title: Ethanol induced acinar cell injury.
abstract: Ethanol abuse is a well known association of pancreatitis. Research into the pathogenesis of alcoholic pancreatitis has generally followed two directions. Firstly, factors which may predispose alcoholics to pancreatitis have been examined. To date, these studies have been negative and the predisposing factor(s) remain unknown. The second approach has involved studies on the constant metabolic effects of ethanol on the pancreas which may render the acinar cell susceptible to digestive enzyme induced injury. Recently developed models of experimental pancreatitis have implicated intracellular activation of digestive enzymes by lysosomal enzymes as an early event. Using the Lieber-DeCarli model of ethanol administration to rats, a number of changes have been described in pancreatic acinar cells which may predispose the gland to autodigestion. These changes include: (1) increased glandular content of digestive enzymes as a result of increases in mRNA levels for these enzymes; (2) increased glandular content of the lysosomal enzyme cathepsin B (known to be capable of activating trypsinogen); (3) increased fragility of lysosomes possibly mediated by cholesteryl esters and fatty acid ethyl esters; and (4) increased fragility of zymogen granules. These effects of ethanol constitute a "primed" setting (the "Drinker's Pancreas") for autodigestion. Triggering factors for autodigestion in this setting have not yet been identified.
authors.affiliation: Department of Gastroenterology, Prince of Wales Hospital, Sydney, Australia.
authors.forename: M V
authors.initials: MV
authors.lastname: Apte
authors.forename: I D
authors.initials: ID
authors.lastname: Norton
authors.forename: J S
authors.initials: JS
authors.lastname: Wilson
mesh_terms: D000818:Animals; D004792:Enzyme Precursors / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008247:Lysosomes / Q000187:drug effects; D008954:Models, Biological; D010179:Pancreas / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D019512:Pancreatitis, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D004792:Enzyme Precursors; D000431:Ethanol