title: Propofol alleviates liver oxidative stress via activating Nrf2 pathway.
abstract: BACKGROUND
  Nuclear 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.
  
  
  METHODS
  Sprague-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.
  
  
  RESULTS
  Compared 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.
  
  
  CONCLUSIONS
  Protective effects of propofol against liver transplantation-induced graft-liver injury may be related with Keap1-Nrf2 signal pathway activation.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Ge
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: heiziqing@sina.com.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D018686:Anesthetics, Intravenous; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D015742:Propofol
keywords: Liver transplantation; Nuclear factor E2–related factor 2; Oxidative stress; Propofol