Effects of trolox, locally applied on round windows, on cisplatin-induced ototoxicity in guinea pigs.
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.
Teranishi
Masa-aki
MA
Department of Otorhinolaryngology, Graduate School of Medicine, Nagoya University, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. masaaki@med.nagoya-u.ac.jp
Nakashima
Tsutomu
T
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
D000975:Antioxidants; D002839:Chromans; D002945:Cisplatin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid