title: End points for cisplatin ototoxicity.
abstract: BACKGROUND
  Hearing loss owing to ototoxicity in humans is usually presumed to be irreversible and stable. Most articles in the literature study the effects of ototoxic agents such as cisplatin only over a few days or weeks. This study focused on the recovery of hearing over several months in mice. The same treatment was applied to guinea pigs to determine whether there were significant differences in response between the two species.
  
  
  METHODS
  Thirty-two mice and 37 guinea pigs were randomized to receive either saline or cisplatin (15 mg/kg). After this exposure, we performed auditory brainstem response (ABR) testing on the mice over 8 months and on the guinea pigs for 1 month.
  
  
  RESULTS
  Hearing loss owing to cisplatin shows significant variability between and within species. In mice, hearing loss is maximal at about 17 dB during the third month after cisplatin administration but actually improves to the level attributable to presbyacusis. Guinea pigs, however, experience greater, approximately 25 dB hearing loss within a month of administration of the same dose of cisplatin, tested with the same protocol.
  
  
  CONCLUSIONS
  In general, ototoxicity end points should be assessed more than 1 month after exposure for animals. Our observation that hearing loss is incomplete before 1 month in mice opens the possibility of studies for preventive treatment during that time.
authors: University of Manitoba, and Sylvie Berard: Health Sciences Centre, Winnipeg, MB.
authors: Kaiser
authors: K
authors: Qureshy
authors: Brian
authors: B
authors: Blakley
authors: Saad
authors: S
authors: Alsaleh
authors: Taeed
authors: T
authors: Quddusi
authors: Sylvie
authors: S
authors: Berard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005500:Follow-Up Studies; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects* / Q000502:physiology; D034381:Hearing Loss / Q000139:chemically induced* / Q000503:physiopathology; D051379:Mice; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D020127:Recovery of Function
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin