title: Therapeutic efficacy of topical application of dexamethasone to the round window niche after acoustic trauma caused by intensive impulse noise in guinea pigs.
abstract: OBJECTIVE
  To assess the therapeutic efficacy of dexamethasone administered topically to the round window niche, following acoustic trauma induced by intensive impulse noise, in guinea pigs.
  
  
  METHODS
  Adult, male, albino guinea pigs with a normal Preyer's reflex were exposed to 80 impulse noises (peak value 167 dB, duration 0.5 ms, interval 2 s). Dexamethasone (40 mg/ml) or saline was then topically applied to the round window niche. Each animal's auditory brainstem response was measured before and one day after exposure, and three weeks after topical treatment. Cochlear morphology was examined to assess hair cell loss and spiral ganglion cell damage. To assess oxidative activity, cochlear malondialdehyde and superoxide dismutase concentrations were determined three weeks post-treatment. Following topical application, the pharmacokinetic characteristics of dexamethasone in cochlear perilymph were analysed using high-performance liquid chromatography.
  
  
  RESULTS
  Animals receiving dexamethasone showed reduced noise-induced outer hair cell loss (three weeks post-treatment), and significant attenuation of noise-induced auditory brainstem response threshold shifts (one day post-exposure and three weeks post-treatment), compared with controls. There was no difference in spiral ganglion morphology. Animals receiving dexamethasone also showed a significantly lower malondialdehyde concentration and a higher superoxide dismutase concentration, post-exposure. Following topical application, the perilymph dexamethasone level peaked at 5330.522 µg/ml (15 minutes post-treatment), and was 299.797 µg/ml 360 minutes later.
  
  
  CONCLUSIONS
  Topical application of dexamethasone to the round window niche has protective effects against intensive impulse noise induced trauma in the guinea pig cochlea. This drug can diffuse into the inner ear through the round window membrane and persist in the perilymph for a relatively long period. The mechanism of protection may involve an anti-oxidant effect.
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose and Throat Hospital of Fudan University, Shanghai, China. chifanglu@yahoo.com.cn
authors.forename: F-L
authors.initials: FL
authors.lastname: Chi
authors.forename: M-Q
authors.initials: MQ
authors.lastname: Yang
authors.forename: Y-D
authors.initials: YD
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Wang
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010498:Perilymph / Q000737:chemistry*; D020127:Recovery of Function / Q000187:drug effects; D012405:Round Window, Ear / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D005938:Glucocorticoids; D008315:Malondialdehyde; D003907:Dexamethasone; D013482:Superoxide Dismutase