Source:http://linkedlifedata.com/resource/pubmed/id/16226725
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2005-10-31
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| pubmed:abstractText |
Ethyl pyruvate (EP) is a simple aliphatic ester derived from the endogenous metabolite, pyruvic acid. EP has been shown to decrease the expression of various pro-inflammatory mediators, including nitric oxide (NO*), tumor necrosis factor (TNF), cyclooxygenase-2, and interleukin (IL)-6, in a variety of in vitro and in vivo model systems. In an effort to better understand the chemical features that might explain the anti-inflammatory properties of EP, we screened 15 commercially available compounds for cytoprotective or anti-inflammatory effects using two in vitro assay systems: TNF and NO* production by lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage-like cells and changes in the permeability of Caco-2 human enterocyte-like monolayers stimulated with a cocktail of pro-inflammatory cytokines called cytomix (1000U/ml IFN-gamma plus 10ng/ml TNF-alpha plus 1ng/ml IL-1beta). Two compounds, namely diethyl oxaloproprionate (DEOP) and 2-acetamidoacrylate (2AA), demonstrated consistent anti-inflammatory or cytoprotective pharmacological properties in this screening process. Treatment of mice with either of these compounds ameliorated LPS-induced ileal mucosal hyperpermeability to the fluorescent probe, fluorescein isothiocyanate-labeled dextran (average molecular mass 4kDa), and bacterial translocation to mesenteric lymph nodes. Treatment with either of these compounds also improved survival in mice challenged with a lethal dose of LPS. Finally, in a study that compared 2AA to its methyl ester, we showed that methyl-2-acetamidoacrylate is at least 100-fold more potent than the parent carboxylate as an inhibitor of LPS-induced NO* production by RAW 264.7 cells. Collectively, these data are consistent with the view that anti-inflammatory activity is demonstrable for a number of compounds that either incorporate an olefinic linkage conjugated to a carbonyl moiety or are capable of undergoing tautomeric rearrangement to form such a structure. Moreover, our findings suggest that esters with these general characteristics, perhaps because of their greater lipophilicity or electrophilicity, are more potent anti-inflammatory agents than are the parent carboxylates.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acrylates,
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/N-acetyldehydroalanine,
http://linkedlifedata.com/resource/pubmed/chemical/N-acetyldehydroalanine methyl ester,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Propionates,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0006-2952
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| pubmed:author |
pubmed-author:AjamiAlfred AAA,
pubmed-author:CruzRuy JRJJr,
pubmed-author:DeludeRussell LRL,
pubmed-author:EnglertJoshua AJA,
pubmed-author:FinkMitchell PMP,
pubmed-author:HanYushengY,
pubmed-author:HaradaTomoyukiT,
pubmed-author:KilleenMeaghan EME,
pubmed-author:SappingtonPenny LPL,
pubmed-author:YangRunkuanR
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| pubmed:issnType |
Print
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| pubmed:day |
25
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| pubmed:volume |
70
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1579-92
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16226725-Acrylates,
pubmed-meshheading:16226725-Alanine,
pubmed-meshheading:16226725-Animals,
pubmed-meshheading:16226725-Anti-Inflammatory Agents,
pubmed-meshheading:16226725-Cell Line,
pubmed-meshheading:16226725-Drug Evaluation, Preclinical,
pubmed-meshheading:16226725-Esters,
pubmed-meshheading:16226725-Glutathione,
pubmed-meshheading:16226725-Humans,
pubmed-meshheading:16226725-Inflammation,
pubmed-meshheading:16226725-Lipid Peroxidation,
pubmed-meshheading:16226725-Lipopolysaccharides,
pubmed-meshheading:16226725-Male,
pubmed-meshheading:16226725-Mice,
pubmed-meshheading:16226725-Mice, Inbred C57BL,
pubmed-meshheading:16226725-Molecular Structure,
pubmed-meshheading:16226725-NF-kappa B,
pubmed-meshheading:16226725-Nitric Oxide,
pubmed-meshheading:16226725-Propionates,
pubmed-meshheading:16226725-Tumor Necrosis Factor-alpha
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| pubmed:year |
2005
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| pubmed:articleTitle |
The ethyl pyruvate analogues, diethyl oxaloproprionate, 2-acetamidoacrylate, and methyl-2-acetamidoacrylate, exhibit anti-inflammatory properties in vivo and/or in vitro.
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| pubmed:affiliation |
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 616 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
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| pubmed:publicationType |
Journal Article
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