{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:01:24Z","timestamp":1789671684752,"version":"4.0.1"},"reference-count":163,"publisher":"Baishideng Publishing Group Inc.","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastrointest Surg"],"abstract":"<jats:p>Hepatic ischemia-reperfusion injury is a significant complication of liver surgery, including major hepatectomy, trauma surgery and liver transplantation. It is a key factor in postoperative organ failure, which negatively affects prognosis and overall patient survival. Beyond its localized hepatic effects, ischemia-reperfusion injury is increasingly recognized as a potent trigger of the systemic inflammatory response and remote organ damage. The cellular and molecular mechanisms involved are highly complicated and have yet to be entirely elucidated. The core pathophysiological mechanisms of hepatic ischemia-reperfusion injury include a transition to anaerobic metabolism and adenosine triphosphate depletion; the development of intracellular acidosis and calcium overload; the impairment of mitochondrial function; oxidative stress; the activation and accumulation of distinct cell populations, notably Kupffer cells, neutrophils and platelets; the upregulation and downregulation of microRNAs; increased nitric oxide production; and the triggering of an immune system response with the activation of the complement system and excessive cytokine release. Ischemic preconditioning (IP) is a surgical technique in which brief cycles of controlled ischemia followed by reperfusion are applied directly to an organ, aiming to enhance its tolerance to subsequent prolonged ischemia. Hepatic IP has been demonstrated to reduce ischemia-reperfusion injury by decreasing the release of proinflammatory cytokines and damage-associated molecular patterns; suppressing reactive oxygen species production; activating the antioxidant enzyme heme-oxygenase 1, caspase, heat shock proteins and protein kinase cascades; modulating energy supplies and electrolyte homeostasis; and intervening in cell death pathways. In addition to its local effects on the liver, growing evidence indicates that IP also provides systemic advantages by reducing the inflammatory response and limiting injury to distant organs following major hepatic injury. This review integrates current data on IP, highlighting its role in hepatic protection and prevention of remote organ damage, while exploring the underlying mechanisms and translational potential of this approach in hepatic surgery and transplantation.<\/jats:p>","DOI":"10.4240\/wjgs.v18.i2.114997","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T09:17:42Z","timestamp":1772011062000},"source":"Crossref","is-referenced-by-count":3,"title":["Protective effect of ischemic preconditioning against hepatic ischemia-reperfusion injury and associated remote organ damage"],"prefix":"10.4240","volume":"18","author":[{"given":"Christina","family":"Mouratidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios T","family":"Pavlidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Katsanos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafeim-Chrysovalantis","family":"Kotoulas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Kofinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra G","family":"Marneri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Massa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Tsoulfas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis N","family":"Galanis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros E","family":"Pavlidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2024.0222"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2016.00022"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112942"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2024.102416"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16219"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148815"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/lt.25189"},{"key":"B8","unstructured":"Eren EA, Latchana N, Beal E, Hayes D Jr, Whitson B, Black SM. Donations After Circulatory Death in Liver Transplant. Exp Clin Transplant 2016; 463-470"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.04.008"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2023.03.003"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00549-8"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/906965"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114299"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.626948"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.74.5.1124"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.24898"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.21037\/tgh-23-95"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-009-0878-7"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300622"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81422-1"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0308977"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i13.3572"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1113\/EP088394"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.09.019"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8910821"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7961"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/srep44356"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7555\/JBR.32.20180087"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.5812\/atr.12501"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60091507"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v9.i34.1261"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16396"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4240\/wjgs.v6.i7.122"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01566"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/s0925-4439(99)00114-3"},{"key":"B36","unstructured":"Li J, Li RJ, Lv GY, Liu HQ. The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci 2015; 2036-2047"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17702"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.04.036"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149630"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-009-8761-2"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23042357"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3727\/105221617X15042750874156"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8416763"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1159\/000485089"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.01.006"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103258"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i25.8082"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094642"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2020.03.014"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12091653"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6670579"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/cells12091273"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/goae066"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05588-8"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv137"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108719"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0173-8"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4110\/in.2018.18.e24"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24599"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/biom14010084"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.90"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq009"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.887565"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3390\/cells11142222"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.237"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1055\/s-0044-1786987"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2024.10.045"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.11.028"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2011.12.010"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s10353-015-0363-3"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.2174\/138161206777947597"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2016.05.050"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1399598"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25768"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300120"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2012.07187.x"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.9654"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21496"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v29.i33.4927"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10040791"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.2174\/2211536609666200129162531"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107604"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.10.182"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i14.2505"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-4274(02)00507-6"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v14.i3.504"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.84.3.253"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2014.06.024"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e32480"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.11864"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2015.04.049"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.756997"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.724471"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1159\/000072064"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i48.6058"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.14670\/HH-19.281"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3892\/br.2025.1927"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/620681"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2003.05.005"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i5.657"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/s1499-3872(14)60005-9"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i15.1871"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/s0168-8278(02)00327-6"},{"key":"B104","unstructured":"Zhang SJ, Zhu CJ, Zhao YF, Li J, Guo WZ. Different ischemic preconditioning for rat liver graft: protection and mechanism. Hepatobiliary Pancreat Dis Int 2003; 509-512"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2007.02.002"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20089"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.02009.x"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1590\/S0102-865020150070000002"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v9.i9.2025"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.20529"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.17179\/excli2017-166"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000175895.33415.cd"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199904270-00003"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1002\/lt.22204"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/s1091-255x(00)80031-1"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.2174\/138161206777947678"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431X20176185"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12398"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-012-0199-6"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050645"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-007-0004-7"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1038\/11072"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v5.i10.541"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.06.041"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.08.019"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.33134"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2009.0035"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-1426-1_6"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(02)01083-8"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2023.0492"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.314317"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117124"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2017.21.2.145"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199012000-00007"},{"key":"B135","unstructured":"Liu Q, Rehman H, Krishnasamy Y, Lemasters JJ, Zhong Z. Ischemic preconditioning attenuates acute lung injury after partial liver transplantation. Int J Physiol Pathophysiol Pharmacol 2018; 83-94"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1177\/15593258231169805"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14103530"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0744-z"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200204270-00004"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227038"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.07.008"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.08.020"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2012.01.077"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12582"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.713564"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00862.2016"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.124"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.05.004"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.5527\/wjn.v11.i1.13"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2012.27.5.547"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030539"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.12.025"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075950"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.12659\/AOT.938114"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1997.5217"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3468(98)90460-2"},{"key":"B157","unstructured":"Nikeghbalian S, Mansoorian MR, Hosseini SM, Mardani P, Geramizadeh B, Hosseini SA. Reduction of the severity of ischemia reperfusion-induced pancreatitis by ischemic pre-conditioning of the liver. Saudi J Kidney Dis Transpl 2009; 1010-1014"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.1013933"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2024.2361202"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.3892\/br.2013.153"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2019.90335"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1080\/08941939.2018.1556753"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000000243"}],"container-title":["World Journal of Gastrointestinal Surgery"],"original-title":[],"link":[{"URL":"https:\/\/www.wjgnet.com\/1948-9366\/full\/v18\/i2\/114997.htm","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.wjgnet.com\/1948-9366\/full\/v18\/i2\/114997.htm","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T09:18:20Z","timestamp":1772011100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.wjgnet.com\/1948-9366\/full\/v18\/i2\/114997.htm"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":163,"journal-issue":{"issue":"2"},"alternative-id":["114997"],"URL":"https:\/\/doi.org\/10.4240\/wjgs.v18.i2.114997","relation":{},"ISSN":["1948-9366"],"issn-type":[{"value":"1948-9366","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}