An inhaled inducible nitric oxide synthase inhibitor reduces damage of Candida-induced acute lung injury

DOI 被引用文献1件 参考文献46件
  • OHSUGI Shuji
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • IWASAKI Yoshinobu
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • TAKEMURA Yoshizumi
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Research Center for Respiratory Cell Engeering, Doshisha University
  • NAGATA Kazuhiro
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • HARADA Hidehiko
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • YOKOMURA Ichiro
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • HOSOGI Shigekuni
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • YUBA Tatsuya
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • NIISATO Naomi
    Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • MIYAZAKI Hiroaki
    Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • MATSUBARA Hiroaki
    Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • FUSHIKI Shinji
    Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • MARUNAKA Yoshinori
    Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

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抄録

Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxynitrite. We previously showed by immunostaining that the expression of iNOS was suppressed by inhalation of NG-nitro-L-arginine methyl ester in mice with Candida-induced ALI. This study tested the hypothesis that a novel iNOS inhibitor suppresses not only iNOS expression, but also iNOS messenger RNA (mRNA) production by interrupting a positive feedback loop at the time of NO production in Candida-induced ALI. Mice were pretreated by inhalation of saline or ONO-1714, a selective iNOS inhibitor, and were given an intravenous injection of Candida albicans to induce ALI. After inhalation of 1 mM aerosolized ONO-1714, the nitrite-nitrate concentration in bronchoalveolar lavage fluid (BALF) at 24 h was significantly lower than that after inhalation of saline. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and neutrophils in BALF were decreased by inhalation of ONO-1714. Inhalation of ONO-1714 markedly suppressed nitrotyrosine production and inhibited the expression of iNOS mRNA as well as proteins in the lung. Survival was prolonged by inhalation of ONO-1714. We conclude that pretreatment with inhaled ONO-1714 suppresses the production of peroxinitrite and decreases oxidative stress associated with peroxinitrite in Candida-induced ALI.

収録刊行物

  • Biomedical Research

    Biomedical Research 28 (2), 91-99, 2007

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