{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:41:05Z","timestamp":1790700065265,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T00:00:00Z","timestamp":1419206400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T00:00:00Z","timestamp":1419206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"The Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["21591748"],"award-info":[{"award-number":["21591748"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>Rho\u2010kinase (ROCK) inhibitors improve liver blood flow after ischemia\/reperfusion (IR) injury, especially in the setting of steatosis, by decreasing the resistance of intrahepatic microcirculation through hepatic stellate cell (HSC) relaxation. However, the systemic administration of ROCK inhibitors causes severe hypotension; therefore, liver\u2010specific ROCK inhibition is required. Here, we tested vitamin A (VA)\u2013coupled liposomes carrying the ROCK inhibitor Y\u201027632 for targeted HSCs in steatotic rats. Rat livers with steatosis induced by a choline\u2010deficient diet were subjected to IR injury. The delivery site and effect of the ROCK inhibitor were investigated. After liposomal Y\u201027632 injection, the survival rate after IR, the liver blood flow, the portal perfused pressure, and the hemodynamics were investigated. Immunohistochemical studies showed VA\u2013coupled liposome accumulation in livers. Liposomal Y\u201027632 was 100\u2010fold more effective in inhibiting HSC activation than free Y\u201027632. Liposomal Y\u201027632 improved the survival rate after IR injury, the liver blood flow, and the portal perfusion pressure without severe hypotension. In contrast, untargeted Y\u201027632 elicited severe systemic hypotension. We conclude that VA\u2013coupled liposomes carrying the ROCK inhibitor yield enhanced drug accumulation in the liver and thus mitigate IR injury in the steatotic liver and reduce major systemic adversity.<jats:italic toggle=\"yes\">Liver Transpl 21:123\u2010131, 2015<\/jats:italic>. \u00a9 2014 AASLD.<\/jats:p>","DOI":"10.1002\/lt.24020","type":"journal-article","created":{"date-parts":[[2014,10,11]],"date-time":"2014-10-11T05:28:57Z","timestamp":1413005337000},"page":"123-131","source":"Crossref","is-referenced-by-count":27,"title":["Rho\u2010kinase inhibitor targeting the liver prevents ischemia\/reperfusion injury in the steatotic liver without major systemic adversity in rats"],"prefix":"10.1097","volume":"21","author":[{"given":"Shintaro","family":"Kuroda","sequence":"first","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery,Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery,Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Services,Hiroshima University Hospital,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Services,Hiroshima University Hospital,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Tsutada","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Services,Hiroshima University Hospital,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Mikuriya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery,Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery,Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery,Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery,Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ohdan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery,Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2014,12,22]]},"reference":[{"key":"lt24020-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1097\/01.sla.0000251747.80025.b7","article-title":"Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case\u2010control study","volume":"245","year":"2007","journal-title":"Ann Surg"},{"key":"lt24020-bib-0002-20240115","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1002\/bjs.5820","article-title":"Steatosis predicts postoperative morbidity following hepatic resection for colorectal metastasis","volume":"94","year":"2007","journal-title":"Br J Surg"},{"key":"lt24020-bib-0003-20240115","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/S0168-8278(96)80195-4","article-title":"The use of donor fatty liver for liver transplantation: a challenge or a quagmire?","volume":"24","year":"1996","journal-title":"J Hepatol"},{"key":"lt24020-bib-0004-20240115","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/hep.1840200528","article-title":"Liver injury following normothermic ischemia in steatotic rat 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J Hepatol"},{"key":"lt24020-bib-0012-20240115","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1136\/gut.2007.144584","article-title":"Mechanisms of extrahepatic vasodilation in portal hypertension","volume":"57","year":"2008","journal-title":"Gut"},{"key":"lt24020-bib-0013-20240115","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1136\/gut.2005.081059","article-title":"Intrahepatic upregulation of RhoA and Rho\u2010kinase signalling contributes to increased hepatic vascular resistance in rats with secondary biliary cirrhosis","volume":"55","year":"2006","journal-title":"Gut"},{"key":"lt24020-bib-0014-20240115","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jhep.2011.04.029","article-title":"Rho inhibitor prevents ischemia\u2010reperfusion injury in rat steatotic liver","volume":"56","year":"2012","journal-title":"J 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