{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:37:43Z","timestamp":1790213863412,"version":"4.1.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Novartis\/Canadian Liver Foundation Hepatology Research Chair at the Universit\u00e9 de Montr\u00e9al"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Liver ischemia\/reperfusion injury (IRI) is an important cause of liver damage especially early after liver transplantation, following liver resection, and in other clinical situations. Using rat experimental models, we identified oxaloacetate (OAA) as a key metabolite able to protect hepatocytes from hypoxia and IRI. In vitro screening of metabolic intermediates beneficial for hepatocyte survival under hypoxia was performed by measures of cell death and injury. In vivo, the effect of OAA was evaluated using the left portal vein ligation (LPVL) model of liver ischemia and a model of warm IRI. Liver injury was evaluated in vivo by serum transaminase levels, liver histology, and liver weight (edema). Levels and activity of caspase 3 were also measured. In vitro, the addition of OAA to hepatocytes kept in a hypoxic environment significantly improved cell viability (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01), decreased cell injury (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01), and improved energy metabolism (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01). Administration of OAA significantly reduced the extent of liver injury in the LPVL model with lower levels of alanine aminotransferase (ALT; <jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01), aspartate aminotransferase (AST; <jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01), and reduced liver necrosis (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.05). When tested in a warm IRI model, OAA significantly decreased ALT (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.001) and AST levels (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.001), prevented liver edema (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.001), significantly decreased caspase 3 expression (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01), as well as histological signs of cellular vesiculation and vacuolation (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.05). This was associated with higher adenosine triphosphate (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.05) and energy charge levels (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.01). In conclusion, OAA can significantly improve survival of ischemic hepatocytes. The hepatoprotective effect of OAA was associated with increased levels of liver bioenergetics both in vitro and in vivo. These results suggest that it is possible to support mitochondrial activity despite the presence of ischemia and that OAA can effectively reduce ischemia\u2010induced injury in the liver.<\/jats:p>","DOI":"10.1002\/lt.25415","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T08:44:05Z","timestamp":1548060245000},"page":"627-639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Oxaloacetate Protects Rat Liver From Experimental Warm Ischemia\/Reperfusion Injury by Improving Cellular Energy Metabolism"],"prefix":"10.1097","volume":"25","author":[{"given":"Gr\u00e9gory","family":"Merlen","sequence":"first","affiliation":[{"name":"Laboratoire d\u2019H\u00e9patologie Cellulaire,Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Universit\u00e9 de Montr\u00e9al,Montreal,Quebec,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie\u2010Ann","family":"Raymond","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9patologie Cellulaire,Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Universit\u00e9 de Montr\u00e9al,Montreal,Quebec,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamir","family":"Cassim","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9patologie Cellulaire,Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Universit\u00e9 de Montr\u00e9al,Montreal,Quebec,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Lapierre","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9patologie Cellulaire,Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Universit\u00e9 de Montr\u00e9al,Montreal,Quebec,Canada"},{"name":"D\u00e9partement de M\u00e9decine,Universit\u00e9 de Montr\u00e9al,Montreal,Quebec,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bilodeau","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9patologie Cellulaire,Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Universit\u00e9 de Montr\u00e9al,Montreal,Quebec,Canada"},{"name":"D\u00e9partement de M\u00e9decine,Universit\u00e9 de Montr\u00e9al,Montreal,Quebec,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"lt25415-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1097\/01.TP.0000062574.18648.7C","article-title":"Liver transplantation from controlled non\u2010heart\u2010beating donors: an increased incidence of biliary 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