{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:46:02Z","timestamp":1791135962374,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T00:00:00Z","timestamp":1072742400000},"content-version":"vor","delay-in-days":638,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["RO1 AI23847"],"award-info":[{"award-number":["RO1 AI23847"]}]},{"name":"NIH","award":["RO1 AI42223"],"award-info":[{"award-number":["RO1 AI42223"]}]},{"name":"BioStar University of California Grant; Sangstat Medical Corp."},{"name":"EC","award":["HO1 QLRT 2001-00422"],"award-info":[{"award-number":["HO1 QLRT 2001-00422"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>A direct role of carbon monoxide (CO), an effector-signaling molecule during heme oxygenase-1 (HO-1) catalysis of heme, in the protection against hepatic ischemia\/reperfusion (I\/R) injury needs to be established. This study was designed to determine the effects and downstream mechanisms of CO on cold I\/R injury in a clinically relevant isolated perfusion rat liver model. After 24 hours of cold storage, rat livers perfused <jats:italic toggle=\"yes\">ex vivo<\/jats:italic> for 2 hours with blood supplemented with CO (300 parts per million) showed significantly decreased portal venous resistance and increased bile production, as compared with control livers perfused with blood devoid of CO. These beneficial effects correlated with improved liver function (serum glutamic oxaloacetic transaminase levels) and diminished histological features of hepatocyte injury (Banff's scores). The CO-mediated cytoprotective effects were nitric oxide synthase- and cyclic guanine monophosphate-independent, but p38 mitogen-activated protein kinase (MAPK)-dependent. Moreover, adjunctive use of zinc protoporphyrin, a competitive HO-1 inhibitor, has shown that exogenous CO could fully substitute for endogenous HO-1 in preventing hepatic I\/R insult. This study performed in a clinically relevant <jats:italic toggle=\"yes\">ex vivo<\/jats:italic> cold ischemia model is the first to provide the evidence that HO-1-mediated cytoprotection against hepatic I\/R injury depends on the generation of, and can be substituted by, exogenous CO. The p38 MAPK signaling pathway represents the key downstream mechanism by which CO prevents the I\/R insult. In conclusion, regimens that employ exogenous CO should be revisited, as they may have potential applications in preventing\/mitigating I\/R injury, and thus expanding the liver donor pool for clinical transplantation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2002.32467","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T03:46:10Z","timestamp":1030247170000},"page":"815-823","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":204,"title":["Ex vivo exposure to carbon monoxide prevents hepatic ischemia\/reperfusion injury through p38 MAP kinase pathway"],"prefix":"10.1097","volume":"35","author":[{"given":"Farin","family":"Amersi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Da","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Anselmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Melinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhasani","family":"Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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