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1987 Fiscal Year Final Research Report Summary

PROTECTION BY ANTOXIDANTS OF ISCHEMIC CELLULAR DAMAGE

Research Project

Project/Area Number 61570139
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionHIROSHIMA UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

KAWASAKI Takashi  Professor of Hiroshima University School of Medicine, 医学部, 教授 (40034011)

Co-Investigator(Kenkyū-buntansha) SHIKATA Hiroo  Research Assistant of Hiroshima University School of Medicine, 医学部, 助手 (10170854)
SUGINO Keizo  Research Assistant of Hiroshima University School of Medicine, 医学部, 助手 (80162882)
YAMADA Kazuo  Associate Professor of Hiroshima University School of Medicine, 医学部, 助教授 (00093831)
Project Period (FY) 1986 – 1987
KeywordsIschemic cellular damage / Antioxidants / Protection of ischemic organ damage / Endotoxin shock / 虚血肝移植保護
Research Abstract

Liver ischemia-reperfusion induced cellular damage caused by stimulated lipid peroxidation on biomembranes, especialy after reperfusion, which resulted in a marked decrease in ATP resynthesis after reperfusion due to mitochondrial dysfunction, and a decrease in the survival rate depending on ischemic periods. The administration of either coenzyme q_<10> (CoQ_<10>) or <alpha>-tocopherol (<alpha>-Toc) prior to ischemia completely suppressed the stimulated lipid peroxidation, and raised ATP resynthesis due to reversal of the mitochondrial dysfunction, which were accompained by a marked rise in the survival rate from 0% to 60% after 90-min ischemia. When endogenous levels of CoQ_<10> homologs (CoQ_9, CoQ_<10>), <alpha>-Toc and reduced glutathione (GSH) in the liver were determined during 90-min ischemia and following 60-min reperfusion period, the lwvels of <alpha>-Toc and GSH decreased during ischemia, which were not protected by CoQ_<10> pretreatment. The levels of endogenous antioxidant … More s tested decreased markedly after reperfution following to ischemia, which were completely reversed by the administration of either CoQ_<10> or <alpha>-Toc. These results obtained are compatible with the assumption that cellular damage caused by hepatic ischemia-reperfusion can be explained by free radical injury, and that antioxidants administered can protect cellular damage from lipid peroxidation by either radical scavenging and antioxidant actions.
The protective effect of CoQ_<10> on ischemic damage could be demonstrated with orthotopic transplantation of the rat liver subjected to warm ischemia for 30 min: the survival rate of recipient rats increased from 0% to 45% in CoQ_<10>-pretreated group.
Cellular damage due to endotoxemia was also explained, at least in part, by stimulated lipid peroidation. The administration of CoQ_<10> and <alpha>-Toc completely suppressed lipid peroxidation with a marked improvement of energy metabolism as well as endogenous levels of antioxidants, which, resulted in a marked rise of the survival rate. Less

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Marubayashi,S.;Dori,K.;Ohi,K.,& Kawasaki,T.: Surgery. 99. 184-192 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugino,K.;Dohi,K.;Yamada,K.& Kawasaki,T.: Surgery. 101. 746-753 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sumimoto,K.;Inagaki,K.;Marubayashi,S.;Ito,H.;Yamada,K.;Kawasaki,T.,& Dohi,K.: Surgery. 102. 821-827 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sumimoto,K.;Inagaki,K.;Marubayashi,S.;Kawasaki,T.& Dohi,K.: Transplantation Proc.22. (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川崎尚: 代謝. 24. 389-399 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川崎尚: ビタミン. 61. 373-382 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 杉野圭三,山田一夫,土肥雪彦,丸林誠二,川崎尚: 活性酸素. 385 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki,T.;Sugino,K.,& Marubayashi,S.: "Biomedical and Clinical Aspects of Coenzyme Q,vol.5." Elsevier Biomedical Press,Amsterdam,Netherlands, 410 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Marubayashi, S., Dohi, K., Ochi, K., & Kawasaki, T.: "Role of free radicals in ischemic rat liver cell injury: Prevention of damage by <alpha>-tocopherol administration" Surgery. 99. 184-192 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugino, K., Dohi, K., Yamada, K., & Kawasaki, T.: "The role of lipid peroxidation in endotoxin induced-hepatic damage and the protecitve effect of antioxidants" Surgery. 101. 746-753 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sumimoto, K., Inagaki, K., Marubayashi, S., Ito, H., Yamada, K., Kawasaki, T., & Dohi, K.: "Ischemic damage prevention by coenzyme q_<10> treatment of the donor before orthotopic liver transplantation: Biochemical and histologic findings" Surgery. 102. 821-827 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sumimoto, K., Inagaki, K., Marubayashi, S., Kawasaki, T., & Dohi, K.: "Energy metabolism in warm ischemically damaged liver grafts after translantation and protection by coenzyme Q_<10> pretreatment" Transplantation Proc.22. in press (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawasaki, T., Sugino, K., & Marubayashi, S.: Biomedical and Clinical Aspects of Coenzyme Q, vol. 5.Elevier Biomedical Press, Amsterdam, Netherlands, 410 (1986)

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

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Published: 1989-03-30  

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