INTRAPANCREATIC ZYMOGEN ACTIVATION AND LEVELS OF ATP AND GLUTATHIONE DURING CERULEIN PANCREATITIS IN RATS

Studies in acutely inflamed pancreatic tissue in humans and animals su ggest that premature activation of proteases within the gland plays a key role in its pathophysiology. The present study aimed to detect suc h protease activation in relation to protease inhibition and to change s in the concentrations of the vital cellular compounds ATP and glutat hione in pancreatic tissue during caerulein-induced pancreatitis in ra ts. Within 1 h after supramaximal stimulation by intraperitoneal caeru lein injection, pancreatic tissue activities of enzymatically active t rypsin and elastase showed significant increases, accompanied by a two fold increase in trypsin inhibitory capacity. Over the same time cours e pancreatic ATP and glutathione concentrations dropped to 38% and 47% , respectively, after 1 h and reached a nadir of 22% and 28%, respecti vely, after 4-8 h. Intrapancreatic trypsin activation in this model, d espite increasing trypsin inhibitory capacity, indicates concealed lib eration of even more protease or enzyme-inhibitor complex instability. It is hypothesized that early acinar glutathione depletion, in part d ue to diminished ATP, could play a role in the premature activation of digestive enzymes by impairment of the integrity of the cytoskeleton and cell organelles or lowered defense capabilities against oxidant st ress, finally leading to acute pancreatitis.