{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:10:18Z","timestamp":1792019418756,"version":"4.4.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3926,"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":[[2004,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Heme oxygenase (HO\u20131) provides a cellular defense mechanism during oxidative stress and catalyzes the rate\u2013limiting step in heme metabolism that produces biliverdin (BV). The role of BV and its potential use in preventing ischemia\/reperfusion injury (IRI) had never been studied. This study was designed to explore putative cytoprotective functions of BV during hepatic IRI in rat liver models of<\/jats:bold>\n                                 <jats:bold>\n                                    ex vivo\n                                 <\/jats:bold>\n                                 <jats:bold>perfusion and orthotopic liver transplantation (OLT) after prolonged periods of cold ischemia. In an<\/jats:bold>\n                                 <jats:bold>\n                                    ex vivo\n                                 <\/jats:bold>\n                                 <jats:bold>hepatic IRI model, adjunctive BV improved portal venous blood flow, increased bile production, and decreased hepatocellular damage. These findings were correlated with amelioration of histological features of IRI, as assessed by Suzuki's criteria. Following cold ischemia and syngeneic OLT, BV therapy extended animal survival from 50% in untreated controls to 90% to 100%. This effect correlated with improved liver function and preserved hepatic architecture. Additionally, BV adjuvant after OLT decreased endothelial expression of cellular adhesion molecules (P\u2013selectin and intracellular adhesion molecule 1), and decreased the extent of infiltration by neutrophils and inflammatory macrophages. BV also inhibited expression of inducible nitric oxide synthase and proinflammatory cytokines (interleukin 1\u03b2, tumor necrosis factor \u03b1, and interleukin 6) in OLTs. Finally, BV therapy promoted an increased expression of antiapoptotic molecules independently of HO\u20131 expression, consistent with BV being an important mediator through which HO\u20131 prevents cell death.<\/jats:bold>\n                                 <jats:bold>\n                                    In conclusion\n                                 <\/jats:bold>\n                                 <jats:bold>, this study documents and dissects potent cytoprotective effects of BV in well\u2013established rat models of hepatic IRI. Our results provide the rationale for a novel therapeutic approach using BV to maximize the function and thus the availability of donor organs. (Hepatology 2004;40:1333-1341.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20480","type":"journal-article","created":{"date-parts":[[2004,11,24]],"date-time":"2004-11-24T16:45:25Z","timestamp":1101314725000},"page":"1333-1341","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":137,"title":["Biliverdin Therapy Protects Rat Livers From Ischemia and Reperfusion Injury"],"prefix":"10.1097","volume":"40","author":[{"given":"Constantino","family":"Fondevila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2013Da","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Tsuchiyashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Csizmadia","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\u2013Weglinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz H.","family":"Bach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"issue":"Suppl 2","key":"R1-16-20241018","first-page":"1482","article-title":"Liver transplantation and rejection: an overview.","volume":"46","author":"Henderson","year":"1999","journal-title":"Hepatogastroenterology"},{"key":"R2-16-20241018","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1053\/jlts.2003.50105","article-title":"The utility of marginal donors in liver transplantation.","volume":"9","author":"Busuttil","year":"2003","journal-title":"Liver Transpl"},{"key":"R3-16-20241018","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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