Trypsinogen activation and glutathione content are linked to pancreatic injury in models of biliary acute pancreatitis

R Lüthen, JH Grendell, C Niederau… - International journal of …, 1998 - Springer
R Lüthen, JH Grendell, C Niederau, D Häussinger
International journal of pancreatology, 1998Springer
Conclusion In models of biliary acute pancreatitis, which might resemble the situation in
humans, premature activation of trypsinogen inside the pancreas (“autodigestion”) occurs
and is correlated with the extent of ductal and parencymal injury. It is accompanied by a
critical spending of protease inhibitors and glutathione, compromising important acinar cell
defense and maintenance mechanisms. Background Premature activation of pancreatic
digestive enzymes and profound changes of levels of certain biochemical compounds have …
Conclusion
In models of biliary acute pancreatitis, which might resemble the situation in humans, premature activation of trypsinogen inside the pancreas (“autodigestion”) occurs and is correlated with the extent of ductal and parencymal injury. It is accompanied by a critical spending of protease inhibitors and glutathione, compromising important acinar cell defense and maintenance mechanisms.
Background
Premature activation of pancreatic digestive enzymes and profound changes of levels of certain biochemical compounds have been implicated in the pathophysiology of acute pancreatitis. Hitherto, little information on their role in biliary acute pancreatitis has been available.
Methods
Three types of injury to the pancreaticobiliary duct system of various severity were induced in rats—ligation of the common bile-pancreatic duct, retrograde infusion of electrolyte, or retrograde infusion of taurocholate solution—and were compared to sham-operated animals. Trypsin, trypsin inhibitory capacity (TIC), reduced glutathione (GSH), and other compounds were measured in pancreatic tissue. Histopathology, as well as serum amylase, lipase, and γ-glutamyl transferase (γGT) were assessed.
Results
Histopathology and elevated activity of γGT in the serum revealed increasing severity of pancreatic injury from sham operation through retrograde duct infusion with taurocholate. GSH was diminished even in macroscopically normal-appearing tissue, but significantly lower in altered (hemorrhagic)-looking sections. Conversely, tissue levels of trypsin were significantly increased. TIC was elevated only in the duct obstruction model, whereas it was reduced in the retrograde duct infusion models.
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