PUBLICATION

Ecabet sodium alleviates neomycin-induced hair cell damage

Authors
Rah, Y.C., Choi, J., Yoo, M.H., Yum, G., Park, S., Oh, K.H., Lee, S.H., Kwon, S.Y., Cho, S.H., Kim, S., Park, H.C.
ID
ZDB-PUB-151114-13
Date
2015
Source
Free radical biology & medicine   89: 1176-83 (Journal)
Registered Authors
Kim, Suhyun, Park, Hae-Chul
Keywords
Ecabet Sodium, Hair cell, Neomycin, Reactive oxygen species, Zebrafish
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
PubMed
26561773 Full text @ Free Radic. Biol. Med.
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 80μg/mL for 1 h, followed by 125μM neomycin for 1h. The positive control group was established by 125μM neomycin-only treatment (1hr) 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 40μM/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 125μM neomycin treatment than the negative control group and significantly decreased down to 105%with the pre-treatment with 40μM/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 40μM/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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping