title: Role of alcohol metabolism in chronic pancreatitis.
abstract: Alcohol abuse is the major cause of chronic inflammation of the pancreas (i.e., chronic pancreatitis). Although it has long been thought that alcoholic pancreatitis is a chronic disease from the outset, evidence is accumulating to indicate that chronic damage in the pancreas may result from repeated attacks of acute tissue inflammation and death (i.e., necroinflammation). Initially, research into the pathogenesis of alcoholic pancreatitis was related to ductular and sphincteric abnormalities. In recent years, the focus has shifted to the type of pancreas cell that produces digestive juices (i.e., acinar cell). Alcohol now is known to exert a number of toxic effects on acinar cells. Notably, acinar cells have been shown to metabolize alcohol (i.e., ethanol) via both oxidative (i.e., involving oxygen) and nonoxidative pathways. The isolation and study of pancreatic stellate cells (PSCs)-the key effectors in the development of connective tissue fibers (i.e., fibrogenesis) in the pancreas-has greatly enhanced our understanding of the pathogenesis of chronic pancreatitis. Pancreatic stellate cells become activated in response to ethanol and acetaldehyde, a toxic byproduct of alcohol metabolism. In addition, PSCs have the capacity to metabolize alcohol via alcohol dehydrogenase (the major oxidizing enzyme for ethanol). The fact that only a small percentage of heavy alcoholics develop chronic pancreatitis has led to the search for precipitating factors of the disease. Several studies have investigated whether variations in ethanol-metabolizing enzymes may be a trigger factor for chronic pancreatitis, but no definite relationship has been established so far.
authors: South Western Sydney Clinical School, University of New South Wales, Sydney, Australia.
authors: Alain
authors: A
authors: Vonlaufen
authors: Jeremy S
authors: JS
authors: Wilson
authors: Romano C
authors: RC
authors: Pirola
authors: Minoti V
authors: MV
authors: Apte
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000437:Alcoholism / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity; D014644:Genetic Variation; D006801:Humans; D010179:Pancreas / Q000187:drug effects; D019512:Pancreatitis, Alcoholic / Q000235:genetics / Q000503:physiopathology*
chemical_list: D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase
references: Gastroenterology. 2000 Apr;118(4):780-94
references: 10734030
references: Intern Med. 2001 May;40(5):368-75
references: 11393404
references: Gastroenterology. 2002 Jan;122(1):106-18
references: 11781286
references: J Gastroenterol Hepatol. 2002 Feb;17(2):177-82
references: 11966948
references: Am J Physiol Gastrointest Liver Physiol. 2002 Jul;283(1):G65-73
references: 12065293
references: Pancreas. 2003 Nov;27(4):311-5
references: 14576493
references: Pancreas. 2003 Nov;27(4):316-20
references: 14576494
references: Alcohol Alcohol. 2004 Jan-Feb;39(1):20-4
references: 14691069
references: Gastroenterology. 2003 Dec;125(6):1845-59
references: 14724836
references: Pancreatology. 2004;4(2):82-9
references: 15056978
references: Am J Gastroenterol. 2004 Nov;99(11):2256-70
references: 15555009
references: Pancreas. 2005 May;30(4):e87-91
references: 15841033
references: Gut. 2006 Jan;55(1):79-89
references: 16043492
references: Gastroenterology. 2006 Mar;130(3):781-93
references: 16530519
references: Pancreas. 2006 May;32(4):351-9
references: 16670617
references: Ann Surg. 1991 Dec;214(6):671-8
references: 1720611
references: Gastroenterology. 1990 Jan;98(1):191-6
references: 2293577
references: Am J Physiol. 1986 May;250(5 Pt 1):G598-606
references: 2422952
references: Addict Biol. 1998 Apr;3(2):137-50
references: 26734819
references: Gut. 1994 Apr;35(4):552-6
references: 8174996
references: J Lab Clin Med. 1993 Jun;121(6):759-64
references: 8505587
references: Hepatology. 1997 Jan;25(1):112-7
references: 8985275
references: Biochim Biophys Acta. 1997 Jul 19;1336(1):89-98
references: 9271254
references: Gut. 1998 Jul;43(1):128-33
references: 9771417
references: J Lab Clin Med. 1998 Oct;132(4):294-302
references: 9794700