Role of oxygen-derived free radicals in protease activation after pancreas transplantation in the pig.
The role of oxygen-derived free radicals in pancreatitis after pancreas transplantation was examined in a porcine pancreatic transplantation model. Trypsin activation, protease inhibitor consumption, kininogen consumption, and postoperative graft function were investigated in 24 pigs subjected to whole organ pancreaticoduodenal transplantation. The animals were divided into one control group and two groups treated with free radical scavengers. One group was given allopurinol, and one group was treated with superoxide dismutase in combination with catalase. In the early phase (within 1 hr) after reperfusion, no differences were seen between the groups as to protease activation. Neither trypsin-protease inhibitor imbalance nor any signs of kininogen consumption were seen. In a later phase (1-3 days after the transplantation), the trypsin activation, measured as high molecular weight immunoreactive cationic trypsin in plasma, was significantly less pronounced in allopurinol-treated animals. This finding indicates a less severe form of reperfusion pancreatitis in this group compared with the other groups. A tendency toward better function in the allopurinol-treated group was also seen. We conclude that oxygen-derived free radicals seem to be of importance in the development of reperfusion pancreatitis after pancreas transplantation in the pig. We also conclude that allopurinol, but not superoxide dismutase/catalase, possibly due to the administration regimens used in this series, is able to attenuate the trypsin activation and the development of pancreatitis in the later phase in this model.
Petersson
U
U
Department of Surgery, University Hospital MAS, University of Lund, Malmö, Sweden.
Källén
R
R
Montgomery
A
A
Borgström
A
A
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D004386:Duodenum / Q000098:blood supply / Q000637:transplantation*; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006085:Graft Survival; D007413:Intestinal Mucosa / Q000098:blood supply; D007704:Kininogens / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism; D016035:Pancreas Transplantation / Q000502:physiology*; D015424:Reperfusion; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014184:Transplantation, Homologous / Q000502:physiology*; D014357:Trypsin / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007704:Kininogens; D009842:Oligopeptides; D000511:alpha-Macroglobulins; C080396:trypsinogen activation peptide; D000493:Allopurinol; D014362:Trypsinogen; D002374:Catalase; D013482:Superoxide Dismutase; D010450:Endopeptidases; D014357:Trypsin