title: Propofol activation of the Nrf2 pathway is associated with amelioration of acute lung injury in a rat liver transplantation model.
abstract: OBJECTIVE
  This study aimed to investigate whether propofol pretreatment can protect against liver transplantation-induced acute lung injury (ALI) and to explore whether Nrf2 pathway is involved in the protections provided by propofol pretreatment.
  
  
  METHODS
  Adult male Sprague-Dawley rats were divided into five groups based on the random number table. Lung pathology was observed by optical microscopy. Lung water content was assessed by wet/dry ratio, and PaO2 was detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear Nrf2 was assayed by western blotting.
  
  
  RESULTS
  Compared with saline-treated model group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung injury caused by orthotopic autologous liver transplantation (OALT), decrease the lung injury scores, lung water content, and H2O2 and MDA levels, and improve the arterial PaO2 and SOD activity. Furthermore, propofol (but not N-acetylcysteine) pretreatment especially in high dose inhibited the expression of Keap1 and induced translocation of Nrf2 into the nucleus to further upregulate the expression of HO-1 and NQO1 downstream.
  
  
  CONCLUSIONS
  Pretreatment with propofol is associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved in the antioxidative processes.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450000, China.
authors.forename: Guosong
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Ailan
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D016031:Liver Transplantation / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014182:Transplantation, Autologous; D014867:Water / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D014867:Water; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D010100:Oxygen; D015742:Propofol