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2000 Fiscal Year Final Research Report Summary

Development of non-invasive system for the evaluation of free radicals in brain with encephalopathy.

Research Project

Project/Area Number 11557173
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Physical pharmacy
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) SANO Hiroaki  Daiichi Radioisotope Laboratories, Ltd. Researcher, 研究員
MASUMIZU Toshiki  JEOL Ltd. Application & Research Center Researcher, 分析機器技術本部, 主任研究員
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) 1999 – 2000
Keywordsin vivo ESR / spin-probe / free-radical / reactive oxygen species / reactive nitrogen species / brain / ischemia-reperfusion / redox balance
Research Abstract

Recently, some studies indicated that free radicals including reactive oxygen species (ROS) and reactive nitrogen species (RNS) associates with a collapse of redox balance in vivo, resulted in induction of several types of diseases. On the contrary, there were few studies on the association of free radicals with encephalopathy in an individual subject, because of a lack of technique, by which redox balance in brain was estimated noninvasively. In the present study, we established a novel technique to noninvasively estimate free radical reactions in brain by using the combination of in vivo ESR and a spin-probe method.
In order to estimate free radical reactions and image them in the brain of living animals, a nitroxyl spin-probe, carboxy-PROXYL acetoxymethyl ester (CxP-AM) was newly synthesized. CxP-AM was designed to be hydrolyzed by esterase, but not by lipase, so that it would pass through the blood-brain barrier and be retained in the cytosolic phase of parenchymal cells in the brain after intravenous injection. The retentivity of the probe in brain was proved through an electron spin resonance computed tomographic imaging technique. Furthermore, we applied this probe to the evaluation of free radical reactions in brain with ischemia-reperfusion. Through these studies, it is elucidated that free radical reactions in the brain with ischemia-reperfusion are significantly enhanced.
The goal of our study is to establish a novel technique for the non-invasive evaluation of redox balance in brain, and apply a new biological parameter on redox metabolism to brain.

  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Han JY,Takeshita K,Utsumi H.: "Diesel exhaust particles actually induce hydroxyl radical formation in the lung of living mice."Free Radical Biological Medicine. 30. 516-525 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [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."Cardiovascular Research. 49. 103-109 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsumoto K,Endo K,Utsumi H.: "In vivo electron spin resonance assessment of decay constant of nitroxy radical in selenium-deficient rat."Biological Pharmaceutical Bulltin. 23. 641-644 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井手友美,筒井裕之,康東天,内海英雄,竹下彰: "電子スピン共鳴法(ESR)を用いた不全心における酸素ラジカルの証明"フリーラジカルの臨床. 15. 55-60 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ide T,Tsutsui H,Hayashidani S,Kang D,Kasai H,Suematsu N,Wen J,Utsumi H.: "8-Oxo-dGTPase, a repair enzyme of oxidative stress-induced DNA damage, is increased in the mitochondria from failing heart."Circulation. 102. 600 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsutsui H,Ide T,Kinugawa S,Takeshita A,Utsumi H.: "Effects of amiodarone on heart cells-Response."Circulation. 102. E170 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ide T,Tsutsui H,Kinugawa S,Suematsu N,Hayashidani S,Ichikawa K,Utsumi H,Machida Y,Egashira K,Takeshita A.: "Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium."Circulation Research.. 86. 152-157 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito S,Yanagishita T,Aoki S,Koba S,Iwata T,Ishioka H,Arata H,Mukae S,Geshi E,Konno N,Katagiri T,Utsumi H.: "Generation of free radicals and the damage done to the sarcoplasmic reticulum during reperfusion injury following brief ischemia in the canine heart."Japan Cirrculation Journal. 63. 373-378 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuda S,Watanabe S,Kobayashi T,Hata N,Misawa Y,Utsumi H,Okuyama H.: "Dietary docosahexaenoic acid enhances ferric nitrilotriacetate-induced oxidative damage in mice but not when additional □-tocopherol is supplemented."Free Radical Research. 30. 199-205 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高城徳子,竹下啓蔵,平田拓,小野光弘,内海英雄: "ポルフィリン症モデルマウスの光照射により皮膚で生じるラジカル反応のin vivo ESR解析"核磁気共鳴と医学. 10. 135-138 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeshita K,Hamada A,Utsumi H: "Mechanisms related to reduction of radical in mouse lung using an L-band ESR spectrometer."Free Radical Biological Medicine. 26. 951-960 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Phumala N,Ide T,Utsumi H.: "Noninvasive evaluation of in vivo free radical reactions catalyzed by iron using in vivo ESR spectroscopy."Free Radical Biological Medicine. 26. 1209-1217 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ide T,Tsutsui H,Kinugawa S,Utsumi H,Takeshita A.: "Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action."Circulation. 100. 690-692 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ide T,Tsutsui H,Kinugawa S,Utsumi H,Kang D,Hattori N,Uchida K,Arimura Ki,Egashira K,Takeshita A.: "Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium."Circulation Research. 85. 357-363 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Han JY.Takeshita K, Utsumi H.: "Diesel exhaust particles actually induce hydroxyl radical formation in the lung of living mice."Free Radic Biol Med.. 30. 516-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Publications] Matsumoto K, Utsumi H.: "Development of separable electron spin resonance-computed tomography imaging for multiple radical species : An application to OH and NO."Biophys J.. 79(6). 3341-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsumoto K, Endo K, Utsumi H.: "In vivo electron spin resonance assessment of decay constant of nitroxy radical in selenium-deficient rat."Biol. Pharm. Bull.. 23. 641-644 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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(11). 1939-45 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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."Circ Res.. 87(5). 392-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sano H, Naruse M, Matsumoto K, Oi T, Utsumi H: "A new nitroxyl-probe with high retention in the brain and its application for brain imaging."Free Radic Biol Med.. 28(6). 959-69 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ide T, Tsutsui H, Kinugawa S, Suematsu N, Hayashidani S, Ichikawa K, Utsumi H, Machida Y, Egashira K, Takeshita A.: "Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium."Circ Res.. 86(2). 152-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito S, Yanagishita T, Aoki S, Koba S, Iwata T, Ishioka H, Arata H, Mukae S, Geshi E, Konno N, Katagiri T, Utsumi H.: "Generation of free radicals and the damage done to the sarcoplasmic reticulum during reperfusion injury following brief ischemia in the canine heart."Jap. Cirrcul. J.. 63(5). 373-378 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasuda S, Watanabe S, Kobayashi T, Hata N, Misawa Y, Utsumi H, Okuyama H.: "Dietary docosahexaenoic acid enhances ferric nitrilotriacetate-induced oxidative damage in mice but not when additional α-tocopherol is supplemented."Free Rad. Res.. 30(3). 199-205 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takajyo T, Takeshita K, Hirata H, Ono M, Utsumi H.: "In vivo ESR measurement of radical reaction in skin of porphyria model mouse under light irradiation."Magnetic Resonance in Medicine. 10. 135-138 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeshita K, Hamada A, Utsumi H.: "Mechanisms related to reduction of radical in mouse lung using an L-band ESR spectrometer."Free Radic Biol Med.. 26(7-8). 951-960 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Phumala N, Ide T, Utsumi H.: "Noninvasive evaluation of in vivo free radical reactions catalyzed by iron using in vivo ESR spectroscopy."Free Radic Biol Med.. 26(9-10). 1209-1217 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ide T, Tsutsui H, Kinugawa S, Utsumi H, Takeshita A.: "Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action."Circulation.. 100(7). 690-692 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ide T, Tsutsui H, Kinugawa S, Utsumi H, Kang D, Hattori N, Uchida K, Arimura Ki, Egashira K, Takeshita A.: "Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium."Circ Res.. 85(4). 357-363 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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