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1993 Fiscal Year Final Research Report Summary

Analysis of active oxygen metabolism in organ microcirculation using confocal laser microscopy

Research Project

Project/Area Number 04404040
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKEIO University

Principal Investigator

TSUCHIYA Masaharu  Internal Medicine, Keio University Professor, 医学部・内科, 教授 (60051124)

Co-Investigator(Kenkyū-buntansha) SAITO Hidekazu  Internal Medicine Ass.Professor, 医学部・内科, 講師 (80186949)
MIURA Soichiro  Internal Medicine Ass.Professor, 医学部・内科, 講師 (50138012)
Project Period (FY) 1992 – 1993
Keywordsmicrocirculation / confocal laser microscopy / active oxygen / nitric oxide / rhodamine 123 / dichlorofluorescin / propidium iodide / ischemia-reperfusion
Research Abstract

We have established the experimental set up for intravital observation using confocal laser scanning imaging system. Our experiments were performed using fluorescence probes ; dichlorofluorescin diacetate (a fluorochrome sensitive to intracellular hydroperoxide formation), rhodamine 123 (a fluorochrome sensitive to the mitochondrial membrane potential, ) and propidium iodide (which labels the unclei of non viable cells).
By using above mentioned set up ;
1. It has been observed that leukocyte adhesion along postcapillary venules, the oxidative stress and the mitochondrial dysfunction occur in rat mesenteric microcirculation after ischemiareperfusion.
2. Intralobular heterogeneity of the oxidative stress and the mitochondrial dysfunction were visualized in relation to their topographic distributions with the cell death during low-flow hypoxia in perfused liver. The oxidative stress and the resultant cell death during low-fow hypoxia are spatially restricted in the intermediate zone between … More the periportal and pericentral regions.
3. Cold ischemia followed by reperfusion induced leukocyte adhesion to the sinusoidal wall and the damage of parenchymal cells. Superoxide dismutase attenuated these ischemiareperfusion-induced injuries.
4. The metabolic changes in tumor cells after coculturing with Kupffer cells were visualized and analyzed. In cocultured hepatoma cells and colon cancer cells, Kupffer cells induced the oxidative stress and the mitochondrial dysfunction followed by cell death. Superoxide dismutase did not inhibit the mitochondrial dysfunction and cell death. L-NMMA,an inhibitor of nitric oxide production eliminated decrease in mitochondrial energization and the tumor cell injury induced by Kupffer cells. Kupffer cell-derived nitric oxide may present tumor cell cytotoxicity via inhibiting mitochondrial dysfunction.
The metabolic changes in tumor cells were also determined ex vivo perfused liver. The oxidative stress and the mitochondrial dysfunction in tumor cells, which adhered to the liver sinusoid, were also obvious as well as those in vitro experiments. Less

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Iwao Kurose,et al.: "Oxyradical Generation from Leukocytes during Endotoxin-Induced Microcirculatory Disturbance in Rat mesentery-Attenuating Effect of Cetraxate" Toxicology and Applied Pharmacology. 120. 37-44 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao Kurose,et al.: "Fluorographioc Study on the Oxidative Stress in the Process of Gastric Mucosal Injury:Attenuating Effect of VitaminE" Journal of Gastroenterology and Hepatology. 8. 254-258 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao Kurose,et al.: "Nitric Oxide Mediates Kupffer Cell-induced Reduction of Mitochondrial Energization in Hepatoma Cells:A Comparison with Oxidative Burst" Cancer Research. 53. 2676-2682 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao Kurose,et al.: "Nitric oxide Mediates Lipopolysaccharide-induced Alteration of Mitochondrial Function in Cultured Hepatocytes and Isolated perfused Liver" Hepatology. 18. 380-388 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao Kurose,et al.: "Mechanisms of Endothelin-induced Macromolecular Leakage in Microvascular Beds of Rat Mesentery" European Journal of Pharmacology. 250. 85-94 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 福村 大: "Kupffer細胞の抗腫瘍活性におけるnitric oxideの役割" 慶應医学. 70. 877-887 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 福村 大、他: "Cyto-protection & biology Vol.11" 癌と化学療法社, 71-74 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dai Fukumura,et al: "Progress in Microcirculation Research-Selected Proceedings of the First Asian Congress for Microcirculation" ELSEVIER SCIENCELTD(in press),

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao Kurose, et al.: "Oxyradical Generation from Leukocytes during Endotoxin-Induced Microcirculatory Disturbance in Rat mesentery-Attenuating Effect of Cetraxate" Toxicology and Applied Pharmacology. 120. 37-44 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao Kurose, et al.: "Fluorographioc Study on the Oxidative Stress in the Process of Gastric Mucosal Injury : Attenuating Effect of Vitamin E" Journal of Gastroenterology and Hepatology. 8. 254-258 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao Kurose, et al.: "Nitric Oxide Mediates Kupffer Cell-induced Reduction of Mitochondrial Energization in Hepatoma Cells : A Comparison with Oxidative Burst" Cancer Research. 53. 2676-2682 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao Kurose, et al.: "Nitric oxide Mediates Lipopolysaccharideinduced Alteration of Mitochondrial Function in Cultured Hepatocytes and Isolated perfused Liver" Hepatology. 18. 380-388

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao Kurose, et al.: "Mechanisms of Endothelin-induced Macromolecular Leakage in Microvascular Beds of Rat Mesentery" European Journal of Pharmacology. 250. 85-94 (1993)

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

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Published: 1996-04-15  

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