Inhibition of nuclear factor-kappaB activation improves the survival of rats with taurocholate 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.


OBJECTIVE
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.
Satoh
A
A
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Shimosegawa
T
T
Fujita
M
M
Kimura
K
K
Masamune
A
A
Koizumi
M
M
Toyota
T
T
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016676:Macrophages, Alveolar / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D015996:Survival Rate; D013656:Taurocholic Acid; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D013656:Taurocholic Acid