title: Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models.
abstract: Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery. Understanding the mechanisms of liver ischemia reperfusion injury (IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation, as well as expanding the potential pool of usable donor grafts. The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes, increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis. Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury. IRI involves a complex interplay between neutrophils, natural killer T-cells cells, CD4+ T cell subtypes, cytokines, nitric oxide synthases, haem oxygenase-1, survival kinases such as the signal transducer and activator of transcription, Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways. Transgenic animals, particularly genetic knockout models, have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies. Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein. This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI.
authors.affiliation: Liver Transplantation and Hepatobiliary Unit, Division of Surgery and Interventional Science, Royal Free Campus, University College London, Royal Free Hampstead NHS Trust Hospital, London NW 2QG, United Kingdom. gourab.datta@yahoo.co.uk
authors.forename: Gourab
authors.initials: G
authors.lastname: Datta
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Fuller
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D008099:Liver / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008102:Liver Circulation; D008107:Liver Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation; D011379:Prognosis; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015415:Biomarkers
keywords: Haem oxygenase; Ischemia/reperfusion; Knockout; Liver; Mitogen-activated protein kinase; Nitric oxide synthase; T cell receptor; Transgenic
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