title: Oxidation contributes to low glutathione in the airways of children with cystic fibrosis.
abstract: Glutathione is an important antioxidant in the lungs but its concentration is low in the airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress contributes to lowering glutathione is unknown. We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass spectrometry and immunological techniques. The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis, whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage. The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age. Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset and progression of lung disease in cystic fibrosis.
authors.affiliation: Centre for Free Radical Research, Dept of Pathology, University of Otago Christchurch, Christchurch, New Zealand tony.kettle@otago.ac.nz.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kettle
authors.affiliation: Centre for Free Radical Research, Dept of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Rufus
authors.initials: R
authors.lastname: Turner
authors.affiliation: Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Australia.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gangell
authors.affiliation: Centre for Free Radical Research, Dept of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Harwood
authors.affiliation: Centre for Free Radical Research, Dept of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Irada S
authors.initials: IS
authors.lastname: Khalilova
authors.affiliation: Centre for Free Radical Research, Dept of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Chapman
authors.affiliation: Centre for Free Radical Research, Dept of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Winterbourn
authors.affiliation: Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry; D007249:Inflammation; D008168:Lung / Q000378:metabolism; D013058:Mass Spectrometry; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry*; D009195:Peroxidase / Q000737:chemistry; D013902:Radiography, Thoracic; D012137:Respiratory System / Q000378:metabolism; D012189:Retrospective Studies; D013450:Sulfones / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D000975:Antioxidants; D013450:Sulfones; C430906:glutathione sulfonamide; D006997:Hypochlorous Acid; D009195:Peroxidase; D005978:Glutathione; D010100:Oxygen