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Non-invasive evaluation of free radical reactions accompanied with induction and development of heart failure by in vivo ESR-CT

Research Project

Project/Area Number 12470526
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

UTSUMI Hideo  Graduate school, Faculty of Pharmaceutical Sciences, Kyushu University, Professor, 大学院・薬学研究院, 教授 (20101694)

Co-Investigator(Kenkyū-buntansha) KOSHIISHI Ichiro  Graduate school, Faculty of Pharmaceutical Sciences, Kyushu University, Associate Professor, 大学院・薬学研究院, 助教授 (20170235)
TSUTSUI Hiroyuki  Graduate school, Faculty of Pharmaceutical Sciences, Kyushu University, Lecturer, 大学院・医学系研究院, 講師 (70264017)
SHIMOKAWA Hiroaki  Graduate school, Faculty of Pharmaceutical Sciences, Kyushu University, Associate Professor, 大学院・医学系研究院, 助教授 (00235681)
ICHIKAWA Kazuhiro  Graduate school, Faculty of Pharmaceutical Sciences, Kyushu University, Research Associate, 大学院・薬学研究院, 助手 (10271115)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥11,600,000 (Direct Cost: ¥11,600,000)
Keywordsin vivo ESR-CT / free-radical / spin-probe / reactive oxygen species / reactive nitrogen species / redox balance / failing myocardium / スピンプローブ / 活性酸素種 / 心筋梗塞 / 拡張型心筋症
Research Abstract

Failing myocardium is a final stage of several types of heart diseases, and the prognosis is the similarly worst as malignant tumor. Therefore, an establishment of preventive method should be essential. Recently, participation of free radicals belonging to reactive oxygen species and reactive nitrogen species in the induction and development of failing myocardium through in vivo cross-talk among free radicals and collapse of redox balance was indicated.
In order to evaluate the fluctuation of redox balance in individuals, it is best way to evaluate temporal-spatial fluctuation of free radical reactions by imaging techniques. In our latest study, we established in vivo ESR-CT system using nitroxyl spin probes, and applied it to non-invasive evaluation of free radical reactions in living mice with several types of diseases. This technique is usable for elucidating a correlation between free radical reactions and failing myocardium in individual organism level and molecular level.
In the present study, we examined a participation of free radicals in the induction and development of failing myocardium using model dogs. As a result, we proved that free radical generation was significantly enhanced, while activities of anti-oxidant enzymes did not fluctuated. Through this experiment, we elucidated that electron transfer system in mitochondria is a main source of these free radicals. In fact, there is a significantly negative correlation between the regeneration of transplanted heart and the degree of free radical generation. On the other hand, we established a novel algorithm for imaging of free radicals in individual, and succeeded to simultaneously determined reactive oxygen species and reactive nitrogen species.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Han J-Y, Takeshita K, Ustumi H.: "Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles"Free Rad. Biol. Med.. 30. 516-525 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ide T, Tsutsui H, Hayashidani S., Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N, Takeshita A.: "Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction"Circ. Res.. 88. 529-535 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Kinugawa S, Suematsu N, Utsumi H, Takeshita A.: "Effects of ACE inhibition on left ventricular failure and oxidative stress in Dahl salt-sensitive rats"J Cardiovasc Pharmacol^<TM>. 37. 725-733 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Suematsu N, Shiomi T, Wen J, Nakamura K, Ichikawa K, Utsumi H, Takeshita A.: "Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure"Circulation. 104. 134-136 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Suematsu N, Utsumi H, Nakamura R, Egarashi K, Takeshita A.: "Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury"Cardiovasc Res.. 49. 103-109 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Han J-Y, Takeshita K and Ustumi H.: "Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles"Free Rad. Biol. Med.. 30. 516-525 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N and Takeshita A.: "Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction"Circ. Res.. 88. 529-535 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Suematsu N, Utsumi H, Nakamura R, Egashira K, Takeshita A.: "Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury"Cardiovasc Res.. 49(1). 103-109 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Suematsu N, Shiomi T, Wen J, Nakamura K, Ichikawa K, Utsumi H and Takeshita A.: "Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure"Circulation. 104. 134-136 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Suematsu N, Utsumi H, Nakamura R, Egarashi K and Takeshita A.: "Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury"Cardiovasc Res.. 49. 103-109 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Han J-Y, Takeshita K, Ustumi H.: "Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles"Free Rad. Biol. Med.. 30. 516-525 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N, Takeshita A.: "Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction"Circ. Res.. 88. 529-525 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Kinugawa S, Suematsu N, Utsumi H, Takeshita A.: "Effects of ACE inhibition on left ventricular failure and oxidative stress in Dahl salt-sensitive rats"J Cardiovasc Pharmacol^<TM>.. 37. 725-733 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Suematsu N, Shiomi T, Wen J, Nakamura K, Ichikawa K, Utsumi H, Takeshita A.: "Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure"Circulation.. 104. 134-136 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsui H, Ide T, Hayashidani S, Suematsu N, Utsumi H, Nakamura R, Egarashi K, Takeshita A.: "Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury"Cardiovasc Res.. 49. 103-109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsumoto K,Utsumi H.: "Development of separable electron spin resonance-computed tomography imaging for multiple radical species : An application to・OH and・NO."Biophysical Journal. 79. 3341-3349 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inoguchi T,Li P,Umeda F,Yu HY,Kakimoto M,Imamura M,Aoki T,Etoh T,Hashimoto T,Naruse M,Sano H,Utsumi H,Nawata H.: "High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD (P) H oxidase in cultured vascular cells."Diabetes. 49. 1939-1945 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinugawa S,Tsutsui H,Hayashidani S,Ide T,Suematsu N,Satoh S,Utsumi H,Takeshita A.: "Treatment with dimethylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice : Role of oxidative stress."Circulation Research. 87. 392-398 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sano H,Naruse M,Matsumoto K,Oi T,Utsumi H.: "A new nitroxy-probe with retention in the brain and its application for brain imaging."Free Radical Biology & Medicine. 28. 959-969 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsumoto K,Endo K,Utsumi H.: "In vivo electron spin resonance assessment of decay constant of nitroxyl radical in selenium-deficient rat."Biological Pharmaceutical Bulltin. 23. 641-644 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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