title: Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved.
abstract: OBJECTIVE
  Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism.
  
  
  METHODS
  We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors.
  
  
  RESULTS
  The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells.
  
  
  CONCLUSIONS
  This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia-induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway.
authors.affiliation: a 1 Department of Respiratory Diseases, ChangHai Hospital , Second Military Medical University , Shanghai, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Cao
authors.affiliation: b 2 Department of Respiratory Diseases, Jing'an District Centre Hospital of Shanghai , Huashan Hospital Fudan University, Jing'An Branch , Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.affiliation: a 1 Department of Respiratory Diseases, ChangHai Hospital , Second Military Medical University , Shanghai, China.
authors.forename: Yunye
authors.initials: Y
authors.lastname: Ning
authors.affiliation: b 2 Department of Respiratory Diseases, Jing'an District Centre Hospital of Shanghai , Huashan Hospital Fudan University, Jing'An Branch , Shanghai, China.
authors.forename: Zinan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: b 2 Department of Respiratory Diseases, Jing'an District Centre Hospital of Shanghai , Huashan Hospital Fudan University, Jing'An Branch , Shanghai, China.
authors.forename: Weihao
authors.initials: W
authors.lastname: Li
authors.affiliation: a 1 Department of Respiratory Diseases, ChangHai Hospital , Second Military Medical University , Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000077553:Edaravone; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D018496:Hyperoxia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077553:Edaravone; D000983:Antipyrine
keywords: HO-1; PI3K/Akt pathway; edaravone; hyperoxia; oxidative injury