{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:50:57Z","timestamp":1791179457648,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3106,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>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\u00b0C 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 \u03bcM 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 (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.01). All treatment groups with IDN-6556 significantly increased bile production by 3-4-fold compared with controls (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.01), and reductions in alanine aminotransferase activities were seen within 90 minutes of reperfusion (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 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\u2013treated 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. <jats:italic toggle=\"yes\">Liver Transpl 13: 361\u2013366, 2007.<\/jats:italic> \u00a9 2007 AASLD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/lt.21016","type":"journal-article","created":{"date-parts":[[2007,2,22]],"date-time":"2007-02-22T23:03:29Z","timestamp":1172185409000},"page":"361-366","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":40,"title":["A Caspase Inhibitor, IDN-6556, Ameliorates Early Hepatic Injury in An Ex Vivo Rat Model of Warm and Cold Ischemia\u2020"],"prefix":"10.1097","volume":"13","author":[{"given":"Niel C.","family":"Hoglen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean M.","family":"Anselmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Katori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Kaldas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Da","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Valentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Lassman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald W.","family":"Busuttil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy W.","family":"Kupiec-Weglinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas G.","family":"Farmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-10-20250124","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1097\/00007890-198808000-00001","article-title":"Sinusoidal lining cell damage: the critical injury in cold preservation of liver allografts in the rat.","volume":"46","author":"McKeown","year":"1988","journal-title":"Transplantation"},{"key":"R2-10-20250124","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/00007890-199001000-00053","article-title":"Viability of sinusoidal lining cells in coldpreserved rat liver allografts.","volume":"49","author":"Holloway","year":"1990","journal-title":"Transplantation"},{"key":"R3-10-20250124","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1097\/00007890-198804000-00041","article-title":"Selective loss of nonparenchymal cell viability after cold ischemic storage of rat livers.","volume":"45","author":"CaldwellKenkel","year":"1988","journal-title":"Transplantation"},{"key":"R4-10-20250124","first-page":"83","article-title":"Kupffer cell activation and endothelial cell damage after storage of rat livers: effects of reperfusion.","volume":"13","author":"CaldwellKenkel","year":"1991","journal-title":"Hepatology"},{"key":"R5-10-20250124","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1146\/annurev.pharmtox.37.1.327","article-title":"Reperfusion injury after liver preservation for transplantation.","volume":"37","author":"Lemasters","year":"1997","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"R6-10-20250124","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1046\/j.1469-7580.2001.19850603.x","article-title":"Liver transplantation in man: morphometric analysis of the parenchymal alterations following cold ischaemia and warm ischaemiareperfusion.","volume":"198","author":"Vizzotto","year":"2001","journal-title":"J Anat"},{"key":"R7-10-20250124","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1600-0676.1994.tb00007.x","article-title":"Preservation of human liver grafts in UW solution. 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Modulating effects of FK506 and cyclosporine.","volume":"55","author":"Suzuki","year":"1993","journal-title":"Transplantation"},{"key":"R21-10-20250124","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1002\/hep.20157","article-title":"Sinusoidal endothelial cell and hepatocyte death following cold ischemiawarm reperfusion of the rat liver.","volume":"39","author":"Huet","year":"2004","journal-title":"Hepatology"},{"key":"R22-10-20250124","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/hep.20243","article-title":"Improvement of rat liver graft quality by pifithrin-mediated inhibition of hepatocyte necrapoptosis.","volume":"39","author":"ElGibaly","year":"2004","journal-title":"Hepatology"},{"key":"R23-10-20250124","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1053\/jlts.2002.32281","article-title":"Fate of hepatocyte and sinusoidal lining cell function and kinetics after extended cold preservation and transplantation of the rat liver.","volume":"8","author":"Miyagawa","year":"2002","journal-title":"Liver Transpl"},{"key":"R24-10-20250124","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/00007890-199907150-00025","article-title":"Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver.","volume":"68","author":"Sindram","year":"1999","journal-title":"Transplantation"},{"key":"R25-10-20250124","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1006\/mvre.2002.2404","article-title":"Prostaglandin E(1) protects human liver sinusoidal endothelial cells from apoptosis induced by hypoxia reoxygenation.","volume":"64","author":"Yang","year":"2002","journal-title":"Microvasc Res"},{"key":"R26-10-20250124","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/0022-4804(87)90033-3","article-title":"Bile flowan index of ischemic injury.","volume":"42","author":"Bowers","year":"1987","journal-title":"J Surg Res"},{"key":"R27-10-20250124","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0014-4800(03)00008-X","article-title":"Hepatic ischemiareperfusion injurya fresh look.","volume":"74","author":"Fondevila","year":"2003","journal-title":"Exp Mol Pathol"},{"key":"R28-10-20250124","doi-asserted-by":"crossref","first-page":"8915","DOI":"10.1073\/pnas.132026099","article-title":"Bucillamine, a thiol antioxidant, prevents transplantationassociated reperfusion injury.","volume":"99","author":"Amersi","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R29-10-20250124","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1097\/01.TP.0000141095.06273.10","article-title":"Caspase 3 inhibition improves survival and reduces early graft injury after ischemia and reperfusion in rat liver transplantation.","volume":"78","author":"Mueller","year":"2004","journal-title":"Transplantation"}],"container-title":["Liver Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flt.21016","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01445473-200703000-00010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T16:13:46Z","timestamp":1737735226000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01445473-200703000-00010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007]]}},"URL":"https:\/\/doi.org\/10.1002\/lt.21016","relation":{},"ISSN":["1527-6465"],"issn-type":[{"value":"1527-6465","type":"print"}],"subject":[],"published":{"date-parts":[[2007,3]]}}}