Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation.
BACKGROUND
The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation.


METHODS
Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days.


RESULTS
There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT.


CONCLUSIONS
Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation.
Grezzana
T J M
TJ
Liver Transplantation Group, Irmandade Santa Casa de Misericórdia de Porto Alegre, Brazil. tomgrez@terra.com.br
Corso
C O
CO
Zanotelli
M L
ML
Marroni
C A
CA
Brandão
A B M
AB
Schlindwein
E
E
Leipnitz
I
I
Meine
M H M
MH
Fleck
A
A
Cassal
A
A
Hope
L
L
Hoppen
R
R
Kiss
G
G
Gleisner
A L M
AL
Cerski
T
T
Bellò-Klein
A
A
Severo
V
V
Innocenti
C
C
Cantisani
G P C
GP
D000241:Adenosine; D000328:Adult; D000493:Allopurinol; D002423:Cause of Death; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007328:Insulin; D008099:Liver; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000401:mortality / Q000502:physiology*; D008297:Male; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions; D018384:Oxidative Stress / Q000502:physiology*; D011887:Raffinose; D015427:Reperfusion Injury; D012189:Retrospective Studies
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D019803:Glutathione Disulfide