title: Reactive oxygen and nitrogen species in steatotic hepatocytes: a molecular perspective on the pathophysiology of ischemia-reperfusion injury in the fatty liver.
abstract: CONCLUSIONS
  Hepatic ischemia-reperfusion (IR) injury results from the temporary deprivation of hepatic blood supply and is a common side effect of major liver surgery (i.e., transplantation or resection). IR injury, which in most severe cases culminates in acute liver failure, is particularly pronounced in livers that are affected by non-alcoholic fatty liver disease (NAFLD). In NAFLD, fat-laden hepatocytes are damaged by chronic oxidative/nitrosative stress (ONS), a state that is acutely exacerbated during IR, leading to extensive parenchymal damage.
  
  
  BACKGROUND
  NAFLD triggers ONS via increased (extra)mitochondrial fatty acid oxidation and activation of the unfolded protein response. ONS is associated with widespread protein and lipid (per)oxidation, which reduces the hepatic antioxidative capacity and shifts the intracellular redox status toward an oxidized state. Moreover, activation of the transcription factor peroxisome proliferator-activated receptor α induces expression of mitochondrial uncoupling protein 2, resulting in depletion of cellular energy (ATP) reserves. The reduction in intracellular antioxidants and ATP in fatty livers consequently gives rise to severe ONS and necrotic cell death during IR.
  
  
  RESULTS
  Despite the fact that ONS mediates both NAFLD and IR injury, the interplay between the two conditions has never been described in detail. An integrative overview of the pathophysiology of NAFLD that renders steatotic hepatocytes more vulnerable to IR injury is therefore presented in the context of ONS.
  
  
  CONCLUSIONS
  Effective methods should be devised to alleviate ONS and the consequences thereof in NAFLD before surgery in order to improve resilience of fatty livers to IR injury.
authors.affiliation: Department of Surgery, Surgical Laboratory, Academic Medical Center, University of Amsterdam , Amsterdam, The Netherlands .
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Reiniers
authors.forename: Rowan F
authors.initials: RF
authors.lastname: van Golen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.forename: Michal
authors.initials: M
authors.lastname: Heger
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species