The effect of synacthen on acute necrotizing pancreatitis in rats

Pancreas. 2008 Oct;37(3):316-20. doi: 10.1097/MPA.0b013e31816fd78a.

Abstract

Objectives: This study investigates the hypothesis that an adrenocorticotropic hormone-analog therapy may ameliorate relative adrenal insufficiency in the early phase of acute necrotizing pancreatitis (NP) by boosting endogenous glucocorticoid production.

Methods: Forty Wistar rats with taurocholate-induced NP were divided into 5 groups: the first group received low-dose Synacthen (0.5 mg/kg); the second, high-dose Synacthen (5mg/kg); the third,low-dose cortisol (10 mg/kg); the fourth, high-dose cortisol (100 mg/kg); and the fifth, the control group, received no treatment. All animals were killed after 6 hours: concentrations of plasma corticosterone, interleukin 1 (IL-1), IL-6, IL-10, tumor necrosis factor alpha, amylase, and lipase in ascites, myeloperoxidase activity in the pancreas, and a histological score were evaluated.

Results: Corticosterone increased neither in the low-dose nor in the high-dose Synacthen group. Synacthen did not improve the early course of NP in terms of laboratory and histological results. A reduction of pancreatic necrosis and inflammation was observed in the low-dose cortisol group.

Conclusions: Endogenous glucocorticoid release seemed to be at its maximum during the early stage of NP and could not be further increased by Synacthen. Low-dose exogenous cortisol ameliorated the disease. These findings support the existence of relative adrenal insufficiency in the early phase of acute NP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Insufficiency / chemically induced
  • Adrenal Insufficiency / drug therapy*
  • Adrenal Insufficiency / metabolism
  • Amylases / metabolism
  • Animals
  • Cosyntropin / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Hydrocortisone / blood
  • Hydrocortisone / pharmacology*
  • Lipase / metabolism
  • Pancreas / drug effects*
  • Pancreas / enzymology
  • Pancreas / pathology
  • Pancreatitis, Acute Necrotizing / chemically induced
  • Pancreatitis, Acute Necrotizing / drug therapy*
  • Pancreatitis, Acute Necrotizing / metabolism
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Taurocholic Acid
  • Time Factors

Substances

  • Cytokines
  • Cosyntropin
  • adrenocorticotropin zinc
  • Taurocholic Acid
  • Peroxidase
  • Lipase
  • Amylases
  • Hydrocortisone