Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-11-16
pubmed:abstractText
Previously we reported that alcohol abuse increases the incidence of the acute respiratory distress syndrome (ARDS) in septic patients, and that chronic ethanol ingestion in rats depletes alveolar epithelial glutathione and increases endotoxin-mediated lung edema. In this study we examined a potential mechanism by which ethanol-induced glutathione depletion could predispose to acute lung injury. We hypothesized that glutathione depletion activates matrix metalloproteinases (MMPs), thereby increasing degradation of the alveolar extracellular matrix (ECM) during sepsis. Ethanol-fed rats (20% vol/vol in water for 6 wk) were given endotoxin (2 mg/kg, intraperitoneally) followed 2 h later by lung isolation and ex vivo perfusion with n-formyl-methionyl-leucyl-phenylalanine (fMLP) (10(-)(7) M). Ethanol ingestion increased (p < 0.05) MMP-9 and MMP-2 activity, as determined by zymography, in the lung tissue and lavage fluid compared with control-fed rats, and increased (p < 0.05) levels of the 7S fragment of type IV collagen in the lung lavage fluid. Ethanol ingestion increased activation, but not production, of the MMP-9 and MMP-2 zymogens. Finally, although concomitant ingestion of N-acetylcysteine had no effect (p > 0.05) on MMP production, it increased (p > 0.05) lung glutathione levels, blocked (p < 0.05) MMP-9 and MMP-2 activation, and decreased (p < 0.05) levels of the 7S fragment of type IV collagen. We conclude that chronic ethanol ingestion, via glutathione depletion, activates MMPs during sepsis, thereby increasing degradation of the alveolar epithelial ECM. Lois M, Brown LAS, Moss IM, Roman J, Guidot DM. Ethanol ingestion increases activation of matrix metalloproteinases in rat lungs during acute endotoxemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1073-449X
pubmed:author
pubmed:issnType
Print
pubmed:volume
160
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1354-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10508828-Acetylcysteine, pubmed-meshheading:10508828-Acute Disease, pubmed-meshheading:10508828-Animals, pubmed-meshheading:10508828-Bronchoalveolar Lavage Fluid, pubmed-meshheading:10508828-Collagen, pubmed-meshheading:10508828-Endotoxemia, pubmed-meshheading:10508828-Endotoxins, pubmed-meshheading:10508828-Enzyme Activation, pubmed-meshheading:10508828-Ethanol, pubmed-meshheading:10508828-Glutathione, pubmed-meshheading:10508828-Glutathione Disulfide, pubmed-meshheading:10508828-Lung, pubmed-meshheading:10508828-Male, pubmed-meshheading:10508828-Matrix Metalloproteinase 2, pubmed-meshheading:10508828-Matrix Metalloproteinase 9, pubmed-meshheading:10508828-Matrix Metalloproteinases, pubmed-meshheading:10508828-Proteins, pubmed-meshheading:10508828-Rats, pubmed-meshheading:10508828-Rats, Sprague-Dawley, pubmed-meshheading:10508828-Salmonella typhimurium
pubmed:year
1999
pubmed:articleTitle
Ethanol ingestion increases activation of matrix metalloproteinases in rat lungs during acute endotoxemia.
pubmed:affiliation
Division of Pulmonary Medicine, Atlanta Veterans Affairs Medical Center, Georgia, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't