Ecabet sodium alleviates neomycin-induced hair cell damage

Yoon Chan Rah; June Choi; Myung Hoon Yoo; Gunhwee Yum; Saemi Park; Kyoung Ho Oh; Seung Hoon Lee; Soon Young Kwon; Seung Hyun Cho; Suhyun Kim; Hae-Chul Park

doi:10.1016/j.freeradbiomed.2015.11.007

Ecabet sodium alleviates neomycin-induced hair cell damage

Free Radic Biol Med. 2015 Dec:89:1176-83. doi: 10.1016/j.freeradbiomed.2015.11.007. Epub 2015 Nov 10.

Authors

Affiliations

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, Korea University, College of Medicine, Seoul, Republic of Korea.
² 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.
³ Soo ENT Clinic, Siheung, Republic of Korea.
⁴ Laboratory of Neurodevelopmental Genetics, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.

PMID: 26561773
DOI: 10.1016/j.freeradbiomed.2015.11.007

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.

Keywords: Ecabet sodium; Hair cell; Neomycin; Reactive oxygen species; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abietanes / pharmacology*
Animals
Apoptosis / drug effects*
Hair Cells, Auditory / drug effects*
Hair Cells, Auditory / pathology
Mitochondria / drug effects*
Mitochondria / pathology
Models, Animal
Neomycin / toxicity*
Protease Inhibitors / pharmacology
Protective Agents / pharmacology*
Protein Synthesis Inhibitors / toxicity
Reactive Oxygen Species / metabolism
Zebrafish / growth & development

Substances

Abietanes
Protease Inhibitors
Protective Agents
Protein Synthesis Inhibitors
Reactive Oxygen Species
ecabet
Neomycin