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2002 Fiscal Year Final Research Report Summary

Study on Development of Redox Regulatative Substances Against Oxidative Stress.

Research Project

Project/Area Number 13672337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

ITOKA Nobuo  National Institute of Radiological Sciences, Redox Regulation Research group, Group Leader, レドックス制御研究グループ, グループリーダ (80159649)

Co-Investigator(Kenkyū-buntansha) NAKAGAWA Hidehiko  National Institute of Radiological Sciences, Redox Regulation Research group, レドックス制御研究グループ, 主任研究員 (80281674)
Project Period (FY) 2001 – 2002
Keywordsoxidative stress / reactive oxygen species / reactive nitrogen species / superoxide / hydroxyl radical / peroxynitrite / antioxidant / redox regulation
Research Abstract

Rective oxygen species such as superoxide, hydroyl radical, and peroxy radical have been implicated in the aging process and in a wide variety of diseases such as cancer. Radiation induced tissue damage is also a direct result of free radical-mediated toxicity. Redox regulation is to maintain the homeostasis in vivo against oxidative stress by regulating redox state. In this study, explorative study on scavenging reactive oxygen species. The scavenging abilities were estimated with ESR spin-trapping method using DMPO as spin-trapping reagent for superoxide and hydroxyl radical, and for peroxyradical, decay of cumylperoxyradical was directry measured with ESR The antioxidants used in this study were the synthetic fluorochalcon, applephenon(extract from apple, polyphenol), vegetables (water soluble conponents), γ-tocotrienol, cathechin derivative, artepillin c(major component of Brajilian propolis), thiol containing compounds such as methionine and penicillamin. uperoxide was generated f … More rom hypoxantine-xantine oxidase system and hydroxyl radical was generated from Cu(en)2-H2O2 system, cumen peroxyl radical was generated from di-tert-butyl peroxide and cumene with a high pressure mercury lamp. Polyphenol derivative such as hydroxylcharcon derivative, applephenone, extravt from eggplant, showed high scavenging ability against hidroxyl radical as potent as gluthathion and trolox. Against superoxide, cathechin derivative and thiol-containing compound showed very high scavenging ability. Artepillin c shows high scavenging ability against peroxyl radical, conparable to (+)-cathechin. Generally, there are two mechanism of hydrogen-transfar reactions from phenolic compounds to radical species, i.e., a one-step hydrogen atom transfer or electron transfer followed by proton transfer. The examination of kinetics of hydrogen transfer for phenolic antioxidants with or without methala such as magnesium or scandium indicated that the hydrogen-transfer reaction of (+)-cathechin proceeds via electron transfer to radicals followed by proton transfer, and hydrogen-transfer reaction of Vitamin E and Artepillin C proceeds via one-step hydrogen atom transfer. protective effects of radioprotector and antioxidants in mice given a lethal dose (8 Gy) of X-ray irradiation was examined. 30 days survival rate for applephenon was 30%(control : 0%), and DRF8dose-reduction factor) afforded by POBN(α-(4-Pyridyl 1 -oxide)-N-tert-butylnitrone) was about 1.3. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Nakagawa, H., Oshima, Y., Takusagawa, M., Ikota, N., et al.: "Functional modification of cytochrome c by proxynitrite in an electorontransfer reaction"Chem.Pharm.bull.. 49. 1547-1554 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kikuchi, Tatsuya, Fukushi, Kiyoshi, Ikota, Nobuo, Irie, Toshiaki, et al.: "Synthesis of Piperidinyl and Pyrrolidinyl Butyrates for In Vivo measurement of Cerebral Butyrylcholine sterase Activity"J.Labelled Cpd.Radiopharm.. 43. 753-765 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakagawa, N.Ikota, T.Ozawa, Y.Kotake: "Dose and time dependence of radiation-induced nitric oxide formation in as quantified with electron paramagnetic resonance"Nitric Oxide : Biology and Chemistry. 5. 47-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikuo Nakanishi, Kentaro Miyazaki, Nobuo Ikota, Toshihiko Ozawa, Shunichi Fukuzumi. et al.: "Effects of Metal Ions Distinguishing Between One-Step Hydrogen-and Electron-Transfer Mechanisms for the Radical-Scavenging Reaction of (+)-Catechin"J.Phys.Chem.A. 106. 11123-11126 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kiyoshi Fukuhara, Ikuo Nakanishi, Kentaro Miyazaki, Naoki Miyata, Nobuo Ikota, Shunichi Fukuzumi et al.: "Planar Catechin Analogue as a Promising Antioxidant with Reduced Prooxidant Activity"Chemical Research Toxicology. 16. 81-86 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikuo Nakanishi, Kentaro Miyazaki, Haruko Yakumaru, Jun-ichi Ueda, Kiyoshi Fukuhara, Shunichi Fukuzumi, Nobuo Ikota et al.: "Efficient Radical-Scavenging Ability of Artepillin C, a Major Component of Brazilian Propolis, and the Mechanism"Org.Biomol.Chem.. 1. 1452-1454 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshikazu Nishimura, Hee-Sun Kim, Nobuo Ikota, Hiromi Arima, Masae Yukawa, Toshihiko Ozawa, et al.: "Radioprotective Efect of Chitosan in Sub-lethally X-ray Irradiated Mice"J.Radiat.Res.. 44. 53-58 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Nakagawa, N. Ikota, and T. Ozawat, Y. Kotake: "Dose and time dependence of radiation-induced nitric oxide formation in as quantified with electron paramagnetic resonance"Nitric Oxide : Biology and Chemistry. 5. 47-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kikuchi, Tatsuya, Fukushi, Kiyoshi, Itota, Nobuo, Ueda, Takao, Nagatsuka. Shin-ichiro, Arano, Yasushi, Irie, Toshiaki: "Synthesis of Piperidinyl and Pyrrolidinyl Butyrates for In Vivo measurement of Cerebral Butyrylcholine sterase Activity"J. Labelled Cpd. Radiopharm.. 43. 753-765 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakagawa, H., Ohshima, Y., Takusagawa, M., Ikota, N., Takabasbi, Y., Shimizu, S., Ozawa, T.: "Functional modification of cytochrome c by peroxynitrite in an electrontransfer reaction"Chem. Pharm. Bull. 49. 1547-1554 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikuo Nakanishi, Kentaro Miyazaki, Tomokazu Shimada, Kei Ohkubo, Shiro Urano, Nobuo Ikota, Toshihiko Ozawa, Shunichi Fukuzumi, Kiyoshi Fukuhara: "Effects of Metal Ions Distinguishing Between One-Step Hydrogen- and Electron-Transfer Mechanisms for the Radical-Scavenging Reaction of (+)-Catechin"J.Phys.Chem. A. 106. 11123-11126 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyoshi Fukuhara, Ikuo Nakanishi, Tomokazu Shimada, Kei Ohkubo, Kentaro Miyazaki, Wataru Hakamata, Shiro Urano, Toshihiko Ozawa, Haruhiro Okubo, Naoki Miyata, Nobuo Ikota, Shunichi Fukuzumi: "A Planar Catechin Analogue as a Promising Antioxidant with Reduced Prooxidant Activity"Chemical Research Toxicology. 16. 81-86 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikuo Nakanishi, Yoshihiro Uto, Kei Ohkubo, Kentaro Miyazaki, Haruko Yakumaru, Shiro Urano, Haruhiro Okuda, Jun-ichi Ueda, Toshihiko Ozawa, Kiyoshi Fukuhara, Shunichi Fukuzumi, Hideko Nagasawa, Hitoshi Hori, Nobuo Itota: "Efficient Radical-Scavenging Ability of Artepillin C, a Major Component of Brazilian Propolis, and the Mechanism"Org. Biomol.Chem.. 1. 1452-1454 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshikazu Nishimura, Hee-Sun Kim, Nobuo Ikota, Hiromi Arima, Hee-Seung Bom, Young-Ho Kim, Yoshito Watanabe, Masae Yukawa, Toshihiko Ozawa: "Radioprotective Effect of Chitosan in Sub-lethally X-ray Irradiated Mice"J.Radiat.Res.. 44. 53-58 (2003)

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

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Published: 2004-04-14  

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