title: Ecabet sodium alleviates neomycin-induced hair cell damage.
abstract: Ecabet sodium (ES) is currently applied to some clinical gastrointestinal disease primarily by the inhibition of the ROS production. In this study, the protective role of ES was evaluated against the neomycin-induced hair cell loss using zebrafish experimental animal model. Zebrafish larvae (5-7 dpf), were treated with each of the following concentrations of ES: 5, 10, 20, 40, and 80 μg/mL for 1 h, followed by 125 μM neomycin for 1h. The positive control group was established by 125 μM neomycin-only treatment (1h) and the negative control group with no additional chemicals was also established. Hair cells inside four neuromasts ( SO1, SO2, O1, OC1) were assessed using fluorescence microscopy (n = 10). Hair cell survival was calculated as the mean number of viable hair cells for each group. Apoptosis and mitochondrial damage were investigated using special staining (TUNEL and DASPEI assay, respectively), and compared among groups. Ultrastructural changes were evaluated using scanning electron microscopy. Pre-treatment group with ES increased the mean number of viable hair cells as a dose-dependent manner achieving almost same number of viable hair cells with 40 μM/ml ES treatment (12.98 ± 2.59 cells) comparing to that of the negative control group (14.15 ± 1.39 cells, p = 0.72) and significantly more number of viable hair cells than that of the positive control group (7.45 ± 0.91 cells, p < 0.01). The production of reactive oxygen species significantly increased by 183% with 125 μM neomycin treatment than the negative control group and significantly decreased down to 105% with the pre-treatment with 40 μM/ml ES (n = 40, p = 0.04). A significantly less number of TUNEL-positive cells (reflecting apoptosis, p < 0.01) and a significantly increased DASPEI reactivity (reflecting viable mitochondria, p < 0.01) were observed in 40 μM/ml ES pre-treatment group. Our data suggest that ES could protect against neomycin-induced hair cell loss possibly by reducing apoptosis, mitochondrial damages, and the ROS generation.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon Chan
authors.initials: YC
authors.lastname: Rah
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea. Electronic address: mednlaw@korea.ac.kr.
authors.forename: June
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Myung Hoon
authors.initials: MH
authors.lastname: Yoo
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Gunhwee
authors.initials: G
authors.lastname: Yum
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Saemi
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoung Ho
authors.initials: KH
authors.lastname: Oh
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Kwon
authors.affiliation: Soo ENT Clinic, Siheung, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Laboratory of Neurodevelopmental Genetics, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Suhyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Laboratory of Neurodevelopmental Genetics, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hae-Chul
authors.initials: HC
authors.lastname: Park
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D023421:Models, Animal; D009355:Neomycin / Q000633:toxicity*; D011480:Protease Inhibitors / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development
chemical_list: D045784:Abietanes; D011480:Protease Inhibitors; D020011:Protective Agents; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; C061681:ecabet; D009355:Neomycin
keywords: Ecabet sodium; Hair cell; Neomycin; Reactive oxygen species; Zebrafish