title: Oxygen radical production precedes alcohol-induced acute pancreatitis in rats.
abstract: BACKGROUND
  Ethanol is involved in approximately 40% of the cases of acute pancreatitis.
  
  
  OBJECTIVE
  To investigate the influence of ethanol on the pancreatic generation of oxygen-free radicals (OFR) in alcohol-induced acute pancreatitis as one possible pathway of proenzyme activation in this disease.
  
  
  METHODS
  In one model of acute pancreatitis, the combination of ethanol with mild stimulation of the pancreas and short-term duct obstruction leads to acute pancreatitis within 24 hours. Pancreatic tissue and blood samples were assessed for reduced (GSH) and oxidized (GSSG) glutathione, malondialdehyde, conjugated dienes (CD), and myeloperoxidase. The histologic development of the acute pancreatitis was followed between 0.5 and 24 hours.
  
  
  RESULTS
  Ethanol systemically decreased the radical defense system (GSSG: control 0.49 +/- 0.58, ethanol 2.76 +/- 1.44, p < 0.001; GSH: control 10.13 +/- 4.45, ethanol 9.52 +/- 3.43, p < 0.05). In the pancreas, oxygen free radicals also led to membrane peroxidation (CD: control 3.70 +/- 1.67, ethanol 6.10 +/- 2.15, p < 0.05). When alcoholic pancreatitis was induced, the level of oxygen radicals further increased (GSSG: control 0.17 +/- 0.15, ethanol 0.27 +/- 0.17, p < 0.005, pancreatitis 0.42 +/- 0.29).
  
  
  CONCLUSIONS
  Ethanol induces the generation of oxygen radicals in pancreatic acinar cells. These levels increase upon induction of alcohol-induced pancreatitis. Similar to other models of acute pancreatitis, OFRs may therefore be involved in activating the cascade of self-digestion in alcohol-induced pancreatitis.
authors.affiliation: Department of General Surgery, University of Ulm, Ulm, Germany.
authors.forename: Uwe A
authors.initials: UA
authors.lastname: Wittel
authors.forename: Max
authors.initials: M
authors.lastname: Bachem
authors.forename: Marco
authors.initials: M
authors.lastname: Siech
mesh_terms: D000466:Alkadienes / Q000097:blood / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000494:pharmacology; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D019803:Glutathione Disulfide / Q000097:blood / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000466:Alkadienes; D017382:Reactive Oxygen Species; D000431:Ethanol; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione; D012844:Sincalide; D019803:Glutathione Disulfide