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-kappaB (NF-kappaB) in macrophages of rats with lethal pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB, on the pathology and mortality. METHODS: Taurocholate pancreatitis was produced in rats, and the severity of the disease, the mortality, and activation of NF-kappaB 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-kappaB was activated in peritoneal and alveolar macrophages six hours after pancreatitis induction. Pretreatment with PDTC dose-dependently attenuated the NF-kappaB 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-kappaB activation may be effective in reducing fatal outcome in severe acute pancreatitis.
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-kappaB (NF-kappaB) in macrophages of rats with lethal pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB, on the pathology and mortality. METHODS: Taurocholate pancreatitis was produced in rats, and the severity of the disease, the mortality, and activation of NF-kappaB 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-kappaB was activated in peritoneal and alveolar macrophages six hours after pancreatitis induction. Pretreatment with PDTC dose-dependently attenuated the NF-kappaB 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-kappaB activation may be effective in reducing fatal outcome in severe acute pancreatitis.
Authors: C Niederau; M Niederau; F Borchard; K Ude; R Lüthen; G Strohmeyer; L D Ferrell; J H Grendell Journal: Pancreas Date: 1992 Impact factor: 3.327
Authors: V Gross; R Andreesen; H G Leser; M Ceska; E Liehl; M Lausen; E H Farthmann; J Schölmerich Journal: Eur J Clin Invest Date: 1992-03 Impact factor: 4.686
Authors: S J Konturek; A Dembinski; P J Konturek; Z Warzecha; J Jaworek; P Gustaw; R Tomaszewska; J Stachura Journal: Gut Date: 1992-09 Impact factor: 23.059
Authors: H G Leser; V Gross; C Scheibenbogen; A Heinisch; R Salm; M Lausen; K Rückauer; R Andreesen; E H Farthmann; J Schölmerich Journal: Gastroenterology Date: 1991-09 Impact factor: 22.682