• J. Surg. Res. · Jun 2015

    Propofol alleviates liver oxidative stress via activating Nrf2 pathway.

    • Mian Ge, Weifeng Yao, Yanling Wang, Dongdong Yuan, Xinjin Chi, Gangjian Luo, and Ziqing Hei.
    • Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
    • J. Surg. Res. 2015 Jun 15;196(2):373-81.

    BackgroundNuclear factor-E2-related factor 2 (Nrf2)-mediated antioxidant response is the main protective system of graft-liver against ischemia-reperfusion injury after liver transplantation. Propofol is considered to confer protective effects on different organs; thus, we explored the possibility that whether propofol could attenuate graft-liver injury in a rat autologous orthotopic liver transplantation (AOLT) model and mechanisms were associated with activation of Nrf2 pathway.MethodsSprague-Dawley rats were randomly divided into four groups: sham-operated group, saline-treated AOLT group, low-dose propofol intervention group, and high-dose propofol intervention group. Liver injury was determined, and concentration of hydroxyl free radical (•OH), superoxide anion (O2(•-)), and malondialdehyde in the liver tissue were detected. The expression of Keap1, Nrf2, HO-1, and NQO1 were explored by Western blotting, and also the change of Nrf2 and keap1 was assessed by immunofluorescence.ResultsCompared with sham group, pathologic damage of graft-livers was in a time-dependent manner, accompanied with the increased level of oxidative stress in the AOLT group, and nuclear Nrf2 expression and its downstream antioxidant enzyme, HO-1 and NQO1, were also increased in this group. However, in propofol pretreatment groups especially in the high-dose group, the pathologic score was significantly decreased, accompanied with a lower level of •OH, O2(•-), and malondialdehyde than that of the AOLT group. The change of oxidative stress might be related to the Nrf2 pathway, evidenced as the elevation of protein expression level of NQO1, HO-1, and nuclear Nrf2.ConclusionsProtective effects of propofol against liver transplantation-induced graft-liver injury may be related with Keap1-Nrf2 signal pathway activation.Copyright © 2015 Elsevier Inc. All rights reserved.

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