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

Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency. Free Radic Biol Med. 2017 Oct 02;: Authors: Dickerhof N, Pearson JF, Hoskin TS, Berry LJ, Turner R, Sly PD, Kettle AJ, AREST CF 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 0.2-6.92yr.). 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...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research