title: Potential effects of PKC or protease inhibitors on acute pancreatitis-induced tissue injury in rats.
abstract: 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 AP 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 (MPO) 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 MPO, pancreatic protease activity and the catalytic activity of PLA(2) in ascites. PKC inhibitors significantly reduced pancreatic and pulmonary levels of MPO and pancreatic protease activity.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Clinical Sciences, Lund University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Changbin
authors.initials: C
authors.lastname: Shi
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Liming
authors.initials: L
authors.lastname: Zhao
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001202:Ascitic Fluid / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D016753:Interleukin-10 / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010447:Peptide Hydrolases / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D013657:Taurodeoxycholic Acid; D013997:Time Factors; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D013450:Sulfones; D014361:Trypsin Inhibitors; D016753:Interleukin-10; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D013657:Taurodeoxycholic Acid; D007611:Aprotinin; D009195:Peroxidase; D011493:Protein Kinase C; D010741:Phospholipases A; D010447:Peptide Hydrolases; D019311:Staurosporine; D011112:Polymyxin B