N-acetylcysteine attenuates the increase in alpha-glutathione, S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion in humans undergoingliver transplantation

Background. Oxidative stress and leukocyte-endothelial interactions contrib ute significantly to the reperfusion injury of the transplanted liver. Ther efore, we investigated the effect of N-acetyleysteine (NAC) on reperfusion injury and circulating adhesion molecules during human liver transplantatio n. Methods. In a prospective study, 10 orthotopic liver transplantation patien ts were treated with high-dose NAC and 10 patients were treated with 5% glu cose (placebo group) immediately before and during reperfusion of the donor liver. Parameters of hepatocellular injury, cellular oxygenation, plasma c ytokines, and circulating adhesion molecules were determined at various tim e 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 bas eline, liver transplantation patients exhibited elevated levels of cytokine s and circulating adhesion molecules compared with healthy volunteers (n=7) . While no significant effect of NAC on circulating L- and P-selectin was o bserved, it significantly inhibited the increase in circulating ICAM-1 and VCAM-1 24 hr after reperfusion. There were no significant differences in ma ximal postoperative values of serum aspartate transaminase (peak AST) or al anine transaminase (peak ALT) between both groups. However, NAC significant ly reduced the rise in alpha -glutathione S-transferase after reperfusion o f the donor liver. Conclusions. NAC attenuated the increase in alpha -glutathione S-transferas e and circulating ICAM-1 and VCAM-1 after reperfusion of the donor liver, i ndicating possible cytoprotective effects of NAC.