title: Intratympanic dexamethasone to prevent cisplatin ototoxicity: a guinea pig model.
abstract: OBJECTIVE
  To determine whether intratympanic administration of dexamethasone reduces ototoxicity from systemic cisplatin.
  
  
  METHODS
  Prospective animal study. Setting. Cisplatin chemotherapy induces ototoxicity manifesting as irreversible, sensorineural hearing loss. This is due to damage to the inner ear structures by free radicals. Steroidal anti-inflammatories have been shown to reduce the formation of free radicals and protect hearing in animal models.
  
  
  METHODS
  Pure tone auditory brainstem responses were obtained in 58 female albino guinea pigs before and 3 days after intraperitoneal (IP) cisplatin chemotherapy. Auditory brainstem responses were also taken up to 1 month after a low dose of cisplatin. Part I consisted of a dosing study to determine the optimal ototoxic dose of cisplatin. In part II, auditory brainstem response thresholds were compared after bilateral intratympanic dexamethasone doses to act as controls. For part III, the otoprotection of dexamethasone against cisplatin was tested in separate bilateral and unilateral studies.
  
  
  RESULTS
  IP injection of 12 mg/kg of cisplatin induced significant hearing loss (57.2 ± 4.4 dB, P < .01) with 0% mortality. Ears treated with intratympanic dexamethasone alone showed no significant threshold changes. Ears that received IP cisplatin and intratympanic dexamethasone showed reduced threshold shifts at 8 kHz when the greatest concentration of dexamethasone was administered.
  
  
  CONCLUSIONS
  Modest intratympanic dexamethasone otoprotection of the guinea pig ear was greatest at the highest concentration tested and occurred in a frequency-dependent manner. Intratympanic dexamethasone presents as a safe, simple, and effective treatment modality to minimize cisplatin ototoxicity without interfering with the chemotherapeutic effects of cisplatin.
authors.affiliation: McGill Auditory Sciences Laboratory, McGill University, Montreal, Quebec, Canada.
authors.forename: Denise
authors.initials: D
authors.lastname: Murphy
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Daniel
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control*; D015552:Injections, Intralesional; D011897:Random Allocation; D016896:Treatment Outcome; D014432:Tympanic Membrane / Q000187:drug effects*
chemical_list: D003907:Dexamethasone; D002945:Cisplatin