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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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2017-04-01
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| Series: | Biomaterials Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40824-017-0090-x |
| _version_ | 1827334866457329664 |
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| author | Jin Ho Lee Se Heang Oh Tae Ho Kim Yoon Young Go Jae-Jun Song |
| author_facet | Jin Ho Lee Se Heang Oh Tae Ho Kim Yoon Young Go Jae-Jun Song |
| author_sort | Jin Ho Lee |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-07T18:05:00Z |
| format | Article |
| id | doaj.art-e12a2b2edaab466cb6feeb0312e11fac |
| institution | Directory Open Access Journal |
| issn | 2055-7124 |
| language | English |
| last_indexed | 2024-03-07T18:05:00Z |
| publishDate | 2017-04-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Biomaterials Research |
| spelling | doaj.art-e12a2b2edaab466cb6feeb0312e11fac2024-03-02T09:43:48ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials 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 |
| 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 |
| title | 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_short | Anti-apoptotic effect of dexamethasone in an ototoxicity model |
| title_sort | anti apoptotic effect of dexamethasone in an ototoxicity model |
| topic | Explant culture Gentamicin Ototoxicity Dexamethasone |
| url | http://link.springer.com/article/10.1186/s40824-017-0090-x |
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