Dexamethasone Protects Against Radiation-induced Loss of Auditory Hair Cells In Vitro.
OBJECTIVE
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.
*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.
Christine
C
Dinh
Si
S
Chen
Kyle
K
Padgett
John
J
Dinh
Fred
F
Telischi
Nagy
N
Elsayyad
Perry
P
Johnson
Simon
S
Angeli
Esperanza
E
Bas
Stefania
S
Goncalves
Adrien
A
Eshraghi
Thomas
T
Van De Water
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000528:radiation effects; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000517:prevention & control; D020287:In Situ Nick-End Labeling; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000187:drug effects / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone