Linked Life Data

15328337

Source:http://linkedlifedata.com/resource/pubmed/id/15328337

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-11-4
pubmed:abstractText
The role of 5-lipoxygenase (5-LOX) in the pathophysiology of the organ injury/dysfunction caused by endotoxin is not known. Here, we investigate the effects of treatment with 5-LOX inhibitor zileuton in rats and targeted disruption of the 5-LOX gene in mice (5-LOX(-/-)) on multiple organ injury/dysfunction caused by severe endotoxemia. We also investigate the expression of beta2-integrins CD11a/CD18 and CD11b/CD18 on rat leukocytes by flow cytometry. Zileuton [3 mg/kg intravenously (i.v.)] or vehicle (10% dimethyl sulfoxide) was administered to rats 15 min prior to lipopolysaccharide (LPS; Escherichia coli, 6 mg/kg i.v.) or vehicle (saline). 5-LOX(-/-) mice and wild-type littermate controls were treated with LPS (E. coli, 20 mg/kg intraperitoneally) or vehicle (saline). Endotoxemia for 6 h in rats or 16 h in mice resulted in liver injury/dysfunction (increase in the serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin), renal dysfunction (creatinine), and pancreatic injury (lipase, amylase). Absence of functional 5-LOX (zileuton treatment or targeted disruption of the 5-LOX gene) reduced the multiple organ injury/dysfunction caused by endotoxemia. Polymorphonuclear leukocyte infiltration (myeloperoxidase activity) in the lung and ileum as well as pulmonary injury (histology) were markedly reduced in 5-LOX(-/-) mice. Zileuton also reduced the LPS-induced expression of CD11b/CD18 on rat leukocytes. We propose that endogenous 5-LOX metabolites enhance the degree of multiple organ injury/dysfunction caused by severe endotoxemia by promoting the expression of the adhesion molecule CD11b/CD18 and that inhibitors of 5-LOX may be useful in the therapy of the organ injury/dysfunction associated with endotoxic shock.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
961-70
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15328337-Animals, pubmed-meshheading:15328337-Antigens, CD11, pubmed-meshheading:15328337-Antigens, CD18, pubmed-meshheading:15328337-Arachidonate 5-Lipoxygenase, pubmed-meshheading:15328337-Chemotaxis, Leukocyte, pubmed-meshheading:15328337-Disease Models, Animal, pubmed-meshheading:15328337-Endotoxemia, pubmed-meshheading:15328337-Enzymes, pubmed-meshheading:15328337-Gene Targeting, pubmed-meshheading:15328337-Hydroxyurea, pubmed-meshheading:15328337-Leukocytes, pubmed-meshheading:15328337-Lipopolysaccharides, pubmed-meshheading:15328337-Lipoxygenase Inhibitors, pubmed-meshheading:15328337-Liver, pubmed-meshheading:15328337-Lung, pubmed-meshheading:15328337-Male, pubmed-meshheading:15328337-Mice, pubmed-meshheading:15328337-Mice, Knockout, pubmed-meshheading:15328337-Multiple Organ Failure, pubmed-meshheading:15328337-Pancreas, pubmed-meshheading:15328337-Rats, pubmed-meshheading:15328337-Rats, Wistar, pubmed-meshheading:15328337-Viscera
pubmed:year
2004
pubmed:articleTitle
Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton.
pubmed:affiliation
Centre for Experimental Medicine, Nephrology and Critical Care, The William Harvey Research Institute, Queen Mary, University of London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't