地塞米松在体外可预防辐射诱导的听觉毛细胞损失。

Dexamethasone Protects Against Radiation-induced Loss of Auditory Hair Cells In Vitro.

作者信息

Dinh Christine, Chen Si, Padgett Kyle, Dinh John, Telischi Fred, Elsayyad Nagy, Johnson Perry, Angeli Simon, Bas Esperanza, Goncalves Stefania, Eshraghi Adrien, Van De Water Thomas

机构信息

*Department of Otolaryngology, University of Miami Miller School of Medicine, University of Miami Ear Institute †Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida, U.S.A.

出版信息

Otol Neurotol. 2015 Dec;36(10):1741-7. doi: 10.1097/MAO.0000000000000850.

DOI:10.1097/MAO.0000000000000850

PMID:26485588

Abstract

HYPOTHESIS

Dexamethasone (DXM) protects against radiation-induced loss of auditory hair cells (HCs) in rat organ of Corti (OC) explants by reducing levels of oxidative stress and apoptosis.

BACKGROUND

Radiation-induced sensorineural hearing loss (HL) is progressive, dose-dependent, and irreversible. Currently, there are no preventative therapeutic modalities for radiation-induced HL. DXM is a synthetic steroid that can potentially target many of the pathways involved in radiation-induced ototoxicity.

METHODS

Whole OC explants were dissected from 3-day-old rat cochleae exposed to specific dosages of single-fraction radiation (0, 2, 5, 10, or 20 Gy), were either untreated or treated with DXM (75, 150, 300 μg/mL), and then cultured for 48 or 96 hours. Confocal microscopy for oxidative stress (CellRox, 48 h) and apoptosis (TUNEL assay, 96 h) and fluorescent microscopy for viable HC counts (fluorescein isothiocyanate-phalloidin, 96 h) were performed. Analysis of variance and Tukey post hoc testing were used for statistical analysis.

RESULTS

Radiation exposure initiated dose-dependent losses of inner and outer HCs, predominantly in the basal turns of the OC explants. DXM protected against radiation-induced HC losses in a dose-dependent manner. DXM significantly reduced levels of oxidative stress and apoptosis in radiation-injured OC explants (p < 0.001).

CONCLUSIONS

Radiation-initiated HC losses were dose-dependent in OC explants. DXM treatment protected explant HCs against radiation-initiated losses by decreasing the levels of oxidative stress and apoptosis. DXM may potentially be a therapeutic modality for preventing radiation-induced HL; further in vivo studies are necessary.

摘要

假设

地塞米松（DXM）通过降低氧化应激和细胞凋亡水平，保护大鼠柯蒂氏器（OC）外植体免受辐射诱导的听觉毛细胞（HCs）损失。

背景

辐射诱导的感音神经性听力损失（HL）是渐进性的、剂量依赖性的且不可逆的。目前，尚无针对辐射诱导HL的预防性治疗方法。DXM是一种合成类固醇，可能靶向参与辐射诱导耳毒性的许多途径。

方法

从暴露于特定剂量单次分割辐射（0、2、5、10或20 Gy）的3日龄大鼠耳蜗中解剖出完整的OC外植体，不进行处理或用DXM（75、150、300 μg/mL）处理，然后培养48或96小时。进行氧化应激（CellRox，48小时）和细胞凋亡（TUNEL检测，96小时）的共聚焦显微镜检查以及存活HC计数（异硫氰酸荧光素 - 鬼笔环肽，96小时）的荧光显微镜检查。采用方差分析和Tukey事后检验进行统计分析。