title: Alveolar oxidative stress is associated with elevated levels of nonenzymatic low-molecular-weight antioxidants in patients with different forms of chronic fibrosing interstitial lung diseases.
abstract: Increasing evidence indicates that disequilibrium of the alveolar oxidant-antioxidant balance may play a role in the pathogenesis of chronic fibrosing lung diseases. Excessive production of oxidants and a differential regulation of antioxidant enzymes have been described under these conditions. We characterized for the first time numerous nonenzymatic low-molecular-weight antioxidants in bronchoalveolar lavage fluids from patients with different forms of lung fibrosis initiated either by injury to the alveolar epithelium (idiopathic pulmonary fibrosis, IPF) or by inflammation (chronic sarcoidosis/hypersensitivity pneumonitis). Footprints of oxidative stress accompanied by an increase in the majority of antioxidants assessed were observed in all patient groups: elevated levels of uric acid, ascorbic acid, retinol, and alpha-tocopherol were noted, whereas glutathione levels were unchanged. The expression of Nrf2, an important redox-sensitive transcriptional regulator of antioxidants, was increased in IPF lungs. Our findings were corroborated in the bleomycin model of lung fibrosis where--aside from uric acid--nonenzymatic antioxidants were elevated during the fibrotic phase. In conclusion, alveolar levels of nonenzymatic antioxidants are elevated in fibrosing lung diseases, but are incapable of restoring oxidative balance. This increase may be part of an adaptive response to oxidative stress. However, a leakage from the blood may also contribute to our findings.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Markart
authors.forename: Thomas
authors.initials: T
authors.lastname: Luboeinski
authors.forename: Martina
authors.initials: M
authors.lastname: Korfei
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wygrecka
authors.forename: Poornima
authors.initials: P
authors.lastname: Mahavadi
authors.forename: Konstantin
authors.initials: K
authors.lastname: Mayer
authors.forename: Jochen
authors.initials: J
authors.lastname: Wilhelm
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Andreas
authors.initials: A
authors.lastname: Guenther
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000502:physiology; D001205:Ascorbic Acid / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D017563:Lung Diseases, Interstitial / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D011817:Rabbits; D014527:Uric Acid / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D000975:Antioxidants; D014801:Vitamin A; D014527:Uric Acid; D005978:Glutathione; D024502:alpha-Tocopherol; D001205:Ascorbic Acid