Potential effects of PKC or protease inhibitors on acute pancreatitis-induced tissue injury in rats

Background: Acute pancreatitis (AP) is still one of the severe diseases, that cause the development of multiple organ dysfunction with a high mortality. Effective therapies for AP are still limited, mainly due to unclear mechanisms by which A-P initiates both pancreatic and extrapancreatic organ injury. Methods: Protease inhibitors (aprotinin, pefabloc, trypsin inhibitor) and PKC inhibitors (polymyxin B, staurosporine) were administrated 30 min before 'induction of AP in rats. To investigate the pancreatic, systemic and lung inflammatory response and injury, plasma IL-6 and IL-10, pancreatic and pulmonary myeloperoxidase (NIPO) levels, pancreatic protease activity and phospholipase A(2) (PLA(2)) activity in ascites were measured 3 and 6 h after AP induction. Results: Pretreatment with protease inhibitors significantly prevented from AP-increased plasma levels of IL-10, pancreatic and pulmonary levels of MTO, pancreatic protease activity and the catalytic activity of PLA(2) in ascites. PKC inhibitors significantly reduced pancreatic and pulmonary levels of MTO and pancreatic protease activity. Conclusion: Inhibition of proteases in AP may be helpful in ameliorating the inflammatory reaction in both pancreatic and extrapancreatic tissues, where neutrophil involvement may be regulated by PKC and proteases. (c) 2007 Elsevier Inc. All rights reserved.