Can Intratympanic Dexamethasone Protect against Cisplatin Ototoxicity in Mice with Age‐Related Hearing Loss?

Abstract

To determine whether intratympanic (i.t.) dexamethasone ameliorates cisplatin-induced ototoxicity in a mouse model of presbycusis. Controlled experimental study. Translational science experimental laboratory. Auditory brainstem response (ABR) thresholds of 24-month-old CBA/J-NIA mice treated with cisplatin were compared 7 days after daily i.t. injections of dexamethasone (24 mg/mL) or saline. 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-i.t. and post-i.t. treatment ABR thresholds were available in 13 of 16 mice. In i.t. saline-treated ears, cisplatin produced up to 9.5-dB ABR threshold elevations. In i.t. 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). 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 i.t. 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 i.t. dexamethasone was in the low-frequency region of the cochlea.