title: Increased glutathione levels contribute to the beneficial effects of hydrogen sulfide and inducible nitric oxide inhibition in allergic lung inflammation.
abstract: OBJECTIVE
  The interaction between nitric oxide (NO) and hydrogen sulfide (H2S) in the airways could have significant implications for the pathogenesis and therapeutic effects of both on lung diseases. In this study we investigated whether the beneficial effects of H2S on asthma could be comparable to that inhibition of inducible NO synthase (iNOS).
  
  
  METHODS
  Female BALB/C mice sensitized with ovalbumin (OVA) received either the H2S donor sodium hydrosulfide (NaHS, 14μmol/kg) or the iNOS inhibitor 1400W (1mg/kg), 30min before each OVA challenge during six days. On the first, second and sixth days, the leucocyte infiltration in lung parenchyma and bronchoalveolar lavage was evaluated. The aconitase activity (a sensor of O2 formation) and lipid peroxidation, as well as levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were determined in the lung tissues.
  
  
  RESULTS
  OVA-challenge caused a significant and time-dependent increase in the eosinophil number in the airways, which was accompanied by a significant decrease of aconitase activity and GSH/GSSG ratio along with enhanced lipid peroxidation in the lungs. Treatment with NaHS or 1400W significantly attenuated the airways eosinophilia that was paralleled by an increase in aconitase activity and decrease of lipid peroxidation. NaHS or 1400W treatments also reversed the decreased GSH/GSSG ratio seen after OVA-challenge.
  
  
  CONCLUSIONS
  The present study shows for the first time that the increased GSH/GSSG ratio caused by either H2S supplementation or iNOS-inhibition is a potential mechanism protecting airways against oxidative stress and inflammatory lung diseases.
authors.affiliation: Laboratory of Inflammation Research, São Leopoldo Mandic Institute and Research Center, Campinas, Sao Paulo, Brazil.
authors.forename: Daiana
authors.initials: D
authors.lastname: Campos
authors.affiliation: Laboratory of Bioenergetics, Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Felipe G
authors.initials: FG
authors.lastname: Ravagnani
authors.affiliation: Laboratory of Bioenergetics, Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Gurgueira
authors.affiliation: Laboratory of Bioenergetics, Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Teixeira
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.
authors.forename: Soraia K P
authors.initials: SKP
authors.lastname: Costa
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Muscará
authors.affiliation: Laboratory of Inflammation Research, São Leopoldo Mandic Institute and Research Center, Campinas, Sao Paulo, Brazil. Electronic address: heloisa.ferreira@slmandic.edu.br.
authors.forename: Heloisa H A
authors.initials: HHA
authors.lastname: Ferreira
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy*
chemical_list: D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000154:Aconitate Hydratase; D005978:Glutathione; D006862:Hydrogen Sulfide
keywords: 1400W; Aconitase; Ovalbumin; Oxidative stress; Reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio; Sodium hydrosulfide