Linked Life Data

15976389

Source:http://linkedlifedata.com/resource/pubmed/id/15976389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-12
pubmed:abstractText
Chronic alcohol consumption is known to increase the susceptibility to acute and chronic pancreatitis, and it is likely that a cofactor is required to initiate the progression to alcoholic pancreatitis. The severity and complications of alcoholic and nonalcoholic acute pancreatitis may be influenced by a number of cofactors, including endotoxemia. To explore the effect of a possible cofactor, we used endotoxin [lipopolysaccharide (LPS)] as a tool to induce cellular injury in the alcoholic pancreas. Single, increasing doses of endotoxin were injected in rats fed an alcohol or control diet and killed 24 h after the injection. We examined the mechanism by which LPS exacerbates pancreatic injury in alcohol-fed rats and whether the injury is associated with apoptosis or necrosis. We showed that chronic alcohol exposure alone inhibits apoptosis through the intrinsic pathway and the downstream apoptosis executor caspase-3 compared with the controls. Pancreatic necrosis and inflammation increased after LPS injection in control and alcohol-fed rats in a dose-dependent fashion but with a significantly greater response in the alcohol-fed animals. Caspase activities and TdT-mediated dUTP nick-end labeling positivity were lower in the alcoholic pancreas injected with LPS, whereas the histopathology and inflammation were more severe compared with the control-fed animals. Assessment of a putative indicator of necrosis, the ratio of ADP to ATP, indicated that alcohol exposure accelerates pancreatic necrosis in response to endotoxin. These findings suggest that the pancreas exposed to alcohol is more sensitive to LPS-induced damage because of increased sensitivity to necrotic cell death rather than apoptotic cell death. Similar to the liver, the pancreas is capable of responding to LPS with a more severe response in alcohol-fed animals, favoring pancreatic necrosis rather than apoptosis. We speculate that this mechanism may occur in acute alcoholic pancreatitis patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G232-41
pubmed:dateRevised
2010-2-8
pubmed:meshHeading
pubmed-meshheading:15976389-Adenosine Triphosphate, pubmed-meshheading:15976389-Animals, pubmed-meshheading:15976389-Antigens, Neoplasm, pubmed-meshheading:15976389-Apoptosis, pubmed-meshheading:15976389-Caspases, pubmed-meshheading:15976389-Central Nervous System Depressants, pubmed-meshheading:15976389-Endotoxins, pubmed-meshheading:15976389-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:15976389-Ethanol, pubmed-meshheading:15976389-Heme Oxygenase-1, pubmed-meshheading:15976389-Immunohistochemistry, pubmed-meshheading:15976389-In Situ Nick-End Labeling, pubmed-meshheading:15976389-Lectins, C-Type, pubmed-meshheading:15976389-Lithostathine, pubmed-meshheading:15976389-Male, pubmed-meshheading:15976389-Necrosis, pubmed-meshheading:15976389-Pancreas, pubmed-meshheading:15976389-Rats, pubmed-meshheading:15976389-Rats, Sprague-Dawley, pubmed-meshheading:15976389-Tumor Markers, Biological
pubmed:year
2006
pubmed:articleTitle
Pancreatic response to endotoxin after chronic alcohol exposure: switch from apoptosis to necrosis?
pubmed:affiliation
University Hospital Zurich, Department of Visceral and Transplantation Surgery, Sternwartstrasse 14, CH-8091 Zurich, Switzerland. franco.fortunato@usz.ch
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural