Liver glutathione depletion after preservation and reperfusion in human liver transplantation.
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.
Grezzana Filho
Tomaz de Jesus Maria
Tde J
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
Corso
Carlos Otávio
CO
Zanotelli
Maria Lúcia
ML
Marroni
Cláudio Augusto
CA
Brandão
Ajácio Bandeira Mello
AB
Schlindwein
Eduardo
E
Leipnitz
Ian
I
Meine
Mário Henrique Mattos
MH
Fleck
Alfeu
A
Hoppen
Ricardo
R
Kiss
Guillermo
G
Cantisani
Guido Pio Cracco
GP
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
D005978:Glutathione; D019803:Glutathione Disulfide