Hepatocellular oxidative stress and initial graft injury in human liver transplantation.
OBJECTIVE
The mechanisms underlying the initial graft dysfunction in liver transplantation are not completely understood, although much of the liver graft injury derives from the ischemia/reperfusion-induced oxidative stress. Thus, the purpose of our study was to determine the involvement of oxidative stress in the initial graft dysfunction in human liver transplantation.


METHODS
Liver biopsies were taken at different times of the transplantation procedure, at the organ donor laparatomy (T1), before graft reperfusion (T2), and 5-60 min after graft reperfusion (T3), determining the levels of GSH, GSSG, as well as peroxides and malondialdehyde in liver homogenates.


RESULTS
Patients were graded into two groups depending on whether the peak serum alanine aminotransferases within the first 3 postoperative days were lower (group A, mild to moderate injury: 32 patients) or higher (group B, severe injury: 5 patients) than 2500 U/l. The levels of GSH at time intervals T1-T3 were similar for groups A and B, with a trend to lower GSSG levels in group B at T2 and T3 samples. This outcome was accompanied by unchanged levels of malondialdehyde and hydrogen peroxide in the same samples in both groups of patients. No patient developed primary graft nonfunction. One-year cumulative survival was 81% and 60% in groups A and B, respectively (p>0.05).


CONCLUSIONS
These findings indicate a lack of significant generation of reactive oxygen species and consequent oxidative stress as a major factor involved in the pathogenesis of the initial graft dysfunction in human liver transplantation.
Ardite
E
E
Department of Medicine, Hospital Clinic, Universidad de Barcelona, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas, Spain.
Ramos
C
C
Rimola
A
A
Grande
L
L
Fernández-Checa
J C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006085:Graft Survival; D006498:Hepatectomy; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology* / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress; D015427:Reperfusion Injury; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting
D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D000410:Alanine Transaminase; D005978:Glutathione; D019803:Glutathione Disulfide