Source:http://linkedlifedata.com/resource/pubmed/id/19915515
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2010-2-15
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pubmed:abstractText |
Ischemia-reperfusion injury (IRI) is a leading cause of acute tubular necrosis (ATN) and delayed graft function in transplanted organs. Up-regulation of matrix metalloproteinases (MMPs) propagates the microinflammatory response that drives IRI. This study sought to determine the specific effects of Marimastat (Vernalis, BB-2516), a broad spectrum MMP and TNF-alpha-converting enzyme inhibitor, on IRI-induced ATN. Mice were pretreated with Marimastat or methylcellulose vehicle for 4 d before surgery. Renal pedicles were bilaterally occluded for 30 min and allowed to reperfuse for 24 h. Baseline creatinine levels were consistent between experimental groups; however, post-IRI creatinine levels were 4-fold higher in control mice (p < 0.0001). The mean difference between the post-IRI histology grades of Marimastat-treated and control kidneys was 1.57 (p = 0.003), demonstrating more severe damage to control kidneys. Post-IRI mean (+/-SEM) MMP-2 activity rose from baseline levels in control mice (3.62 +/- 0.99); however, pretreated mice presented only a slight increase in mean MMP-2 activity (1.57 +/- 0.72) (p < 0.001). In conclusion, these data demonstrate that MMP inhibition is associated with a reduction of IRI in a murine model.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Creatinine,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Mmp2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mmp9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/marimastat
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1530-0447
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
257-62
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pubmed:meshHeading |
pubmed-meshheading:19915515-Animals,
pubmed-meshheading:19915515-Biological Markers,
pubmed-meshheading:19915515-Blotting, Western,
pubmed-meshheading:19915515-Creatinine,
pubmed-meshheading:19915515-Disease Models, Animal,
pubmed-meshheading:19915515-Hydroxamic Acids,
pubmed-meshheading:19915515-Kidney,
pubmed-meshheading:19915515-Kidney Tubular Necrosis, Acute,
pubmed-meshheading:19915515-Male,
pubmed-meshheading:19915515-Matrix Metalloproteinase 2,
pubmed-meshheading:19915515-Matrix Metalloproteinase 9,
pubmed-meshheading:19915515-Mice,
pubmed-meshheading:19915515-Mice, Inbred C57BL,
pubmed-meshheading:19915515-Protease Inhibitors,
pubmed-meshheading:19915515-Reperfusion Injury,
pubmed-meshheading:19915515-Severity of Illness Index
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pubmed:year |
2010
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pubmed:articleTitle |
Effects of metalloproteinase inhibition in a murine model of renal ischemia-reperfusion injury.
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pubmed:affiliation |
Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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