title: Induction of heme oxygenase-1 by hemin protects lung against orthotopic autologous liver transplantation-induced acute lung injury in rats.
abstract: BACKGROUND
  Post-liver transplantation acute lung injury (ALI) severely affects patients' survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion-induced increased oxidative stress plays a critical role in mediating post-liver transplantation ALI and that induction of heme oxgenase-1 (HO-1), an enzyme with anti-oxidative stress properties, can confer effective protection of lung against ALI.
  
  
  METHODS
  Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (OALT) in the absence or presence of treatments with the selective HO-1 inducer (Hemin) or HO-1 inhibitor (ZnPP). Lung tissues were collected at 8 h after OALT, pathological scores and lung water content were evaluated; survival rate of rats was analyzed; protein expression of HO-1 was determined by western blotting, and nuclear translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor(NF)-κB p65 were detected by Immunofluorescence staining. The inflammatory cytokines and oxidative indexes of lung tissue were determined.
  
  
  RESULTS
  In lungs harvested at the early stage i.e. 8 h after OALT, Hemin treatment significantly increased superoxide dismutase activities, and reduced malondialdehyde, hydrogen peroxide, interleukin-6, myeloperoxidase, and tumor necrosis factor-α production,which were associated with increased HO-1 protein expression and lower pathological scores and increased survival rate of rats. The underline mechanisms might associate with activation of Nrf2 and inhibition of NF-κB p65 nuclear translocation. However, these changes were aggravated by ZnPP.
  
  
  CONCLUSIONS
  Hemin pretreatment, by enhancing HO-1 induction, increased lung antioxidant capacity and reduced inflammatory stress,protected the lung from OALT-induced ALI at early stage of reperfusion.
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China. chixinjin@yeah.net.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China. ann92929@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China. yaoweifeng881205@163.com.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Pathology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China. jinyibl@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China. wmrgwl@21cn.com.
authors.forename: Wanling
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China. cj_gz@tom.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China. heiziqing@sina.com.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D055371:Acute Lung Injury / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010100:Oxygen; D010313:Partial Pressure; D009195:Peroxidase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D016019:Survival Analysis; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D008315:Malondialdehyde; D006427:Hemin; D006861:Hydrogen Peroxide; D009195:Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D010100:Oxygen
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