title: Can intratympanic dexamethasone protect against cisplatin ototoxicity in mice with age-related hearing loss?
abstract: OBJECTIVE
  To determine whether intratympanic (i.t.) dexamethasone ameliorates cisplatin-induced ototoxicity in a mouse model of presbycusis.
  
  
  METHODS
  Controlled experimental study.
  
  
  METHODS
  Translational science experimental laboratory.
  
  
  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.
authors.affiliation: Department of Surgery, Division of Otolaryngology-Head & Neck Surgery, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. parham@neuron.uchc.edu
authors.forename: Kourosh
authors.initials: K
authors.lastname: Parham
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006319:Hearing Loss, Sensorineural / Q000517:prevention & control*; D015552:Injections, Intralesional; D051379:Mice; D008808:Mice, Inbred CBA; D011304:Presbycusis; D014432:Tympanic Membrane / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; D003907:Dexamethasone; D002945:Cisplatin