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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.
Antioxid Redox Signal. 2009 Feb; 11(2):227-40.AR

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+Show Affiliations

Department of Internal Medicine, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18783310

Citation

Markart, Philipp, et al. "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." Antioxidants & Redox Signaling, vol. 11, no. 2, 2009, pp. 227-40.
Markart P, Luboeinski T, Korfei M, et al. 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. Antioxid Redox Signal. 2009;11(2):227-40.
Markart, P., Luboeinski, T., Korfei, M., Schmidt, R., Wygrecka, M., Mahavadi, P., Mayer, K., Wilhelm, J., Seeger, W., Guenther, A., & Ruppert, C. (2009). 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. Antioxidants & Redox Signaling, 11(2), 227-40. https://doi.org/10.1089/ARS.2008.2105
Markart P, et al. 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. Antioxid Redox Signal. 2009;11(2):227-40. PubMed PMID: 18783310.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Markart,Philipp, AU - Luboeinski,Thomas, AU - Korfei,Martina, AU - Schmidt,Reinhold, AU - Wygrecka,Malgorzata, AU - Mahavadi,Poornima, AU - Mayer,Konstantin, AU - Wilhelm,Jochen, AU - Seeger,Werner, AU - Guenther,Andreas, AU - Ruppert,Clemens, PY - 2008/9/12/pubmed PY - 2009/4/21/medline PY - 2008/9/12/entrez SP - 227 EP - 40 JF - Antioxidants & redox signaling JO - Antioxid. Redox Signal. VL - 11 IS - 2 N2 - 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. SN - 1557-7716 UR - https://www.unboundmedicine.com/medline/citation/18783310/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_ L2 - https://www.liebertpub.com/doi/full/10.1089/ars.2008.2105?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -