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Prevention and elucidation of the ototoxicity of interferon used for the treatment of hepatitis C

Research Project

Project/Area Number 11671687
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionNagasaki University

Principal Investigator

TANAKA Fujinobu  Nagasaki University, School of Medicine, Assistant, 医学部, 助手 (00284688)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Toshimitsu  Nagasaki University, School of Medicine, Professor, 医学部, 教授 (80133958)
隈上 秀高  長崎大学, 医学部, 助手 (10253650)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordsinterferon / mouse / ABR / EP / subcutaneous injection / intravenous injection / intraperitoneal injection / EP / CM / 聴力障害
Research Abstract

Interferon (IFN) is widely used for the treatment of hepatitis type C.Its ototoxicity has been considered to be one of the side effect by some investigators (Kanda, et al 1994). The aim of this investigation is to evaluate the mechanism of ototoxicity of IFN and to establish the prophylaxis by means of animal experiments. The IFN (Recombinant Mu IFN-β) was administrated by intravenous injection, intraperitoneal injection and subcutaneous injection. As the cochlea of mice does not protrude into the middle ear cavity, administration into the perilymphatic space is not possible.
IFN at a dose of 500000IU/kg was administrated intravenously to mice having body weight of 20g in average. The dose was about 50-100 times as for human for one day. The threshold of ABR in response to the stimulus sound of click, 4 kHz tone burst and 8 kHz tone burst were measured before administration, 30 minutes, 120 minutes, 180 minutes and 1 weeks after administration. The thresholds did not show any remarkable change. In the case with intraperitoneal and subcutaneous administration, 1000000 IU/kg was injected to 20g weighted mice for 21 days. The ABR thresholds were compared to that of control group in which control solution were administrated by the same technique. There were no remarkable difference in the threshold of ABR to click, 4 kHz tone burst and 8 kHz tone burst between the IFN group and the control group. The endocochlear DC potential (EP) was measured in the subcutaneous injection group, but there were no significant difference between IFN group and control group. These preliminary data showed no remarkable histological change. The results obtained in the present investigation failed to show that IFN is toxic to the cochlea.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] 田中藤信 他: "The electrophysiological evaluation about ototoxicity of interferon on mice"American journal of otology. (投稿準備中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujinobu Tanaka, et al.: "The electrophysiological evaluation of ototoxicity of interferon in mice"Preparing for contribution to American journal of otology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 田中藤信、塚崎尚紀、他: "半規管切断時の蝸牛機能―特に吸引の影響について―"Otology Japan. 9(4). 499 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田中藤信、塚崎尚紀、他: "バンコマイシンの耳毒性に関する電気生理学的検討"日耳鼻. 102(4). 102 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tamala F,Tsukasaki N,et al.: "Electrocochleographic evaluation of hearing loss in acoustic tumor"Am J Otol. 20(4). 479-483 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirano K,Kobayashi T,et al: "Prognosis of sudden deafness with special reference to riskfactors of microvascular pathology"Auris Nasus Larynx. 26. 111-115 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kumagami H,et al: "Expression pattern of adenylyl cyclase isoforms in the inner ear of the rat by RT-PCR and immunochemical localization of calcineurin in the organ of Corti"Hearing Research. 132. 69-75 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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