title: Effects of trolox, locally applied on round windows, on cisplatin-induced ototoxicity in guinea pigs.
abstract: OBJECTIVE
  Cisplatin (CDDP), an antitumor agent widely used in the treatment of pediatric solid tumors, has dose-limiting side effects such as ototoxicity and nephrotoxicity. Recently, evidence has been accumulated to demonstrate that these side effects are closely related to oxidative stress. In the present study, we attempted to suppress CDDP-induced ototoxicity in guinea pigs by administering trolox, a water-soluble analogue of alpha-tocopherol which is a natural lipid-soluble antioxidant, locally on round windows.
  
  
  METHODS
  Hartley albino guinea pigs (250-300 g) were treated with CDDP (0.3 mg/ml) in the presence or absence of a combined treatment of trolox (5 mM). Both drugs were administered locally on round windows.
  
  
  RESULTS
  The combined treatment of trolox distinctly improved the ototoxic side effects induced by CDDP. These were: elevation of auditory brain stem response threshold at 4, 8 and 16 kHz and substantial losses of outer hair cells with the base-to-apex gradient.
  
  
  CONCLUSIONS
  Trolox, locally applied on round windows, showed a suppression on CDDP-ototoxicity. The results obtained in the present study suggest that a local application of trolox in the tympanic cavity can be a promising candidate to prevent the CDDP-ototoxicity in the future.
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. masaaki@med.nagoya-u.ac.jp
authors.forename: Masa-aki
authors.initials: MA
authors.lastname: Teranishi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakashima
mesh_terms: D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001309:Auditory Threshold; D002839:Chromans / Q000494:pharmacology*; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004432:Ear, Middle / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000188:drug therapy*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D018570:Risk Assessment; D012405:Round Window, Ear / Q000187:drug effects; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D002839:Chromans; D002945:Cisplatin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid