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

Conclusion. In models of biliary acute pancreatitis, which might resemble t he situation in humans, premature activation of trypsinogen inside the panc reas ("autodigestion") occurs and is correlated with the extent of ductal a nd parenchymal 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 profou nd 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 var ious severity were induced in rats-ligation of the common bile-pancreatic d uct, retrograde infusion of electrolyte, or retrograde infusion of taurocho late solution-and were compared to sham-operated animals. Trypsin, trypsin inhibitory capacity (TIC), reduced glutathione (GSH), and other compounds w ere measured in pancreatic tissue. Histopathology, as well as serum amylase , lipase, and gamma-glutamyl transferase (gamma GT) were assessed. Results, Histopathology and elevated activity of gamma GT in the serum reve aled increasing severity of pancreatic injury from sham operation through r etrograde duct infusion with taurocholate. GSH was diminished even in macro scopically normal-appearing tissue, but significantly lower in altered (hem orrhagic)-looking sections. Conversely, tissue levels of trypsin were signi ficantly increased. TIC was elevated only in the duct obstruction model, wh ereas it was reduced in the retrograde duct infusion models.