Molecular mechanisms of alcoholic pancreatitis.
Alcoholic pancreatitis is a major complication of alcohol abuse. Since only a minority of alcoholics develop pancreatitis, there has been a keen interest in identifying the factors that may confer individual susceptibility to the disease. Numerous possibilities have been evaluated including diet, drinking patterns and a range of inherited factors. However, at the present time, no susceptibility factor has been unequivocally identified. In contrast, considerable progress has been made with respect to the constant effects of alcohol on the pancreas. The molecular mechanisms of alcohol-induced pancreatic injury are being increasingly defined with an emphasis, in recent years, on the acinar cell itself as the principal site on ethanol-related damage. It has now been established that the acinar cell is capable of metabolizing alcohol and that the direct toxic effects of alcohol and/or its metabolites on acinar cells may predispose the gland to autodigestive injury in the presence of an appropriate triggering factor. A significant recent development relates to the characterization of pancreatic stellate cells, increasingly implicated in alcoholic pancreatic fibrosis. Here the current concepts regarding the mechanisms/pathways mediating alcohol-induced pancreatic injury are outlined.
Apte
M V
MV
Pancreatic Research Group, University of New South Wales, Sydney, Australia. m.apte@unsw.edu.au
Pirola
R C
RC
Wilson
J S
JS
D000437:Alcoholism / Q000150:complications*; D000818:Animals; D001707:Biopsy, Needle; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008967:Molecular Biology; D018384:Oxidative Stress / Q000502:physiology*; D019512:Pancreatitis, Alcoholic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D051381:Rats; D012720:Severity of Illness Index
D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1