Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-3
pubmed:abstractText
Endotoxemia leads to the induction of inducible nitric oxide synthase (NOS-2) and increased expression of numerous inflammatory mediators contributing to endotoxin-induced acute lung injury. We tested the hypothesis that supplementation of nitric oxide (NO) by the novel NO donor S-nitroso human serum albumin (S-NO-HSA) given after lipopolysaccharide (LPS) challenge may reduce NOS-2 expression, lung inflammation and acute lung injury. Rats were divided into four groups: sham-operated (no treatment), LPS, LPS+HSA (human serum albumin), and LPS+S-NO-HSA. LPS was administered intravenously (20 mg kg(-1)) resulting in acute lung injury and a high mortality rate within 6 h (>90%). LPS-induced lung injury was characterized by an increased lung edema (lung wet/dry weight ratio), pulmonary neutrophil infiltration (myeloperoxidase activity, MPO) as well as a robust inflammatory response [increased expression of intercellular adhesion molecule-1 (ICAM-1), NOS-2, and cyclooxygenase-2 (COX-2)]. Infusion of S-NO-HSA or HSA was started 2 h after LPS and continued for 4 h (total dose of 72 mg kg(-1)) at a rate of 300 microg kg(-1) min(-1). S-NO-HSA but not HSA prolonged survival of endotoxemic rats, reduced the hypotensive response to LPS, minimized LPS-induced lung edema and injury, normalized MPO activity as well as diminished lung expression of pro-inflammatory molecules such as ICAM-1, NOS-2, and COX-2. Continuous supplementation of NO by S-NO-HSA after LPS challenge prevents induction of NOS-2, provides significant protection of endotoxin-induced acute lung injury, and prevents early mortality in endotoxic shock in rats. Our results suggest a potential therapeutic role for S-NO-HSA in endotoxemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1432-1912
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
379
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
281-90
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18854985-Animals, pubmed-meshheading:18854985-Blood Pressure, pubmed-meshheading:18854985-Cyclooxygenase 2, pubmed-meshheading:18854985-Disease Models, Animal, pubmed-meshheading:18854985-Drug Administration Schedule, pubmed-meshheading:18854985-Endotoxemia, pubmed-meshheading:18854985-Humans, pubmed-meshheading:18854985-Intercellular Adhesion Molecule-1, pubmed-meshheading:18854985-Kaplan-Meier Estimate, pubmed-meshheading:18854985-Lipopolysaccharides, pubmed-meshheading:18854985-Lung, pubmed-meshheading:18854985-Nitric Oxide Synthase Type II, pubmed-meshheading:18854985-Nitroso Compounds, pubmed-meshheading:18854985-Peroxidase, pubmed-meshheading:18854985-Pulmonary Edema, pubmed-meshheading:18854985-Rats, pubmed-meshheading:18854985-Rats, Wistar, pubmed-meshheading:18854985-Serum Albumin
pubmed:year
2009
pubmed:articleTitle
S-nitroso human serum albumin given after LPS challenge reduces acute lung injury and prolongs survival in a rat model of endotoxemia.
pubmed:affiliation
Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University Medical College, ul. Grzegórzecka 16, 31-531, Kraków, Poland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't