title: Sterile inflammation in hepatic ischemia/reperfusion injury: present concepts and potential therapeutics.
abstract: Ischemia and reperfusion (I/R) injury is an often unavoidable consequence of major liver surgery and is characterized by a sterile inflammatory response that jeopardizes the viability of the organ. The inflammatory response results from acute oxidative and nitrosative stress and consequent hepatocellular death during the early reperfusion phase, which causes the release of endogenous self-antigens known as damage-associated molecular patterns (DAMPs). DAMPs, in turn, are indirectly responsible for a second wave of reactive oxygen and nitrogen species (ROS and RNS) production by driving the chemoattraction of various leukocyte subsets that exacerbate oxidative liver damage during the later stages of reperfusion. In this review, the molecular mechanisms underlying hepatic I/R injury are outlined, with emphasis on the interplay between ROS/RNS, DAMPs, and the cell types that either produce ROS/RNS and DAMPs or respond to them. This theoretical background is subsequently used to explain why current interventions for hepatic I/R injury have not been very successful. Moreover, novel therapeutic modalities are addressed, including MitoSNO and nilotinib, and metalloporphyrins on the basis of the updated paradigm of hepatic I/R injury.
authors.affiliation: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.f.vangolen@amc.nl
authors.forename: Rowan F
authors.initials: RF
authors.lastname: van Golen
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Reiniers
authors.forename: Pim B
authors.initials: PB
authors.lastname: Olthof
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.forename: Michal
authors.initials: M
authors.lastname: Heger
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001324:Autoantigens / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D006498:Hepatectomy; D006801:Humans; D016031:Liver Transplantation; D018384:Oxidative Stress; D020011:Protective Agents / Q000627:therapeutic use; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control
chemical_list: D000893:Anti-Inflammatory Agents; D001324:Autoantigens; D015415:Biomarkers; D020011:Protective Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species