Xanthine oxidase activity in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease

Pinamonti, S.; Muzzoli, Mariavittoria; Chicca, Milvia; Papi, Alberto; Ravenna, F; Fabbri, Leonardo M.; Ciaccia, A.

doi:10.1016/0891-5849(96)00030-5

Cited by 68 publications

(51 citation statements)

References 16 publications

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“…18 In our study, 8-isoprostane levels were higher in subjects with COPD than non-smokers, but levels were similar between subjects with COPD and smokers. This outcome might indicate that in smokers without any evidence of COPD, intensive pulmonary oxidative stress can develop similar to that seen in cases with COPD, suggestive of the presence of a damaged pulmonary parenchyma.…”

Section: Discussionsupporting

confidence: 40%

Oxidative Stress Levels in Exhaled Breath Condensate Associated With COPD and Smoking

Inonu¹,

Doruk²,

Sahin³

et al. 2012

Respir Care

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BACKGROUND: COPD is characterized by chronic air-flow limitation. Smoking is the most important factor in the pathogenesis of COPD. Smoking is associated with increased oxidative stress in the lungs. In this study our aim was to evaluate the differences in the burden of oxidative stress in patients with COPD, smokers, and non-smokers by measuring hydrogen peroxide (H 2 O 2 ), malondialdehyde (MDA), and 8-isoprostane levels in the exhaled breath condensate (EBC) samples. METHODS: Eighty subjects were included in the study. Group I (no. ‫؍‬ 25) had COPD, Group II (no. ‫؍‬ 26) was smokers, and Group III (no. ‫؍‬ 29) was nonsmokers. The severity of the COPD and dyspnea was assessed according to the results of pulmonary function tests (PFTs) and Medical Research Council (MRC) scale. RESULTS: The mean age of the subjects was 58 ؎ 8.9 years. While 8-isoprostane and H 2 O 2 levels were significantly higher in subjects with COPD (44.8 ؎ 40.2 pg/mL and 1.9 ؎ 0.8 mol/L) and smokers (41.3 ؎ 26 pg/mL and 1.7 ؎ 0.7 mol/L) than non-smokers (15.8 ؎ 6.9 pg/mL and 0.8 ؎ 0.4 mol/L), levels were similar between smokers and COPD subjects. MDA levels were similar between the 3 groups (P ‫؍‬ .31). There was no correlation between 8-isoprostane and H 2 O 2 levels and PFT parameters. There was a significant positive correlation between dyspnea grade on the MRC scale and 8-isoprostane levels (r ‫؍‬ 0.805, P < .001). CON-CLUSIONS: Even if respiratory function tests are within normal limits, oxidant burden in lungs of smokers is equivalent to that in COPD patients. 8-isoprostane could be useful in assessing symptom severity and health status of COPD patients.

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Section: Discussionsupporting

confidence: 40%

Oxidative Stress Levels in Exhaled Breath Condensate Associated With COPD and Smoking

Inonu¹,

Doruk²,

Sahin³

et al. 2012

Respir Care

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“…Interestingly, xanthine oxidase activity has been shown to be increased in cell-free BAL fluid and plasma from COPD patients, compared with normal subjects, and this has been associated with increased O 2 N-and lipid peroxide levels [32][33][34]. Cigarette smoking increases the formation of reactive nitrogen species (RNS) and results in nitration and oxidation of plasma proteins.…”

Section: Oxidative Stress In Bloodmentioning

confidence: 99%

Oxidative stress and redox regulation of lung inflammation in COPD

Rahman

Adcock²

2006

Eur Respir J

783

599

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Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (cJun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kBmediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kB-a kinase or the enhanced recruitment and activation of transcriptional coactivators. Enhanced NF-kB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression.Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity.The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/ quercetin and reserveratol), specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells.Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.

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“…More specifically, XOR is a source of superoxide and hydrogen peroxide within pulmonary EndoCs. Importantly, XOR protein and activity are elevated in human CS-induced lung disease (14,25). We have previously established that C57BL/6 mice exposed to CS have increased pulmonary XOR activity compared with filtered air-exposed controls (15 animals.…”

Section: Mif Is a Determinant Of Cs-induced Xor Activity And Ros Prodmentioning

confidence: 99%

“…XOR activity is elevated in patients with emphysema compared with control subjects (13,14), and XOR activity is increased in the lungs of animals exposed to CS (15). Importantly, XOR activity drives CS-induced DNA damage, specifically double-stranded DNA breaks, p53 expression, and EndoC apoptosis (15).…”

mentioning

confidence: 99%

Macrophage Migration Inhibitory Factor: A Novel Inhibitor of Apoptosis Signal-Regulating Kinase 1–p38–Xanthine Oxidoreductase–Dependent Cigarette Smoke–Induced Apoptosis

Fallica

Varela

Johnston

et al. 2016

Am J Respir Cell Mol Biol

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Cigarette smoke (CS) exposure is the leading cause of emphysema. CS mediates pathologic emphysematous remodeling of the lung via apoptosis of lung parenchymal cells resulting in enlargement of the airspaces, loss of the capillary bed, and diminished surface area for gas exchange. Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, is reduced both in a preclinical model of CS-induced emphysema and in patients with chronic obstructive pulmonary disease, particularly those with the most severe disease and emphysematous phenotype. MIF functions to antagonize CS-induced DNA damage, p53-dependent apoptosis of pulmonary endothelial cells (EndoCs) and resultant emphysematous tissue remodeling. Using primary alveolar EndoCs and a mouse model of CS-induced lung damage, we investigated the capacity and molecular mechanism(s) by which MIF modifies oxidant injury. Here, we demonstrate that both the activity of xanthine oxidoreductase (XOR), a superoxide-generating enzyme obligatory for CS-induced DNA damage and EndoC apoptosis, and superoxide concentrations are increased after CS exposure in the absence of MIF. Both XOR hyperactivation and apoptosis in the absence of MIF occurred via a p38 mitogen-activated protein kinase-dependent mechanism. Furthermore, a mitogen-activated protein kinase kinase kinase family member, apoptosis signal-regulating kinase 1 (ASK1), was necessary for CS-induced p38 activation and EndoC apoptosis. MIF was sufficient to directly suppress ASK1 enzymatic activity. Taken together, MIF suppresses CS-mediated cytotoxicity in the lung, in part by antagonizing ASK1-p38-XOR-dependent apoptosis.

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Xanthine oxidase activity in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease

Cited by 68 publications

References 16 publications

Oxidative Stress Levels in Exhaled Breath Condensate Associated With COPD and Smoking

Oxidative Stress Levels in Exhaled Breath Condensate Associated With COPD and Smoking

Oxidative stress and redox regulation of lung inflammation in COPD

Macrophage Migration Inhibitory Factor: A Novel Inhibitor of Apoptosis Signal-Regulating Kinase 1–p38–Xanthine Oxidoreductase–Dependent Cigarette Smoke–Induced Apoptosis

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