Inhibition of nuclear factor-κB activation improves the survival of rats with taurocholate pancreatitis

A. Satoh, T. Shimosegawa, M. Fujita, K. Kimura, A. Masamune, M. Koizumi, T. Toyota

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126 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)253-258
Number of pages6
JournalGut
Volume44
Issue number2
DOIs
Publication statusPublished - 1999

Keywords

  • Macrophages
  • Multiple organ dysfunction
  • Nuclear factor-κB
  • Pancreatitis
  • Pyrrolidine dithiocarbamate
  • Rat

ASJC Scopus subject areas

  • Gastroenterology

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