Protective role of trimetazidine against neomycin-induced hair cell damage in Zebrafish

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11 Citations (Scopus)

Abstract

Objectives. Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Methods. Five-day, postfertilization zebrafish larvae were exposed to 125 μM neomycin and one of the following TMZ concentrations for 1 hour: 10 μM, 100 μM, 500 μM, 1,000 μM, 1,500 μM, or 2,000 μM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of hair cells in the control group that were not exposed to neomycin. Ultrastructural changes were evaluated using scanning electron microscopy. Results. TMZ protected against neomycin-induced hair cell loss in the neuromasts (TMZ 1,000 μM, 11.2±0.4 cells; 125 μM neomycin only, 4.2±0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the ultrastructural analysis, structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 1,000 μM TMZ. Conclusion. TMZ attenuated neomycin-induced hair cell loss in zebrafish. The results of this study suggest that neomycin induces apoptosis, and that apoptotic cell death can be prevented by treatment with tremetazidine.

Original languageEnglish
Pages (from-to)219-225
Number of pages7
JournalClinical and Experimental Otorhinolaryngology
Volume6
Issue number4
DOIs
Publication statusPublished - 2013 Dec 1

Fingerprint

Trimetazidine
Neomycin
Zebrafish
Alopecia
DNA Nucleotidylexotransferase
Biotin
Fluorescence Microscopy
Confocal Microscopy
Electron Scanning Microscopy
Free Radicals
Ear
Larva
Cell Survival
Mitochondria
Cell Death
Apoptosis
Oxygen
Control Groups

Keywords

  • Neomycin
  • Ototoxicity
  • Trimetazidine
  • Zebrafish

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Surgery

Cite this

@article{5ca438490fdf452db918f857aff4ff8c,
title = "Protective role of trimetazidine against neomycin-induced hair cell damage in Zebrafish",
abstract = "Objectives. Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Methods. Five-day, postfertilization zebrafish larvae were exposed to 125 μM neomycin and one of the following TMZ concentrations for 1 hour: 10 μM, 100 μM, 500 μM, 1,000 μM, 1,500 μM, or 2,000 μM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of hair cells in the control group that were not exposed to neomycin. Ultrastructural changes were evaluated using scanning electron microscopy. Results. TMZ protected against neomycin-induced hair cell loss in the neuromasts (TMZ 1,000 μM, 11.2±0.4 cells; 125 μM neomycin only, 4.2±0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the ultrastructural analysis, structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 1,000 μM TMZ. Conclusion. TMZ attenuated neomycin-induced hair cell loss in zebrafish. The results of this study suggest that neomycin induces apoptosis, and that apoptotic cell death can be prevented by treatment with tremetazidine.",
keywords = "Neomycin, Ototoxicity, Trimetazidine, Zebrafish",
author = "Jiwon Chang and Im, {Gi Jung} and Sungwon Chae and Lee, {Seung Hoon} and Kwon, {Soon Young} and Jung, {Hak Hyun} and Chung, {Ah Young} and Park, {Hae Chul} and June Choi",
year = "2013",
month = "12",
day = "1",
doi = "10.3342/ceo.2013.6.4.219",
language = "English",
volume = "6",
pages = "219--225",
journal = "Clinical and Experimental Otorhinolaryngology",
issn = "1976-8710",
publisher = "Korean Society of Otolaryngology",
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TY - JOUR

T1 - Protective role of trimetazidine against neomycin-induced hair cell damage in Zebrafish

AU - Chang, Jiwon

AU - Im, Gi Jung

AU - Chae, Sungwon

AU - Lee, Seung Hoon

AU - Kwon, Soon Young

AU - Jung, Hak Hyun

AU - Chung, Ah Young

AU - Park, Hae Chul

AU - Choi, June

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Objectives. Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Methods. Five-day, postfertilization zebrafish larvae were exposed to 125 μM neomycin and one of the following TMZ concentrations for 1 hour: 10 μM, 100 μM, 500 μM, 1,000 μM, 1,500 μM, or 2,000 μM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of hair cells in the control group that were not exposed to neomycin. Ultrastructural changes were evaluated using scanning electron microscopy. Results. TMZ protected against neomycin-induced hair cell loss in the neuromasts (TMZ 1,000 μM, 11.2±0.4 cells; 125 μM neomycin only, 4.2±0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the ultrastructural analysis, structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 1,000 μM TMZ. Conclusion. TMZ attenuated neomycin-induced hair cell loss in zebrafish. The results of this study suggest that neomycin induces apoptosis, and that apoptotic cell death can be prevented by treatment with tremetazidine.

AB - Objectives. Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Methods. Five-day, postfertilization zebrafish larvae were exposed to 125 μM neomycin and one of the following TMZ concentrations for 1 hour: 10 μM, 100 μM, 500 μM, 1,000 μM, 1,500 μM, or 2,000 μM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of hair cells in the control group that were not exposed to neomycin. Ultrastructural changes were evaluated using scanning electron microscopy. Results. TMZ protected against neomycin-induced hair cell loss in the neuromasts (TMZ 1,000 μM, 11.2±0.4 cells; 125 μM neomycin only, 4.2±0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the ultrastructural analysis, structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 1,000 μM TMZ. Conclusion. TMZ attenuated neomycin-induced hair cell loss in zebrafish. The results of this study suggest that neomycin induces apoptosis, and that apoptotic cell death can be prevented by treatment with tremetazidine.

KW - Neomycin

KW - Ototoxicity

KW - Trimetazidine

KW - Zebrafish

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U2 - 10.3342/ceo.2013.6.4.219

DO - 10.3342/ceo.2013.6.4.219

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JO - Clinical and Experimental Otorhinolaryngology

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SN - 1976-8710

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