Anti-apoptotic effect of dexamethasone in an ototoxicity model

被引：10
作者：
Lee J.H. [1 ]
Oh S.H. [2 ,3 ]
Kim T.H. [1 ]
Go Y.Y. [2 ,3 ]
Song J.-J. [2 ,3 ]
机构：
[1] Department of Advanced Materials, Hannam University, Daejeon
[2] Department of Nanobiomedical Science and WCU Research Center, Dankook University, Cheonan
[3] Department of Nanobiomedical Science and WCU Research Center, Dankook University, Cheonan
来源：
Biomaterials Research | / 21卷 / 1期
关键词：
Dexamethasone; Explant culture; Gentamicin; Ototoxicity;
D O I：
10.1186/s40824-017-0090-x
中图分类号：
学科分类号：
摘要：
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. © The Author(s). 2017.
引用
收藏
相关论文
共 32 条
[1]  
Park M.K., Lee B.D., Chae S.W., Chi J., Kwon S.K., Song J.J., Protective effect of NecroX, a novel necroptosis inhibitor, on gentamicin-induced ototoxicity, Int J Pediatr Otorhinolaryngol., 76, 9, pp. 1265-1269, (2012)
[2]  
Tange R.A., Dreschler W.A., Prins J.M., Buller H.R., Kuijper E.J., Speelman P., Ototoxicity and nephrotoxicity of gentamicin vs netilmicin in patients with serious infections, A randomized clinical trial. Clin Otolaryngol Allied Sci., 20, 2, pp. 118-123, (1995)
[3]  
Mulheran M., Degg C., Burr S., Morgan D.W., Stableforth D.E., Occurrence and risk of cochleotoxicity in cystic fibrosis patients receiving repeated highdose aminoglycoside therapy, Antimicrob Agents Chemother., 45, 9, pp. 2502-2509, (2001)
[4]  
Sha S.H., Schacht J., Antioxidants attenuate gentamicin-induced free radical formation in vitro and ototoxicity in vivo: D-methionine is a potential protectant, Hear Res., 142, 1-2, pp. 34-40, (2000)
[5]  
Davis R.J., Signal transduction by the JNK group of MAP kinases, Cell., 103, 2, pp. 239-252, (2000)
[6]  
Albinger-Hegyi A., Hegyi I., Nagy I., Bodmer M., Schmid S., Bodmer D., Alteration of activator protein 1 DNA binding activity in gentamicin-induced hair cell degeneration, Neuroscience., 137, 3, pp. 971-980, (2006)
[7]  
Theopold H.M., Comparative surface studies of ototoxic effects of various aminoglycoside antibiotics on the organ of Corti in the guinea pig, A scanning electron microscopic study. Acta Otolaryngol., 84, 1-2, pp. 57-64, (1977)
[8]  
Shafik A.G., Elkabarity R.H., Thabet M.T., Soliman N.B., Kalleny N.K., Effect of intratympanic dexamethasone administration on cisplatin-induced ototoxicity in adult guinea pigs, Auris Nasus Larynx., 40, 1, pp. 51-60, (2013)
[9]  
Topdag M., Iseri M., Gelenli E., Yardimoglu M., Yazir Y., Ulubil S.A., Topdag D.O., Ustundag E., Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, J Laryngol Otol., 126, 11, pp. 1091-1096, (2012)
[10]  
Arvier M., Lagoutte L., Johnson G., Dumas J.F., Sion B., Grizard G., Malthiery Y., Simard G., Ritz P., Adenine nucleotide translocator promotes oxidative phosphorylation and mild uncoupling in mitochondria after dexamethasone treatment, Am J Physiol Endocrinol Metab., 293, 5, pp. E1320-E1324, (2007)
1234