title: Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Stress.
abstract: BACKGROUND
  Oxidative stress is the predominant pathogenic mechanism of ischaemia-reperfusion (IR) injury. The noble gas argon has been shown to alleviate oxidative stress-related myocardial and cerebral injury. The risk of lung IR injury is increased in some major surgeries, reducing clinical outcome. However, no study has examined the lung-protective efficacy of argon preconditioning. The present study investigated the protective effects of argon preconditioning on airway epithelial cells exposed to hydrogen peroxide (H2O2) to induce oxidative stress.
  
  
  METHODS
  A549 airway epithelial cells were treated with a cytotoxic concentration of H2O2 after exposure to standard air or 30 or 50% argon/21% oxygen/5% carbon dioxide/rest nitrogen for 30, 45 or 180 min. Cells were stained with annexin V/propidium iodide, and apoptosis was evaluated by fluorescence-activated cell sorting. Protective signalling pathways activated by argon exposure were identified by Western blot analysis for phosphorylated candidate molecules of the mitogen-activated protein kinase and protein kinase B (Akt) pathways.
  
  
  RESULTS
  Preconditioning with 50% argon for 30, 45 and 180 min and 30% argon for 180 min caused significant protection of A549 cells against H2O2-induced apoptosis, with increases in cellular viability of 5-47% (p < 0.0001). A small adverse effect was also observed, which presented as a 12-15% increase in cellular necrosis in argon-treated groups. Argon exposure resulted in early activation of c-Jun N-terminal kinase (JNK) and p38, peaking 10- 30 min after the start of preconditioning, and delayed activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, peaking after 60-90 min.
  
  
  CONCLUSIONS
  Argon preconditioning protects airway epithelial cells from H2O2-induced apoptotic cell death. Argon activates the JNK, p38, and ERK1/2 pathways, but not the Akt pathway. The cytoprotective properties of argon suggest possible prophylactic applications in surgery-related IR injury of the lungs.
authors: Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors: Christina
authors: C
authors: Hafner
authors: Hong
authors: H
authors: Qi
authors: Lourdes
authors: L
authors: Soto-Gonzalez
authors: Katharina
authors: K
authors: Doerr
authors: Roman
authors: R
authors: Ullrich
authors: Eva Verena
authors: EV
authors: Tretter
authors: Klaus
authors: K
authors: Markstaller
authors: Klaus Ulrich
authors: KU
authors: Klein
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001128:Argon / Q000494:pharmacology*; D002478:Cells, Cultured; D019610:Cytoprotection; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D001128:Argon; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt