Intravenous Anesthetic Protects Hepatocyte from Reactive Oxygen Species‐Induced Cellular Apoptosis during Liver Transplantation In Vivo

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.

The inhibition of apoptosis through myocardial postconditioning by affecting Fas/FasIg signaling through miR139‐3p and miR181a‐1

“…26 Propofol PostC, however, has been demonstrated to reduce hepatic I/R injury by inhibiting Nox following liver transplantation. 27 The present study showed that PostC decreased Cybb expression in cases of I/R injury.…”

“…It was shown that Nox proteins contributed to the action mechanisms of preconditioning (PreC) and that Cybb was required for the activation of the protective effect of PreC in myocardial I/R models 26 . Propofol PostC, however, has been demonstrated to reduce hepatic I/R injury by inhibiting Nox following liver transplantation 27 . The present study showed that PostC decreased Cybb expression in cases of I/R injury.…”

Aerosol inhalation of a hydrogen-rich solution restored septic renal function

“…Kidney tissues (100 mg) were homogenized, and a bicinchoninic acid protein assay was used to quantify the protein levels. A heparin binding protein primary antibody (1:1000, Abcam, USA) was used for Western blotting, which was performed as described in our previous study [39].…”

Dexmedetomidine Alleviates Hypoxia‐Induced Synaptic Loss and Cognitive Impairment via Inhibition of Microglial NOX2 Activation in the Hippocampus of Neonatal Rats

“…There is a close interdependence between oxidative stress and neuroinflammation. Increases in intracellular ROS are known to promote NF- κ B activation, which subsequently regulates the transcription of proinflammatory cytokines and other mediators involved in acute inflammation [ 47 , 48 ]. Dexmedetomidine has been reported to prevent NF- κ B translocation into the nucleus and thus reduce the production of proinflammatory cytokines, thus exerting a protective effect against brain damage [ 49 , 50 ].…”