title: Combined effects of a neutrophil elastase inhibitor (sivelestat sodium) and a free radical scavenger (edaravone) on lipopolysaccharide-induced acute lung injury in rats.
abstract: OBJECTIVE
  The present study aimed to investigate the combined effects of a neutrophil elastase inhibitor, sivelestat sodium, with a free radical scavenger, edaravone, on lipolysaccharide (LPS)-induced acute lung injury (ALI).
  
  
  METHODS
  Adult male Sprague-Dawley rats were anesthetized and instilled intratracheally with 2 mg/kg LPS. Sivelestat sodium (10 mg/kg, i.p.) and/or edaravone (8 mg/kg, i.p.) were administered 1 h after LPS instillation. The severity of pulmonary injuries was evaluated 12 h after inducing acute lung injury.
  
  
  RESULTS
  In lung tissues, either sivelestat or edaravone treatment alone showed significant protective effects against neutrophil infiltration and tissue injury, as demonstrated by myeloperoxidase activity and histopathological analysis. Sivelestat or edaravone treatment also attenuated the LPS-induced production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in rat lungs. However, the LPS-induced elevation of malondialdehyde levels in rat lungs was reduced only by edaravone, but not by sivelestat. In addition, combined treatment with both sivelestat and edaravone demonstrated additive protective effects on LPS-induced lung injury, compared with single treatments.
  
  
  CONCLUSIONS
  Combination of sivelestat and edaravone shows promise as a new treatment option for ALI/acute respiratory distress syndrome patients.
authors.affiliation: Department of Anesthesiology, Second Military Medical University, 800 Xiangyin Road, 200433, Shanghai, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.forename: Lulu
authors.initials: L
authors.lastname: Sun
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.forename: Jinbao
authors.initials: J
authors.lastname: Li
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Bao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
authors.forename: Jiong
authors.initials: J
authors.lastname: Hou
authors.forename: Yujian
authors.initials: Y
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004338:Drug Combinations; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D004338:Drug Combinations; D016166:Free Radical Scavengers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053491:Proteinase Inhibitory Proteins, Secretory; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; C069195:sivelestat; D009195:Peroxidase; D000077553:Edaravone; D000983:Antipyrine; D005998:Glycine