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. 2014 Jul;44(1):122-9.
doi: 10.1183/09031936.00170213. Epub 2014 Mar 23.

Oxidation contributes to low glutathione in the airways of children with cystic fibrosis

Anthony J Kettle  1 , Rufus Turner  2 , Catherine L Gangell  3 , D Timothy Harwood  2 , Irada S Khalilova  2 , Anna L Chapman  2 , Christine C Winterbourn  2 , Peter D Sly  3 ; AREST CF
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Free article

Oxidation contributes to low glutathione in the airways of children with cystic fibrosis

Anthony J Kettle et al. Eur Respir J. 2014 Jul.
Free article

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.

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