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Development of non-invasive evaluation of oxidative stress against living organisms by in vivo ESR

Research Project

Project/Area Number 10357021
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Physical pharmacy
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

OZAWA Toshihiko  National Institute of Radiological Sciences, 理事 (40160858)

Co-Investigator(Kenkyū-buntansha) UTSUMI Hideo  Kyushuu University, Phamaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (20101694)
NAGANO Tetsuo  University of Tokyo, Pharmacutical Sciences, Professor, 大学院・薬学研究科, 教授 (20111552)
SHIMAMOTO Norio  Takeda Pharmacutical Co., Senior Researcher, 主席部員
MASUMIZU Tosiki  JEOL Co., Researcher, 主任
TAKESHITA Keizo  National Inst.Radiol.Sci., Redox Research, Researcher, レドックス制御研究グループ, 研究員 (70175438)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥32,240,000 (Direct Cost: ¥30,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2001: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2000: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1999: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1998: ¥15,200,000 (Direct Cost: ¥15,200,000)
KeywordsL-band ESR / oxidative stress / trapping agent / nitric oxide (NO) / reactive oxygen species / mouse / nitroxyl radical / ESR imaging / X-バンドESR / フリーラジカル / 重粒子線 / スピンクリアランス / 放射線
Research Abstract

1)New trapping agents for nitric oxide(NO) were developed and their function was elucidated. Further, using these trapping agents NO was detected directly in living animals exposed by whole-body X-irradiation.
2)It was shown that oxidative stress due to X-irradiation could be non-invasively evaluated in living animals by L-band ESR.
3)As a novel nitroxyl probe, acetoxymethyl derivative of Carboxy-PROXYL which can be remained in the brain was developed. This new probe could be well distributed into the mouse brain than other probes. Further, imaging analyzer using ESR-CT method showed that this new probe could be gathered in the brain.
4)A method of separable ESR-CT (electron spin resonance-computed tomography) imaging for multiple radical species was developed and applied to imaging of hydroxyl radical (OH) and nitric oxide (NO). As the result, the position and size of the individual images of OH and NO were in very good agreement with the findings for the sample.
5)A simple and sensitive assay and a cellular bioimaging of a novel diaminofluorescein DAF-FM (3-amino-4-(N-methylamino)-2',7' -difluororescein) and its diacetate. It was found that this novel diaminofluorescein fluorometry should be useful not only for sensitive NO assay, but also for NO imaging in a variety of biological speciemens.
6)In vivo electron spin resonance(ESR) imaging was applied to living mice after peroral administration of a nitroxide radical spin probe. A 3D ESR imaging procedure was applied in vivo in order to obtain the exact distribution of the spin probe in a living animal. The imaging pictures demonstrated that the administered spin probe was firstly located in the stomach, then delivered to the lliver, kidney and heart of the animal.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (36 results)

All 2001 Other

All Journal Article (12 results) Publications (24 results)

  • [Journal Article] Relationship between effects of phenolic compounds on the generation of free radicals from lactoperoxidase-catalyzed oxidation of NAD(P)H or GSH and their DPPH scavenging ability.2001

    • Author(s)
      Jun-ichi Ueda
    • Journal Title

      Chem.Pharm.Bull. 49

      Pages: 299-304

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Dose and Time Dependence of Radiation-induced Nitric Oxide Formation in Mice as Quantified with Electron Paramagnetic Resonance.2001

    • Author(s)
      Hidehiko Nakagawa
    • Journal Title

      Nitric Oxide 5

      Pages: 47-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Pathophysiological Significance of In Vivo ESR Signal Decay in Brain Damage Caused by X-irradiation-Radiation Effect on Nitroxyl Decay of Lipophilic Spin Probe in Head Region-.2001

    • Author(s)
      Yuri Miura
    • Journal Title

      Biochim.Biophys.Acta 1525

      Pages: 167-172

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Quantitative comparison of two types of planar lipid bilayers-forded and Painted-with respect to fusion with vesicles.2001

    • Author(s)
      Kazunori Anzai
    • Journal Title

      J.Biochem.Biophys.Methods 48

      Pages: 283-291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Overexpression of Mitochondrial Manganese Superoxide Dismutase Protects against Radiation-induced Cell Death in the Human Hepatocellular Carcinoma Cell Line HLE.2001

    • Author(s)
      Shigeatsu Motoori
    • Journal Title

      Cancer Res. 61

      Pages: 5382-5388

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Noninvasive Detection of Hydroxyl Radical Generation in Lung by Diesel Exhaust Particles.2001

    • Author(s)
      Jin-Yi Han
    • Journal Title

      Free Radic.Biol.Med. 30

      Pages: 516-525

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Relationship Between Effects of Phenolic Compounds on the Generation of Free Radicals from Lactoperoxidase-catalyzed Oxidation of NAD(P)H or GSH and Their DPPH Scavenging Ability2001

    • Author(s)
      Jun-ichi Ueda, Yuki Tsuchiya, Toshihiko Ozawa
    • Journal Title

      Chem.Pharm.Bull. 49

      Pages: 299-304

    • NAID

      110003615891

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Dose and Time Dependence of Radiation-induced Nitric Oxide Formation in Mice as Quantified with Electron Paramagnetic Resonance2001

    • Author(s)
      Hidehiko Nakagawa, Nobuo Ikota, Toshihiko Ozawa, Yashige Kotake
    • Journal Title

      Nitric Ocide 5

      Pages: 47-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Pathophysiological Significance of In Vivo ESR Signal Decay in Brain Damage Caused by X-irradiation-Radiation Effect on Nitroxyl Decay of Lipophilic Spin Probe in Head Region2001

    • Author(s)
      Yuri Miura, Kazunori Anzai, Jun-ichi Ueda, Toshihiko Ozawa
    • Journal Title

      Biochim.Biophys.Acta 1555

      Pages: 167-172

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Quantitative Comparison of Two Types of Planar Lipid Bilayers-forded and painted-with Respect to Fusion With Vesicles2001

    • Author(s)
      Kazunori Anzai, Kunitake Ogawa, Toshihiko Ozawa, Haruhiko Yamamoto
    • Journal Title

      J.Biochem.Biophys.Methods 48

      Pages: 283-291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Overexpression of Mitochondorial Manganese Superoxide Dismutase Protects against Radiation-induced Cell Death in the Human Hepatocellular Carcinoma Cell Line HLE2001

    • Author(s)
      Shigeatsu Motoori, Hideyuki J.Majima, Masaaki Ebara, Hirotoshi Kato, Futoshi Hirai, Shizuko Kakinuma, Chizuru Yamaguchi, Toshihiko Ozawa, Tetsuo Nagano, Hirohiko Tsujii, Hiromitsu Saisho
    • Journal Title

      Cancer Res. 61

      Pages: 5382-5388

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Noninvasive Detection of Hydroxyl Radical Generation in Lung by Diesel Exhaust Particles2001

    • Author(s)
      Jin-Yi Han, Keizo Takeshita, Hideo Utsumi
    • Journal Title

      Free Radical Biol.Med. 30

      Pages: 516-525

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jun-ichi Ueda: "Relationship between effects of phenolic compounds on the generation of free radicals from lactoperoxidase-catalyzed oxidation of NAD(P)H or GSH and their DPPH scavenging ability"Chem. Pharm. Bull.. 49. 299-304 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hidehiko Nakagawa: "Dose and Time Dependence of Radiation-induced Nitric Oxide Formation in Mice as Quantified with Electron Paramagnetic Resonance"Nitric Oxide. 5. 47-52 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuri Miura: "Pathophysiological Significance of In Vivo ESR Signal Decay in Brain Damage Caused by X-irradiation-Radiation Effect on Nitroxyl Decay of Lipophilic Spin Probe in Head Region-"Biochim. Biophys. Acta. 1525. 167-172 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazunori Anzai: "Quantitative comparison of two types of planar lipid bilayers-forded and Painted-with respect to fusion with vesicles"J. Biochem. Biophys. Methods. 48. 283-291 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shigeatsu Motoori: "Overexpression of Mitochondrial Manganese Superoxide Dismutase Protects against Radiation-induced Cell Death in the Human Hepatocellular Carcinoma Cell Line HLE."Cancer Res.. 61. 5382-5388 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jin-Yi Han: "Noninvasive Detection of Hydroxyl Radical Generation in Lung by Diesel Exhaust Particles"Free Radic. Biol. Med.. 30. 516-525 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuri Miura: "Non-invasive study of radiation-induced oxidative damage using in vivo ESR."Free Radical Biology and Medicine. 28. 854-859 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuri Miura: "Novel Approach to In Vivo Screening for Radioprotective Activity in Whole Mice"Journal of Radiation Reserch. 41. 103-111 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hidehiko Nakagawa: "Induction of superoxide in glioma cell line U87 stimulated with Lipopolysaccharide and interferon-γ : ESR using a new flow-type quartz cell"FEBS Letters. 471. 187-190 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Keizo Takeshita: "Singlet Oxygen-Dependent Hydroxyl Radical Formation during Uroporphyrin-Mediated Photosensitization in the Presence of NADPH"Antioxidants & Redox Signaling. 2. 355-362 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hidehiko Nakagawa: "Dose and Time Dependence of Radiation-induced Nitric Oxide Formation In Mice as Quantifield with Electron Paramagnetic Resonance"Nitric Oxide. 5. 47-52 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuri Miura: "Pathophysiological Significance of In vivo ESR Signal Decay in Brain Damage Caused by X-Irradiation -Radiation Effect on Nitroxyl Decay of Lipophilic Spin Probe in Head Region-"Biochimica Biophysica Acta. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hidehiko Nakagawa: "Scavengers for peroxynitrite : Inhibition oy tyrosine nitration and oxidation with tryptamine,α-1ipoic acid and synthetic compounds"Chemical and Pharmaceutical Bulletin. 48. 261-265 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Osami Yukawa: "Induction of radical scavenging ability and protection against radiation -induced damage to microsomal membranes following low-dose irradiation"International Journal of Radiation Biology. 75. 1189-1199 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hidehiko Nakagawa: "Endogeneous and new synthetic antioxidants for peroxynitrite : selective inhibitory effect of 5-methoxytryptamine and lipoic acid on tyrosine nitration by peroxynitrite"Antioxidants & Redox Signaling. 1. 239-244 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jun-ichi Ueda: "Oxidation of linoleic acid by copper(1 1) complexes : effects of ligand"Journal of Inorganic Biochemistry. 76. 55-62 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazunori Anzai: "Oxidation-dependent changes in the stability and permeability of lipid bilayers"Antioxidants & Redox Signaling. 1. 339-347 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuri Miura: "Non-invasive study of radiation-induced oxidative damage using in vivo ESR"Free Radical Biology and Medicine. (In press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hidehiko Nakagawa: "Spin Trapping for Nitric Oxide Produced in LPS-Treated Mouse Using Various New Dithiocarbamate Iron Complexes Having Substituted Proline and Serine Moiety." Biochemistry Molecular Biology International. 45. 1129-1138 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jun-ichi Ueda: "Reactive Oxygen Species Generated from the Reaction of Copper(II)Complexes with Biological Reductants Cause DNA Strand Scission." Archives Biochemistry Biophysics. 357. 231-239 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kazunori Anzai: "Effects of Hydroxyl Radical and Sulfhydryl Reagents on the Open Probability of the Purified Cardiac Ryanodine Receptor Channel Incorporated into Planar Lipid Bilayers." Biochem.Biophys.Res.Commun.249. 938-942 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kazunori Anzai: "In vitro Studies of the Antioxidant Activity of EPC-K1,A Conjugate of Vitamin C and Vitamin E." Res.Commun.Biochem.Cell & Mol.Biol.2. 129-138 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Sano: "Oxidative Stress Measurement by in vivo Electron Spin Resonance Spectroscopy in Rats with Spreptozocin-Induced Diabetes" Diabetologia. 41. 1355-1360 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirotatsu Kojima: "Detection and Imaging of Nitric Oxide with Novel Fluorescent Indicators:Diaminofluoresceins" Analytical Chemistry. 70. 2446-2453 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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