Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation

Abstract

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. Conclusion 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.