Can intratympanic dexamethasone protect against cisplatin ototoxicity in mice with age-related hearing loss?

Otolaryngol Head Neck Surg. 2011 Oct;145(4):635-40. doi: 10.1177/0194599811409304. Epub 2011 May 13.

Abstract

Objective: To determine whether intratympanic (i.t.) 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 i.t. 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-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).

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Cisplatin / adverse effects*
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use*
  • Disease Models, Animal
  • Evoked Potentials, Auditory, Brain Stem
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use*
  • Hearing Loss, Sensorineural / prevention & control*
  • Injections, Intralesional
  • Mice
  • Mice, Inbred CBA
  • Presbycusis
  • Tympanic Membrane / drug effects

Substances

  • Antineoplastic Agents
  • Glucocorticoids
  • Dexamethasone
  • Cisplatin