TY - JOUR
T1 - Ecabet sodium alleviates neomycin-induced hair cell damage
AU - Rah, Yoon Chan
AU - Choi, June
AU - Yoo, Myung Hoon
AU - Yum, Gunhwee
AU - Park, Saemi
AU - Oh, Kyoung Ho
AU - Lee, Seung Hoon
AU - Kwon, Soon Young
AU - Cho, Seung Hyun
AU - Kim, Suhyun
AU - Park, Hae Chul
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/12
Y1 - 2015/12
N2 - 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 1 h. The positive control group was established by 125 μM neomycin-only treatment (1 h) 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.
AB - 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 1 h. The positive control group was established by 125 μM neomycin-only treatment (1 h) 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.
KW - Ecabet sodium
KW - Hair cell
KW - Neomycin
KW - Reactive oxygen species
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=84946719987&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2015.11.007
DO - 10.1016/j.freeradbiomed.2015.11.007
M3 - Article
C2 - 26561773
AN - SCOPUS:84946719987
SN - 0891-5849
VL - 89
SP - 1176
EP - 1183
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -