Oxygen radical production precedes alcohol-induced acute pancreatitis in rats.
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.
Wittel
Uwe A
UA
Department of General Surgery, University of Ulm, Ulm, Germany.
Bachem
Max
M
Siech
Marco
M
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
D000466:Alkadienes; D017382:Reactive Oxygen Species; D000431:Ethanol; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione; D012844:Sincalide; D019803:Glutathione Disulfide