title: Delayed ischemic preconditioning protects against liver ischemia-reperfusion injury in vivo.
abstract: OBJECTIVE
  Ischemic preconditioning (IP) affords resistance to liver ischemia-reperfusion (IR) injury, providing an early phase of protection. Development of delayed IP against IR injury was assessed using partial IR in rat liver.
  
  
  METHODS
  The IP manuver (10 minutes of ischemia and up to 72 hours of reperfusion) was induced before 1 hour of ischemia and 20 hours of reperfusion. At the end of the reperfusion period, blood and liver samples were analyzed for serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), haptoglobin and tumor necrosis factor-alpha (TNF-alpha) levels, hepatic histology, protein carbonyl and glutathione (GSH) contents as well as nuclear factor-kappaB (NF-kappaB), and activating protein-1 (AP-1) DNA binding.
  
  
  RESULTS
  The IP manuver significantly increased protein carbonyl/GSH ratios (275%), serum ALT (42%), and AST (58%); these changes normalized after 12 hours. Serum AST, ALT, and LDH levels were significantly increased by IR (4-, 5.6-, and 7.0-fold, respectively), with significant changes in liver histology, protein carbonyl/GSH ratio (481% enhancement), and serum TNF-alpha (6.1-fold increase). Delayed IP in IR animals reduced serum AST (66%), ALT (57%), and LDH (90%) and liver GSH depletion (89%), with normalization of protein carbonyl content, serum TNF-alpha levels, and liver histology. Enhanced AP-1/NF-kappaB DNA binding ratios and diminished haptoglobin expression induced by IR were normalized by IP.
  
  
  CONCLUSIONS
  These data support that delayed IP suppresses IR-induced liver injury, oxidative stress, and TNF-alpha response, which coincide with recovery of IR-altered signaling functions represented by normal AP-1/NF-kappaB DNA binding ratios and acute phase responses.
authors.affiliation: Universidad de Chile, Facultad de Medicina, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Romanque
authors.forename: A
authors.initials: A
authors.lastname: Díaz
authors.forename: G
authors.initials: G
authors.lastname: Tapia
authors.forename: S
authors.initials: S
authors.lastname: Uribe-Echevarría
authors.forename: L A
authors.initials: LA
authors.lastname: Videla
authors.forename: V
authors.initials: V
authors.lastname: Fernandez
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006242:Haptoglobins / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control; D019194:Ischemic Preconditioning / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D006242:Haptoglobins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione