 10, 25, 50, and 75 μM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy (n = 10). The terminal deoxynucleotidyl transferase-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. Ultrastructural changes were evaluated using scanning electron microscopy. NecroX-5 decreased neomycin-induced hair cell loss in the neuromasts (NecroX-5 50 μM: 13.4 ± 2.0 cells, 125 μM neomycin only: 8.1 ± 1.2 cells; n = 10, P < 0.05) and decreased the TUNEL reaction. The ultrastructural analysis showed that the structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 50 μM NecroX-5. NecroX-5 decreased apoptosis and mitochondrial damage. In conclusion, NecroX-5 attenuated neomycin-induced hair cell loss in zebrafish.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Goyang, Gyeonggi, Korea.
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Song
authors.forename: Jiwon
authors.initials: J
authors.lastname: Chang
authors.forename: Jungim
authors.initials: J
authors.lastname: Choi
authors.forename: Gi Jung
authors.initials: GJ
authors.lastname: Im
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; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects / Q000648:ultrastructure; D008928:Mitochondria / Q000187:drug effects; D009355:Neomycin / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C574766:NecroX-5; D020011:Protective Agents; D013450:Sulfones; D009355:Neomycin