title: Reactive oxygen species by isoflurane mediates inhibition of nuclear factor κB activation in lipopolysaccharide-induced acute inflammation of the lung.
abstract: BACKGROUND
  Although anesthetic-induced inhibition of lipopolysaccharide (LPS)-induced lung injury has been recognized, the underlying mechanism is obscure. Some studies suggest that reactive oxygen species (ROS) by isoflurane play a crucial role for anesthetic-induced protective effects on the brain or the heart; however, it still remains controversial. In this study, we examined the role of isoflurane-derived ROS in isoflurane-induced inhibition of lung injury and nuclear factor κB (NFκB) activation in LPS-challenged rat lungs.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to inhalation of 1.0 minimum alveolar concentration of isoflurane for 60 minutes, and intratracheal LPS 0.1 mg was administered 60 minutes later. In some cases, ROS scavenger, 2-mercaptopropinyl glycine or N-acetylcysteine was given 30 minutes before isoflurane. ROS generation was measured by fluorometer before LPS challenge and 4 hours after. Isoflurane's preconditioning effect was assessed by histologic examination, protein content, neutrophil recruitment, and determination of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels in bronchoalveolar lavage fluid and lung tissue. Western blotting measured phosphorylation of inhibitory κB α (ser 32/36), NFκB p65, and inducible nitric oxide synthase (iNOS). TNF-α and IL-6 mRNA expression and immunofluorescence staining for iNOS were also assessed.
  
  
  RESULTS
  Isoflurane preconditioning reduced inflammatory lung injury and TNF-α, IL-1β, and IL-6 release in the lung. Isoflurane upregulated ROS generation before LPS but inhibited a ROS burst after LPS challenge. ROS scavenger administration before isoflurane abolished the isoflurane preconditioning effect as well as isoflurane-induced inhibition of phosphorylation of inhibitory κBα, NFκB p65, iNOS activation, and mRNA expression of TNF-α and IL-6 in acute LPS-challenged lungs.
  
  
  CONCLUSIONS
  This study suggests a crucial role of upregulated ROS generation by isoflurane for modification of inflammatory pathways by isoflurane preconditioning in acute inflammation of the lung.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: In Sun
authors.initials: IS
authors.lastname: Chung
authors.forename: Jie Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Ju A
authors.initials: JA
authors.lastname: Kim
authors.forename: Hyun Sung
authors.initials: HS
authors.lastname: Choi
authors.forename: Jeong Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Mikyung
authors.initials: M
authors.lastname: Yang
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015850:Interleukin-6 / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010641:Phenotype; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II