title: Liver glutathione depletion after preservation and reperfusion in human liver transplantation.
abstract: OBJECTIVE
  The oxidative stress is an important mechanism responsible for dysfunction after orthotopic liver transplantation (OLT). Glutathione (GSH) low levels after cold storage render the grafts vulnerable to reperfusion injury. Aim of this study was to evaluate GSH and oxidized glutathione (GSSG) liver concentrations, the hepatocellular injury and function in optimal and suboptimal grafts after human OLT.
  
  
  METHODS
  Liver biopsies were taken in 33 patients before the implant and two hours after reperfusion, allowing determination of GSH, GSSG and oxidative stress ratio (GSH/GSSG). Serum transaminases, prothrombin activity (PT) and factor V were measured to evaluate injury and function respectively. Histopathological injury was analyzed by an index of five parameters.
  
  
  RESULTS
  There was a decrease in GSH (p<0.01) after reperfusion (0.323 +/- 0.062 ìmol/g to 0.095 +/- 0.01 ìmol/g and 0.371 +/- 0.052 ìmol/g to 0.183 +/- 0.046 ìmol/g) in suboptimal and optimal groups, respectively. An increase of GSSG (p<0.05) occurred after reperfusion (0.172 +/- 0.038 ìmol/g to 0.278 +/- 0.077 ìmol/g and 0.229 +/- 0.048 ìmol/g to 0.356 +/- 0.105 ìmol/g) in suboptimal and optimal groups, respectively. A decrease (p<0.01) occurred in the GSH/GSSG ratio after reperfusion (2.23 +/- 0.31 to 0.482 +/- 0.042 and 2.47 +/- 0.32 to 0.593 +/- 0.068) in suboptimal and optimal groups, respectively. Histopathological injury scores were higher (p<0.05) in the suboptimal group than in optimal (6.46 +/- 0.4 vs. 5.39 +/- 1.1) and showed correlation with PT and factor V in the optimal group (p<0.05). Multivariate analysis pointed steatosis as an independent risk factor to histopathological injury (p<0.05).
  
  
  CONCLUSIONS
  There was a significant GSH depletion and GSSG formation after cold storage and reperfusion due to a similar oxidative stress in optimal and suboptimal grafts, but these levels were not related to graft viability.
authors.affiliation: Federal University of Rio Grande do Sul, and Hospital Dom Vicente Scherer, Rua Irmão José Otão 170/406, 90035-06 Porto Alegre, RS, Brazil. tomgrez@uol.com.br
authors.forename: Tomaz de Jesus Maria
authors.initials: Tde J
authors.lastname: Grezzana Filho
authors.forename: Carlos Otávio
authors.initials: CO
authors.lastname: Corso
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Zanotelli
authors.forename: Cláudio Augusto
authors.initials: CA
authors.lastname: Marroni
authors.forename: Ajácio Bandeira Mello
authors.initials: AB
authors.lastname: Brandão
authors.forename: Eduardo
authors.initials: E
authors.lastname: Schlindwein
authors.forename: Ian
authors.initials: I
authors.lastname: Leipnitz
authors.forename: Mário Henrique Mattos
authors.initials: MH
authors.lastname: Meine
authors.forename: Alfeu
authors.initials: A
authors.lastname: Fleck
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hoppen
authors.forename: Guillermo
authors.initials: G
authors.lastname: Kiss
authors.forename: Guido Pio Cracco
authors.initials: GP
authors.lastname: Cantisani
mesh_terms: D000328:Adult; D001706:Biopsy; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009926:Organ Preservation; D018384:Oxidative Stress / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018709:Statistics, Nonparametric
chemical_list: D005978:Glutathione; D019803:Glutathione Disulfide