N-acetylcysteine attenuates the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion in humans undergoing liver transplantation.
BACKGROUND
Oxidative stress and leukocyte-endothelial interactions contribute significantly to the reperfusion injury of the transplanted liver. Therefore, we investigated the effect of N-acetylcysteine (NAC) on reperfusion injury and circulating adhesion molecules during human liver transplantation.


METHODS
In a prospective study, 10 orthotopic liver transplantation patients were treated with high-dose NAC and 10 patients were treated with 5% glucose (placebo group) immediately before and during reperfusion of the donor liver. Parameters of hepatocellular injury, cellular oxygenation, plasma cytokines, and circulating adhesion molecules were determined at various time points during the liver transplantation.


RESULTS
NAC had no significant effect on the arterial lactate/pyruvate or hydroxybutyrate/acetoacetate ratio during the liver transplantation. At baseline, liver transplantation patients exhibited elevated levels of cytokines and circulating adhesion molecules compared with healthy volunteers (n=7). While no significant effect of NAC on circulating L- and P-selectin was observed, it significantly inhibited the increase in circulating ICAM-1 and VCAM-1 24 hr after reperfusion. There were no significant differences in maximal postoperative values of serum aspartate transaminase (peak AST) or alanine transaminase (peak ALT) between both groups. However, NAC significantly reduced the rise in alpha-glutathione S-transferase after reperfusion of the donor liver.


CONCLUSIONS
NAC attenuated the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion of the donor liver, indicating possible cytoprotective effects of NAC.
Weigand
M A
MA
Department of Anesthesiology, University of Heidelberg, Germany.
Plachky
J
J
Thies
J C
JC
Spies-Martin
D
D
Otto
G
G
Martin
E
E
Bardenheuer
H J
HJ
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D005260:Female; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005982:Glutathione Transferase; D000111:Acetylcysteine