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      Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency.

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          Abstract

          Neutrophil-derived myeloperoxidase (MPO) is recognized as a major source of oxidative stress at the airway surface of a cystic fibrosis (CF) lung where, despite limited evidence, the antioxidant glutathione is widely considered to be low. The aims of this study were to establish whether oxidative stress or glutathione status are associated with bronchiectasis and whether glutathione deficiency is inherently linked to CF or a consequence of oxidative stress. MPO was measured by ELISA in 577 bronchoalveolar lavage samples from 205 clinically-phenotyped infants and children with CF and 58 children without CF (ages 0.2-6.92 years). Reduced glutathione (GSH), oxidized glutathione species (GSSG; glutathione attached to proteins, GSSP; glutathione sulfonamide, GSA) and allantoin, an oxidation product of uric acid, were measured by mass spectrometry. The odds of having bronchiectasis were associated with MPO and GSSP. GSH was low in children with CF irrespective of oxidation. Oxidized glutathione species were significantly elevated in CF children with pulmonary infections compared to uninfected CF children. In non-CF children, infections had no effect on glutathione levels. An inadequate antioxidant response to neutrophil-mediated oxidative stress during infections exists in CF due to an inherent glutathione deficiency. Effective delivery of glutathione and inhibition of MPO may slow the development of bronchiectasis.

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          Author and article information

          Journal
          Free Radic. Biol. Med.
          Free radical biology & medicine
          Elsevier BV
          1873-4596
          0891-5849
          December 2017
          : 113
          Affiliations
          [1 ] Centre for Free Radical Research, Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand. Electronic address: nina.dickerhof@otago.ac.nz.
          [2 ] Biostatistics and Computational Biology Unit, University of Otago Christchurch, Christchurch, New Zealand.
          [3 ] Centre for Free Radical Research, Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
          [4 ] Telethon Kids Institute, West Perth, Western Australia, Australia.
          [5 ] Child Health Research Centre, University of Queensland, Brisbane, Australia.
          Article
          S0891-5849(17)30781-5
          10.1016/j.freeradbiomed.2017.09.028
          28982600
          fa63ff93-c1f1-4832-a530-6f624fe7d204
          History

          Oxidative stress,Protein S-glutathionylation,Glutathione,Myeloperoxidase,Neutrophil,Neutrophil elastase

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