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
Autor: | Werner Seeger, Clemens Ruppert, Malgorzata Wygrecka, Konstantin Mayer, Philipp Markart, T Luboeinski, Reinhold Schmidt, Jochen Wilhelm, Andreas Guenther, Martina Korfei, Poornima Mahavadi |
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Rok vydání: | 2009 |
Předmět: |
Physiology
Pulmonary Fibrosis Blotting Western alpha-Tocopherol Clinical Biochemistry Low molecular weight antioxidants Ascorbic Acid medicine.disease_cause Biochemistry Antioxidants Pathogenesis medicine Animals Humans In patient Vitamin A Molecular Biology General Environmental Science Inflammation Lung business.industry Cell Biology respiratory system Glutathione Immunohistochemistry Idiopathic Pulmonary Fibrosis Uric Acid Oxidative Stress medicine.anatomical_structure Immunology General Earth and Planetary Sciences Rabbits Lung Diseases Interstitial business Bronchoalveolar Lavage Fluid Oxidative stress |
Zdroj: | Antioxidants & Redox Signaling. 11:227-240 |
ISSN: | 1557-7716 1523-0864 |
Popis: | 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. |
Databáze: | OpenAIRE |
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