title: Remifentanil protects liver against ischemia/reperfusion injury through activation of anti-apoptotic pathways.
abstract: BACKGROUND
  Remifentanil protects against ischemia/reperfusion (I/R)-induced organ injury, although its underlying mechanism remains elusive. This study was designed to examine the protective effect of remifentanil preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanism involved.
  
  
  METHODS
  Adult Sprague-Dawley rats were randomly divided into sham operation (S group), ischemia/reperfusion (I/R group), and remifentanil preconditioning (R group) groups. Rats in the I/R group were subjected to a partial (70%) hepatic ischemia for 45 min, followed by 1 h, 3 h, and 6 h of reperfusion. Rats in the R group received venous injection of remifentanil (2 μg/kg/min) from 30 min prior to hepatic ischemia to the end of ischemia. Hepatic morphology and apoptosis were examined. Markers of liver damage, oxidative stress, and inflammation were evaluated. Mitochondrial function was assessed using mitochondrial membrane potential and appearance of mitochondrial swelling.
  
  
  RESULTS
  Compared with the S group, rats in the I/R group displayed a massive degenerative death in liver tissues and significantly enhanced cell apoptosis. Remifentanil preconditioning significantly reduced I/R-induced hepatocyte apoptosis. In addition, remifentanil protected against I/R-induced mitochondrial swelling and loss of membrane potential. Remifentanil preconditioning inhibited I/R-induced increases in tumor necrosis factor α, intercellular adhesion molecule 1, and nuclear factor κB p65 levels in liver tissues. Remifentanil preconditioning also inhibited the loss in superoxide dismutase and rise in malondialdehyde levels in liver tissues going through I/R injury.
  
  
  CONCLUSIONS
  Our data revealed that remifentanil preconditioning may turn on multiple cellular pathways in hepatocytes to protect the liver from I/R injury by alleviating hepatic apoptosis.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.forename: Haiyan
authors.initials: H
authors.lastname: Nan
authors.forename: Linfeng
authors.initials: L
authors.lastname: Yan
authors.forename: Haikang
authors.initials: H
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D010880:Piperidines; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000077208:Remifentanil
keywords: Apoptosis; Ischemia/reperfusion; Remifentanil