Glutathione monoethyl ester ameliorates caerulein-induced pancreatitis in the mouse

J Clin Invest. 1992 Jan;89(1):109-16. doi: 10.1172/JCI115550.

Abstract

Studies in animal models suggest that oxygen radicals may be important in the pathogenesis of acute pancreatitis. Because glutathione is an essential component of the defense against radical-mediated cellular injury, we investigated whether pancreatic glutathione content is influenced by inducing acute pancreatitis and whether augmenting the intracellular supply of glutathione would alter the course of pancreatitis. Caerulein, a decapeptide cholecystokinin analogue, induces acute necrotizing pancreatitis in mice when given in high doses (50 micrograms/kg per h) over a period of 6 h. The pancreatic glutathione content (total, GSH + GSSG) in mice treated with high-dose caerulein fell to 17% of normal within 4 h of beginning caerulein and recovered toward normal after discontinuing caerulein treatment. Mice treated with glutathione monoethyl ester (20 mmol/kg 1 h before caerulein, 10 mmol/kg 3 and 7 h after starting caerulein) were found to have blunted depletion of pancreatic glutathione, diminished histologic evidence of pancreatitis (necrosis, inflammation, and vacuolization), and lower serum amylase values compared with mice treated with caerulein alone. These findings suggest that the profound depletion of pancreatic glutathione caused by hyperstimulation of the pancreas with caerulein is critically important in the pathogenesis of acute caerulein-induced pancreatitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amylases / blood
  • Animals
  • Ceruletide
  • Cholecystokinin / analogs & derivatives
  • Disease Models, Animal
  • Female
  • Free Radicals / metabolism
  • Glutathione / analogs & derivatives*
  • Glutathione / analysis
  • Glutathione / pharmacology
  • Isoxazoles / pharmacology
  • Mice
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Pancreatitis / pathology
  • Radiation-Protective Agents / pharmacology*
  • gamma-Glutamyltransferase / metabolism

Substances

  • Free Radicals
  • Isoxazoles
  • Radiation-Protective Agents
  • S-ethyl glutathione
  • Ceruletide
  • Cholecystokinin
  • gamma-Glutamyltransferase
  • Amylases
  • Glutathione
  • acivicin