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Inhibition of nuclear factor-κB activation improves the survival of rats with taurocholate pancreatitis
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  1. A Satoh,
  2. T Shimosegawa,
  3. M Fujita,
  4. K Kimura,
  5. A Masamune,
  6. M Koizumi,
  7. T Toyota
  1. Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
  1. Dr T Shimosegawa, Third Department of Internal Medicine, Tohoku University School of Medicine, 1–1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980–77, Japan.

Abstract

Background Death in the early stages of severe acute pancreatitis is frequently the result of multiple organ dysfunction, but its mechanism is not clear.

Aims To investigate the state of nuclear factor-κB (NF-κB) in macrophages of rats with lethal pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate, an inhibitor of NF-κB, on the pathology and mortality.

Methods Taurocholate pancreatitis was produced in rats, and the severity of the disease, the mortality, and activation of NF-κB in peritoneal and alveolar macrophages were compared in rats receiving pyrrolidine dithiocarbamate (PDTC) treatment and those that were not.

Results Taurocholate pancreatitis produced massive necrosis, haemorrhage, and severe leucocyte infiltration in the pancreas as well as alveolar septal thickening in the lung. NF-κB was activated in peritoneal and alveolar macrophages six hours after pancreatitis induction. Pretreatment with PDTC dose-dependently attenuated the NF-κB activation and improved the survival of the rats, although it did not affect the early increase in serum amylase and histological findings.

Conclusions Early blockage of NF-κB activation may be effective in reducing fatal outcome in severe acute pancreatitis.

  • pancreatitis
  • multiple organ dysfunction
  • nuclear factor-κB
  • pyrrolidine dithiocarbamate
  • macrophages
  • rat
  • Abbreviations

    EMSA
    electrophoretic mobility shift assay
    IL
    interleukin
    iNOS
    inducible nitric oxide synthase
    ICAM-1
    intercellular adhesion molecule-1
    MOF
    multisystem organ failure
    NF-κB
    nuclear factor-κB
    PBS
    phosphate buffered saline
    PDTC
    pyrrolidine dithiocarbamate
    TCA
    taurocholate
    TNF
    tumour necrosis factor
    VCAM-1
    vascular cell adhesion molecule-1
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  • Abbreviations

    EMSA
    electrophoretic mobility shift assay
    IL
    interleukin
    iNOS
    inducible nitric oxide synthase
    ICAM-1
    intercellular adhesion molecule-1
    MOF
    multisystem organ failure
    NF-κB
    nuclear factor-κB
    PBS
    phosphate buffered saline
    PDTC
    pyrrolidine dithiocarbamate
    TCA
    taurocholate
    TNF
    tumour necrosis factor
    VCAM-1
    vascular cell adhesion molecule-1
  • View Full Text

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