Oxidative stress in stable cystic fibrosis patients: Do we need higher antioxidant plasma levels?

Lezo, Antonela; Biasi, Fiorella; Massarenti, Paola; Calabrese, R.; Poli, Giuseppe; Santini, B; Bignamini, Elisabetta

doi:10.1016/j.jcf.2012.06.002

Cited by 27 publications

(23 citation statements)

References 27 publications

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“…5B). This agrees with the conventional paradigm in CF that ROS production by immune cells represents the major cause of airway injury, together with deficient anti-oxidant and anti-protease defences [31], [32].…”

Section: Resultssupporting

confidence: 90%

Reactive-Oxygen-Species-Mediated P. aeruginosa Killing Is Functional in Human Cystic Fibrosis Macrophages

Cifani¹,

Pompili²,

Anile

et al. 2013

PLoS ONE

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Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in cystic fibrosis (CF) patients. About 80% of adult CF patients have chronic P. aeruginosa infection, which accounts for much of the morbidity and most of the mortality. Both bacterial genetic adaptations and defective innate immune responses contribute to the bacteria persistence. It is well accepted that CF transmembrane conductance regulator (CFTR) dysfunction impairs the airways-epithelium-mediated lung defence; however, other innate immune cells also appear to be affected, such as neutrophils and macrophages, which thus contribute to this infectious pathology in the CF lung. In macrophages, the absence of CFTR has been linked to defective P. aeruginosa killing, increased pro-inflammatory cytokine secretion, and reduced reactive oxygen species (ROS) production. To learn more about macrophage dysfunction in CF patients, we investigated the generation of the oxidative burst and its impact on bacterial killing in CF macrophages isolated from peripheral blood or lung parenchyma of CF patients, after P. aeruginosa infection. Our data demonstrate that CF macrophages show an oxidative response of similar intensity to that of non-CF macrophages. Intracellular ROS are recognized as one of the earliest microbicidal mechanisms against engulfed pathogens that are activated by macrophages. Accordingly, NADPH inhibition resulted in a significant increase in the intracellular bacteria survival in CF and non-CF macrophages, both as monocyte-derived macrophages and as lung macrophages. These data strongly suggest that the contribution of ROS to P. aeruginosa killing is not affected by CFTR mutations.

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Section: Resultssupporting

confidence: 90%

Reactive-Oxygen-Species-Mediated P. aeruginosa Killing Is Functional in Human Cystic Fibrosis Macrophages

Cifani¹,

Pompili²,

Anile

et al. 2013

PLoS ONE

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“…Our previous study showed that AquADEKs attenuated selected OS markers in pediatric patients with CF [10]. Lezo et al also reported that CF patients showed elevated OS markers even in stable clinical conditions and with plasma antioxidants within the normal range [8]. …”

Section: Discussionmentioning

confidence: 99%

“…Severe OS increases effects of pathological inflammation in patients with CF [7]. OS increases with age of patients, and its harmful effects can be ameliorated by properly mitigated antioxidant supplementation [8]. It has been suggested that antioxidant status of the patients should be monitored closely and antioxidant supplementation should be considered before significant deficiencies develop to ensure optimum antioxidant protection [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Modification of Proteins in Pediatric Cystic Fibrosis with Bacterial Infections

Sadowska-Bartosz

Galiniak

Bartosz

et al. 2014

Oxidative Medicine and Cellular Longevity

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Pseudomonas aeruginosa and Staphylococcus aureus cause chronic lung infection in cystic fibrosis (CF) patients, inducing chronic oxidative stress. Several markers of plasma protein oxidative damage and glycoxidation and activities of erythrocyte antioxidant enzymes have been compared in stable CF patients chronically infected with Pseudomonas aeruginosa (n = 12) and Staphylococcus aureus (n = 10) in relation to healthy subjects (n = 11). Concentration of nitric oxide was also measured in the exhaled air from the lower respiratory tract of patients with CF. Elevated glycophore (4.22 ± 0.91 and 4.19 ± 1.04 versus control 3.18 ± 0.53 fluorescence units (FU)/mg protein; P < 0.05) and carbonyl group levels (1.9 ± 0.64, 1.87 ± 0.45 versus control 0.94 ± 0.19 nmol/mg protein; P < 0.05) as well as increased glutathione S-transferase activity (2.51 ± 0.88 and 2.57 ± 0.79 U/g Hb versus 0.77 ± 0.16 U/g Hb; P < 0.05) were noted in Pseudomonas aeruginosa and Staphylococcus aureus infected CF. Kynurenine level (4.91 ± 1.22 versus 3.89 ± 0.54 FU/mg protein; P < 0.05) was elevated only in Staphylococcus aureus infected CF. These results confirm oxidative stress in CF and demonstrate the usefulness of the glycophore level and protein carbonyl groups as markers of oxidative modifications of plasma proteins in this disease.

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“…This scenario might at least partly explain why (1) genetic polymorphisms in hepatic metabolizing enzymes are not major predisposing factors Alfirevic et al, 2003;Wolkenstein et al, 2005) and (2) sulfonamide reactions are detected in a higher number of subjects with AIDS and cystic fibrosis (van der Ven et al, 1994a;Lavergne et al, 2010) where oxidative stress plays an important role in the disease pathogenesis (van der Ven and Boers, 1997; Walmsley et al, 1997;Lezo et al, 2013). Nitroso SMX stimulates innate immunity through the activation of dendritic cells (Sanderson et al, 2007) and adaptive immunity through the generation of protein adducts.…”

Section: The Antigenicity and Immunogenicity Of Drugs That Acquirementioning

confidence: 99%

Idiosyncratic Adverse Drug Reactions: Current Concepts

2013

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Oxidative stress in stable cystic fibrosis patients: Do we need higher antioxidant plasma levels?

Abstract: The majority of patients showed elevated plasma chromolipids that increased with age. Antioxidant vitamin reference ranges provide incomplete information on the redox status. CF patients with PI showed excessive oxidative stress damage.

Cited by 27 publications

References 27 publications

Reactive-Oxygen-Species-Mediated P. aeruginosa Killing Is Functional in Human Cystic Fibrosis Macrophages

Reactive-Oxygen-Species-Mediated P. aeruginosa Killing Is Functional in Human Cystic Fibrosis Macrophages

Oxidative Modification of Proteins in Pediatric Cystic Fibrosis with Bacterial Infections

Idiosyncratic Adverse Drug Reactions: Current Concepts

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