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

• Published in: International journal of pancreatology 1998-12, Vol.24 (3), p.193-202
• Main Authors: LÜTHEN, R, GRENDELL, J. H, NIEDERAU, C, HÄUSSINGER, D
• Format: Article
• Language: English
• Subjects: Acute Disease; Adenosine Triphosphate - metabolism; Animals; Biliary Tract Diseases - complications; Biological and medical sciences; Disease Models, Animal; Enzyme Activation; Gastroenterology. Liver. Pancreas. Abdomen; Glutathione - metabolism; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Other diseases. Semiology; Pancreas - injuries; Pancreas - metabolism; Pancreatitis - etiology; Pancreatitis - metabolism; Rats; Rats, Sprague-Dawley; Serine Endopeptidases - metabolism; Trypsin Inhibitors - metabolism; Trypsinogen - metabolism
• ISSN: 0169-4197; 2363-5134
• DOI: 10.1007/BF02788422

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 parenchymal injury. It is accompanied by a critical spending of protease inhibitors and glutathione, compromising important acinar cell defense and maintenance mechanisms. 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. 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 gamma-glutamyl transferase (gamma GT) were assessed. Histopathology and elevated activity of gamma GT 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.