Molecular biological investigation for the treatment of inner ear disorders by controlling the free radicals t Medical

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Involvement of free radicals and nitric oxide (NO) in the certain inner ear disorders was investigated in order to found a way to study the mechanisms of inner ear disease. The localization of NO synthase (NOS) isoforms and free radicals were examined in inner ear of the normal and pathological guinea pig by immunohistochemistry. Production of NO in the isolated utricle or in the isolated vestibular hair cells after stimulation with L-arginine, glutamate, and gentamicin was investigated using DAF-2DA. Immunohistochemical stuandy demonstrated the expression for NOS II activity in the pathological inner ear. Production of NO in the inner ear was investigated using the fluorescence indicator, DAF-2DA for direct detection of NO. The fluorescence intensity of the sensory cells was augmented by stimulation with L-arginine, glutamate and gentamicin. The significant increase in NO production in the pathological animals was also noticed. These findings imply that NO from cNOS may mediate ototoxicity in the early phase whereas NO from NOS II may contribute to the late phase of tissue damage in the inner ear. For the aim to develop the new treatment of inner ear disorders, we performed a trial to assess the efficacy of the free-radical scavenger, rebamipide, in the treatment of Meniere' s disease and cisplatin-induced ototoxicity. Over 50% patients showed improvement of vertigo, healing disorders, tinnitus and disability in the Meniere's disease. Over 80% patients showed improvement of hearing in the cisplatin-induced ototoxicity. It has been suggested that treatment by controlling free radicals has a possibility to be an effective new therapy for inner ear disorders.These results were presented at meetings (8th and 9th meetings of Otological Society of Japan 57th and 58th meetings of Japan Society for equilibrium Research, 100th meeting of Oto-Rhino-Laryngological Society of Japan) and were presented by 12 papers .