Source:http://linkedlifedata.com/resource/pubmed/id/17318854
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-3-5
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pubmed:abstractText |
This study examined the efficacy of the caspase inhibitor, IDN-6556, in a rat model of liver ischemia-reperfusion injury. Livers from male Sprague-Dawley rats were reperfused for 120 minutes after 24 hours of 4 degrees C cold storage in University of Wisconsin solution. Portal blood flow measurements estimated sinusoidal resistance, and bile production, alanine aminotransferase activities, and Suzuki scores were evaluated as parameters of hepatocyte/liver injury. Treated livers were exposed to 25 or 50 microM of IDN-6556 in University of Wisconsin storage solution and/or the perfusate. All treatment regimens with IDN-6556 significantly improved portal blood flow measured at 120 minutes, and significant improvements were seen as early as 30 minutes when inhibitor was also present in the perfusate (P < 0.01). All treatment groups with IDN-6556 significantly increased bile production by 3-4-fold compared with controls (P < 0.01), and reductions in alanine aminotransferase activities were seen within 90 minutes of reperfusion (P < 0.05). These data were confirmed by improved Suzuki scores (less sinusoidal congestion, necrosis, and vacuolization) in all treated groups. Livers from the IDN-6556-treated groups had markedly reduced caspase activities and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-positive cells, suggesting reductions in apoptosis. IDN-6556 present in cold storage media ameliorated liver injury due to cold ischemia and reperfusion injury and may be a rational therapeutic approach to reduce the risk of liver ischemia in the clinical setting.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(2-(2-tert-butylphenylaminooxalyl)...,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Organ Preservation Solutions,
http://linkedlifedata.com/resource/pubmed/chemical/Pentanoic Acids
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1527-6465
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pubmed:author |
pubmed-author:AnselmoDean MDM,
pubmed-author:BusuttilRonald WRW,
pubmed-author:FarmerDouglas GDG,
pubmed-author:HoglenNiel CNC,
pubmed-author:KaldasMarianM,
pubmed-author:KatoriMasamichiM,
pubmed-author:Kupiec-WeglinskiJerzy WJW,
pubmed-author:LassmanCharlesC,
pubmed-author:ShenXiu-DaXD,
pubmed-author:ValentinoKaren LKL
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pubmed:copyrightInfo |
(c) 2007 AASLD.
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
361-6
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pubmed:meshHeading |
pubmed-meshheading:17318854-Animals,
pubmed-meshheading:17318854-Apoptosis,
pubmed-meshheading:17318854-Caspases,
pubmed-meshheading:17318854-Enzyme Inhibitors,
pubmed-meshheading:17318854-Male,
pubmed-meshheading:17318854-Models, Animal,
pubmed-meshheading:17318854-Organ Preservation,
pubmed-meshheading:17318854-Organ Preservation Solutions,
pubmed-meshheading:17318854-Pentanoic Acids,
pubmed-meshheading:17318854-Rats,
pubmed-meshheading:17318854-Rats, Sprague-Dawley,
pubmed-meshheading:17318854-Reperfusion Injury,
pubmed-meshheading:17318854-Temperature,
pubmed-meshheading:17318854-Treatment Outcome
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pubmed:year |
2007
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pubmed:articleTitle |
A caspase inhibitor, IDN-6556, ameliorates early hepatic injury in an ex vivo rat model of warm and cold ischemia.
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pubmed:affiliation |
Idun Pharmaceuticals, San Diego, CA, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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