Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish

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Abstract

Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin and a 20μm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100μm of apocynin, significantly decreased caspase-3 activity. Treatment of the cells with a 100μm concentration of apocynin and a 20μm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin-induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250μm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalJournal of Applied Toxicology
Volume33
Issue number2
DOIs
Publication statusPublished - 2013 Feb 1

Fingerprint

Zebrafish
Cisplatin
Cells
Cell Line
Reactive Oxygen Species
Cochlea
Cell death
Cell Death
Auditory Hair Cells
acetovanillone
Bisbenzimidazole
Organ of Corti
Alopecia
In Situ Nick-End Labeling
NADP
Superoxides
Caspase 3
Oxidoreductases
Antioxidants
Apoptosis

Keywords

  • Apocynin
  • Cisplatin
  • HEI-OC1 cells
  • Ototoxicity
  • Zebrafish

ASJC Scopus subject areas

  • Toxicology

Cite this

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title = "Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish",
abstract = "Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin and a 20μm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100μm of apocynin, significantly decreased caspase-3 activity. Treatment of the cells with a 100μm concentration of apocynin and a 20μm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin-induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250μm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.",
keywords = "Apocynin, Cisplatin, HEI-OC1 cells, Ototoxicity, Zebrafish",
author = "June Choi and Im, {Gi Jung} and Jiwon Chang and Sungwon Chae and Lee, {Seung Hoon} and Kwon, {Soon Young} and Chung, {Ah Young} and Park, {Hae Chul} and Jung, {Hak Hyun}",
year = "2013",
month = "2",
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language = "English",
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T1 - Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish

AU - Choi, June

AU - Im, Gi Jung

AU - Chang, Jiwon

AU - Chae, Sungwon

AU - Lee, Seung Hoon

AU - Kwon, Soon Young

AU - Chung, Ah Young

AU - Park, Hae Chul

AU - Jung, Hak Hyun

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin and a 20μm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100μm of apocynin, significantly decreased caspase-3 activity. Treatment of the cells with a 100μm concentration of apocynin and a 20μm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin-induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250μm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.

AB - Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin and a 20μm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100μm of apocynin, significantly decreased caspase-3 activity. Treatment of the cells with a 100μm concentration of apocynin and a 20μm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin-induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250μm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.

KW - Apocynin

KW - Cisplatin

KW - HEI-OC1 cells

KW - Ototoxicity

KW - Zebrafish

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U2 - 10.1002/jat.1729

DO - 10.1002/jat.1729

M3 - Article

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JO - Journal of Applied Toxicology

JF - Journal of Applied Toxicology

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