Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-8-12
pubmed:abstractText
The intravenous administration of lipopolysaccharide (LPS) to rats results in liver lesions characterized by the infiltration of both platelets and neutrophils into the liver and by midzonal hepatocellular necrosis. The liver injury is dependent on neutrophils, platelets and the coagulation system, as removal or inhibition of any of these components inhibits the development of hepatocellular necrosis. Platelet activating factor (PAF) and the cysteinyl leukotrienes (LTs) are potent inflammatory lipids that are critical for the development of some LPS-mediated alterations. To test the hypothesis that PAF, alone or in combination with LTs, contributes to the development of liver injury during LPS exposure, we conducted studies with the PAF receptor antagonist, WEB 2086, and the 5-lipoxygenase inhibitor, Zileuton. Female, Sprague-Dawley rats were pretreated with WEB 2086 (10 mg/kg, i.p.) alone or with Zileuton (40 mg/kg, p.o.) 1 h before the administration of LPS (4 mg/kg, i.v.) or its saline vehicle. Treatment with WEB 2086, alone or in combination with Zileuton, did not inhibit LPS-mediated hepatic neutrophil infiltration or liver injury, as assessed by histologic evaluation and increases in plasma alanine aminotransferase activity. Pretreatment with these agents also had no effect on the activation of the coagulation system or on the thrombocytopenia induced by LPS. These results suggest that PAF, alone or in combination with 5-lipoxygenase products, is not a critical mediator of LPS-induced hepatocellular injury in this model.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alanine Transaminase, http://linkedlifedata.com/resource/pubmed/chemical/Azepines, http://linkedlifedata.com/resource/pubmed/chemical/Fibrinogen, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyurea, http://linkedlifedata.com/resource/pubmed/chemical/Leukotrienes, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Platelet Activating Factor, http://linkedlifedata.com/resource/pubmed/chemical/Platelet Aggregation Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Triazoles, http://linkedlifedata.com/resource/pubmed/chemical/WEB 2086, http://linkedlifedata.com/resource/pubmed/chemical/zileuton
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9231696-Administration, Oral, pubmed-meshheading:9231696-Alanine Transaminase, pubmed-meshheading:9231696-Animals, pubmed-meshheading:9231696-Azepines, pubmed-meshheading:9231696-Blood Platelets, pubmed-meshheading:9231696-Drug-Induced Liver Injury, pubmed-meshheading:9231696-Female, pubmed-meshheading:9231696-Fibrinogen, pubmed-meshheading:9231696-Hydroxyurea, pubmed-meshheading:9231696-Injections, Intraperitoneal, pubmed-meshheading:9231696-Injections, Intravenous, pubmed-meshheading:9231696-Leukotrienes, pubmed-meshheading:9231696-Lipopolysaccharides, pubmed-meshheading:9231696-Lipoxygenase Inhibitors, pubmed-meshheading:9231696-Liver, pubmed-meshheading:9231696-Liver Diseases, pubmed-meshheading:9231696-Necrosis, pubmed-meshheading:9231696-Neutrophils, pubmed-meshheading:9231696-Platelet Activating Factor, pubmed-meshheading:9231696-Platelet Aggregation Inhibitors, pubmed-meshheading:9231696-Rats, pubmed-meshheading:9231696-Rats, Sprague-Dawley, pubmed-meshheading:9231696-Thrombocytopenia, pubmed-meshheading:9231696-Triazoles
pubmed:year
1997
pubmed:articleTitle
Neither platelet activating factor nor leukotrienes are critical mediators of liver injury after lipopolysaccharide administration.
pubmed:affiliation
Department of Pharmacology and Toxicology, Institute for Environmental Toxicology, Michigan State University, East Lansing 48824, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't