Abstract
Background Liver transplantation leads to liver ischemia/reperfusion (I/R) injury, resulting in early graft dysfunction and failure. Exacerbations of oxidative stress and inflammatory response are key processes in the development of liver I/R injury. Intravenous anesthetic propofol potent effects on free radical scavenging and protects livers against I/R injury. However, the role and mechanism of propofol-mediated hepatic protection in liver transplantation is poorly understood. The aim of this study was to evaluate the role of propofol postconditioning in the liver I/R injury after liver transplantation. Methods Forty-eight rats were randomly divided into six groups: rats receiving either sham operation or orthotopic autologous liver transplantation (OALT) in the absence or presence of propofol (high dose and low dose) postconditioning or intralipid control or VAS2870 (Nox2 special inhibitor). Eight hours after OALT or sham operation, parameters of organ injury, oxidative stress, inflammation, and NADPH-associated proteins were assessed. Results After OALT, severe liver pathological injury was observed that was associated with increases of serum AST and ALT, which were attenuated by propofol postconditioning. In addition, especially high dose of propofol postconditioning reduced TNF-α, IL-1β, IL-6, TLR4, and NF-κB inflammatory pathway, accompanied with decrease of neutrophil elastase activity, MPO activity, 8-isoprotane, p47phox and gp91phox protein expressions, and increase of SOD activity. Inhibition of Nox2 by VAS2870 conferred similar protective effects in liver transplantation. Conclusion Liver transplantation leads to severe inflammation and oxidative stress with NADPH oxidase activation. Propofol postconditioning reduces liver I/R injury after liver transplantation partly via inhibiting NADPH oxidase Nox2 and the subsequent inflammation and oxidative stress.
Highlights
Liver transplantation has become the effective surgical treatment for patients with end-stage liver disease [1]
Na/K-ATPase neutrophil infiltration, were significantly elevated in rats subjected to orthotopic autologous liver transplantation (OALT). Both propofol postconditioning and VAS2870 treatment inhibited neutrophil infiltration caused by OALT and reduced lipid peroxidation product 8isoprostane generation and increased Superoxide dismutase (SOD) activity (Figures 5(c) and 5(d)) in the livers (P < 0 05 vs. OALT). These results indicated that propofol postconditioning and Nox2 inhibition protected the liver from oxidative stress via reduced neutrophil infiltration and reactive oxygen species (ROS) generation
Nox2 inhibition by VAS2870 reduced hepatocyte apoptosis compared to the OALT group. These results indicated that propofol postconditioning reduced hepatocyte ROS generation and protected hepatocyte from apoptosis
Summary
Liver transplantation has become the effective surgical treatment for patients with end-stage liver disease [1]. Liver ischemia reperfusion (I/R) injury is a severe postoperative complication during the early period after transplantation. It leads to early graft dysfunction and failure, which further results in acute and chronic rejection and irreversible death [2]. Liver transplantation leads to liver ischemia/reperfusion (I/R) injury, resulting in early graft dysfunction and failure. The aim of this study was to evaluate the role of propofol postconditioning in the liver I/R injury after liver transplantation. Liver transplantation leads to severe inflammation and oxidative stress with NADPH oxidase activation. Propofol postconditioning reduces liver I/R injury after liver transplantation partly via inhibiting NADPH oxidase Nox and the subsequent inflammation and oxidative stress
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