Anti-apoptotic effect of dexamethasone in an ototoxicity model

Abstract Background Dexamethasone (DEX) is used for the treatment of various inner ear diseases. However, the molecular mechanism of DEX on gentamicin induced hair cell damage is not known. Therefore, this study investigated the protective effect of DEX on gentamicin (GM)-induced ototoxicity and the...

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Main Authors: Jin Ho Lee, Se Heang Oh, Tae Ho Kim, Yoon Young Go, Jae-Jun Song
Format: Article
Language:English
Published: BioMed Central 2017-04-01
Series:Biomaterials Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40824-017-0090-x
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spelling doaj-art-e12a2b2edaab466cb6feeb0312e11fac2018-08-15T23:22:57ZengBioMed CentralBiomaterials Research2055-71242017-04-012111610.1186/s40824-017-0090-xAnti-apoptotic effect of dexamethasone in an ototoxicity modelJin Ho Lee0Se Heang Oh1Tae Ho Kim2Yoon Young Go3Jae-Jun Song4Department of Advanced Materials, Hannam UniversityDepartment of Nanobiomedical Science & WCU Research Center, Dankook UniversityDepartment of Advanced Materials, Hannam UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Korea University College of MedicineDepartment of Otorhinolaryngology-Head and Neck Surgery, Korea University College of MedicineAbstract Background Dexamethasone (DEX) is used for the treatment of various inner ear diseases. However, the molecular mechanism of DEX on gentamicin induced hair cell damage is not known. Therefore, this study investigated the protective effect of DEX on gentamicin (GM)-induced ototoxicity and the effect of GM on the expression of apoptosis related genes. Methods The protective effects of DEX were measured by phalloidin staining of explant cultures of organ of Corti from postnatal day 2–3 mice with GM-induced hair cell loss. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to detect apoptosis and immunofluorescence was done to analyze the effect of DEX on the expression of apoptosis related genes. Results Cochlear explant cultures of postnatal day-4-old mice were exposed to 0, 1, 5, 10, 30, 50, and 100 μg/ml DEX and GM during culture. DEX protected from GM-induced hair cell loss in the inner ear of postnatal day 4 mice. To understand the molecular mechanisms by which DEX pre-treatment decreased hair cell loss, the testes of cochlear explant cultures of postnatal day 4 mice were examined for changes in expression of cochlear apoptosis mediators. The pro-apoptotic protein Bax was significantly down-regulated and numbers of apoptotic hair cells were decreased. Conclusions DEX has a protective effect on GM-induced hair cell loss in neonatal cochlea cultures and the protective mechanism may involve inhibition of the mitochondrial apoptosis pathway. The combination with scaffold technique can improve delivery of DEX into the inner ear to protect GM-induced ototoxicity.http://link.springer.com/article/10.1186/s40824-017-0090-xExplant cultureGentamicinOtotoxicityDexamethasone
institution Open Data Bank
collection Open Access Journals
building Directory of Open Access Journals
language English
format Article
author Jin Ho Lee
Se Heang Oh
Tae Ho Kim
Yoon Young Go
Jae-Jun Song
spellingShingle Jin Ho Lee
Se Heang Oh
Tae Ho Kim
Yoon Young Go
Jae-Jun Song
Anti-apoptotic effect of dexamethasone in an ototoxicity model
Biomaterials Research
Explant culture
Gentamicin
Ototoxicity
Dexamethasone
author_facet Jin Ho Lee
Se Heang Oh
Tae Ho Kim
Yoon Young Go
Jae-Jun Song
author_sort Jin Ho Lee
title Anti-apoptotic effect of dexamethasone in an ototoxicity model
title_short Anti-apoptotic effect of dexamethasone in an ototoxicity model
title_full Anti-apoptotic effect of dexamethasone in an ototoxicity model
title_fullStr Anti-apoptotic effect of dexamethasone in an ototoxicity model
title_full_unstemmed Anti-apoptotic effect of dexamethasone in an ototoxicity model
title_sort anti-apoptotic effect of dexamethasone in an ototoxicity model
publisher BioMed Central
series Biomaterials Research
issn 2055-7124
publishDate 2017-04-01
description Abstract Background Dexamethasone (DEX) is used for the treatment of various inner ear diseases. However, the molecular mechanism of DEX on gentamicin induced hair cell damage is not known. Therefore, this study investigated the protective effect of DEX on gentamicin (GM)-induced ototoxicity and the effect of GM on the expression of apoptosis related genes. Methods The protective effects of DEX were measured by phalloidin staining of explant cultures of organ of Corti from postnatal day 2–3 mice with GM-induced hair cell loss. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to detect apoptosis and immunofluorescence was done to analyze the effect of DEX on the expression of apoptosis related genes. Results Cochlear explant cultures of postnatal day-4-old mice were exposed to 0, 1, 5, 10, 30, 50, and 100 μg/ml DEX and GM during culture. DEX protected from GM-induced hair cell loss in the inner ear of postnatal day 4 mice. To understand the molecular mechanisms by which DEX pre-treatment decreased hair cell loss, the testes of cochlear explant cultures of postnatal day 4 mice were examined for changes in expression of cochlear apoptosis mediators. The pro-apoptotic protein Bax was significantly down-regulated and numbers of apoptotic hair cells were decreased. Conclusions DEX has a protective effect on GM-induced hair cell loss in neonatal cochlea cultures and the protective mechanism may involve inhibition of the mitochondrial apoptosis pathway. The combination with scaffold technique can improve delivery of DEX into the inner ear to protect GM-induced ototoxicity.
topic Explant culture
Gentamicin
Ototoxicity
Dexamethasone
url http://link.springer.com/article/10.1186/s40824-017-0090-x
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