| Project/Area Number |
05671421
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Otorhinolaryngology
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| Research Institution | FUKUI MEDICAL SCHOOL |
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Principal Investigator |
SAITO Takehisa FUKUI MEDICAL SCHOOL,DEPARTMENT OF OTOLARY NGOLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (10139769)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Tomitaka FUKUI MEDICAL SCHOOL,DEPARTMENT OF OTOLARY BGOLOGY,ASSISTANT, 医学部, 助手 (20214992)
SAKASHITA Tsutomu FUKUI MEDICAL SCHOOL,DEPARTMENT OF OTOLARY BGOLOGY,ASSISTANT, 医学部, 助手 (10205742)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | CISPLATIN / TRANSPLATIN / OTOTOXIC MECHANISM / OUTER HAIR CELLS / CALCIUM CHANNEL / METABOLITE / 電位依存性Ca^<2+>チャンネル / 代謝酵素 / 単離外有毛細胞 |
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| Research Abstract |
It has been proposed by our recent studies that a part of the acute ototoxic mechanism involved the blocking action on the Ca^<2+> channel of outer hair cells and this action might suppress the first step of sound perception system. It has not yet been clarified, however, whether this action lead to chronic ototoxicity or cell death.
In this study, transisomer of cisplatin, transplatin, has been used in vivo and in vitro experiments. As a result, transplatin blocked the Ca^<2+> channel of isolated outer hair cells of the guinea pig to almost the same degree as cisplatin by using conventional patch-clamp technique. However, transplation had no nephrotoxicity and ototoxicity in vivo. From these results, cisplatin may impair the cochlear sensory physiology, but this action may not progress to chronic ototoxicity or cell death.
Concerning the chronic ototoxicity, the toxicity of cisplatin metabolite on isolated outer hair cells was investigated. Isolated outer hair cells of the guinea pig were incubated with hepatic enzymatic fraction (S9) containing cisplatin. The viability of outer hair cells significantly decreased after incubation in this solution. It was suggested that drug metabolites and induction of metabolic enzymes were important facters in chronic ototoxicity.
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