Abstract
Objective. To determine whether intratympanic (IT) dexamethasone ameliorates cisplatin-induced ototoxicity in a mouse model of presbycusis.
Study Design. Controlled experimental study.
Setting. Translational science experimental laboratory.
Subjects and Methods. Auditory brainstem response (ABR) thresholds of 24-month-old CBA/J-NIA mice treated with cisplatin were compared 7 days after daily IT injections of dexamethasone (24 mg/mL) or saline.
Results. Because of high (100%) mortality at 16 mg/kg, a single cisplatin dose of 14 mg/kg intraperitoneally was used. At this latter dose, pre-IT and post-IT treatment ABR thresholds were available in 13 of 16 mice. In IT saline–treated ears, cisplatin produced up to 9.5-dB ABR threshold elevations. In IT dexamethasone–treated ears, little protection against cisplatin was observed at 8 or 16 kHz where mean ABR thresholds were elevated. At 24 and 32 kHz, mean ABR threshold elevations were minimal at 0.6 to 1.4 dB. This protection was statistically significant (P ≤ .02).
Conclusions. These results demonstrate, for the first time, a protective effect of a treatment against an ototoxic agent in the presence of age-related hearing loss. In the presence of age-related hearing loss, the protective effect of IT dexamethasone has a frequency gradient, being greatest in the high-frequency region of the cochlea. This latter finding contrasts with our previous report in young mice, in which the protective effect of IT dexamethasone was in the low-frequency region of the cochlea.
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