title: Cisplatin-Induced Ototoxicity and the Effects of Intratympanic Diltiazem in a Mouse Model.
abstract: OBJECTIVE
  To evaluate whether the calcium-channel blocker diltiazem has protective effects against cisplatin-induced ototoxicity in a mouse model.
  
  
  METHODS
  Original basic science in vivo investigation.
  
  
  METHODS
  Academic setting: Otolaryngology-Head and Neck Surgery laboratory at University of Connecticut Health Center.
  
  
  METHODS
  Thirty-nine female CBA/J mice.
  
  
  METHODS
  Pure tone- or click-evoked auditory brainstem responses (ABRs) were recorded in CBA/J mice to determine auditory thresholds. All mice had baseline ABRs recorded. They were then given a single cisplatin bolus (14 mg/kg), followed by 5 consecutive days of intratympanic diltiazem or saline control. Follow-up thresholds were recorded on days 7, 14, and 21 postcisplatin. Tone-evoked ABRs evaluated the otoprotective effect of 2-mg/kg diltiazem in 9 mice, and dose effect was examined in response to click-evoked ABR with 2- or 4-mg/kg diltiazem in 2 groups of 15 mice.
  
  
  RESULTS
  Saline-treated ears had significantly elevated tone-evoked auditory thresholds when compared with diltiazem-treated ears (P = .038) on day 7 postcisplatin only. Click-evoked ABR thresholds were significantly elevated in saline-treated ears versus diltiazem-treated ears for the 2-mg/kg group (P = .001) and 4-mg/kg group (P = .011) on days 7, 14, and 21 postcisplatin.
  
  
  CONCLUSIONS
  Intratympanic diltiazem has significant protective effects against cisplatin ototoxicity at 2 and 4 mg/kg. This is the first in vivo study to demonstrate that diltiazem offers a potentially novel therapy for cisplatin-induced ototoxicity.
authors.affiliation: University of Connecticut Health Center, Farmington, Connecticut, USA Jnaples1@resident.uchc.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Naples
authors.affiliation: University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Parham
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects*; D004110:Diltiazem / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004427:Ear Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D005260:Female; D000069555:Injection, Intratympanic; D051379:Mice; D008808:Mice, Inbred CBA
chemical_list: D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D004110:Diltiazem; D002945:Cisplatin
keywords: calcium; cisplatin; diltiazem; hearing loss; ototoxicity