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Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD.

Dove RE, Leong-Smith P, Roos-Engstrand E, Pourazar J, Shah M, Behndig AF, Mudway IS, Blomberg A - Eur Clin Respir J (2015)

Bottom Line: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers.In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden ; MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.

ABSTRACT

Background: Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke.

Methods: Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13).

Results: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.

Conclusions: We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.

No MeSH data available.


Related in: MedlinePlus

Total Vitamin C, ascorbate, and dehydroascorbate concentrations in bronchoalveolar lavage fluids recovered from healthy never smokers, smokers with normal lung function, COPD ex-smokers, and COPD smokers. Details of boxplots and statistical analysis are as described in Fig. 1.
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Figure 0002: Total Vitamin C, ascorbate, and dehydroascorbate concentrations in bronchoalveolar lavage fluids recovered from healthy never smokers, smokers with normal lung function, COPD ex-smokers, and COPD smokers. Details of boxplots and statistical analysis are as described in Fig. 1.

Mentions: Vitamin C concentrations were significantly augmented in BAL fluid in smokers with normal lung function, compared with healthy non-smoking controls (1.8-fold – Fig. 2). An increase (2.1-fold) was also observed in the COPD smoking group compared with the COPD ex-smokers, but this failed to attain statistical significance. These increases were only related to the subjects’ smoking status and not the presence of COPD. In the COPD patients, the significant increase in BAL fluid vitamin C concentrations with smoking reflected an increase in ascorbate (Fig. 2), though it was notable that ascorbate itself contributed only to a small fraction of the measured vitamin C pool and was often not measureable in the ex- or never smoking subjects. No evidence of altered BAL fluid urate concentrations was observed related to either smoking status or COPD diagnosis: 0.48 (0.28–0.70) µM – healthy never smoking controls, versus 0.41 (0.30–0.87) µM – smokers with normal lung function; 0.54 (0.35–0.75) µM – COPD ex-smokers, versus 0.66 (0.36–0.83) µM – COPD smokers.


Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD.

Dove RE, Leong-Smith P, Roos-Engstrand E, Pourazar J, Shah M, Behndig AF, Mudway IS, Blomberg A - Eur Clin Respir J (2015)

Total Vitamin C, ascorbate, and dehydroascorbate concentrations in bronchoalveolar lavage fluids recovered from healthy never smokers, smokers with normal lung function, COPD ex-smokers, and COPD smokers. Details of boxplots and statistical analysis are as described in Fig. 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4629722&req=5

Figure 0002: Total Vitamin C, ascorbate, and dehydroascorbate concentrations in bronchoalveolar lavage fluids recovered from healthy never smokers, smokers with normal lung function, COPD ex-smokers, and COPD smokers. Details of boxplots and statistical analysis are as described in Fig. 1.
Mentions: Vitamin C concentrations were significantly augmented in BAL fluid in smokers with normal lung function, compared with healthy non-smoking controls (1.8-fold – Fig. 2). An increase (2.1-fold) was also observed in the COPD smoking group compared with the COPD ex-smokers, but this failed to attain statistical significance. These increases were only related to the subjects’ smoking status and not the presence of COPD. In the COPD patients, the significant increase in BAL fluid vitamin C concentrations with smoking reflected an increase in ascorbate (Fig. 2), though it was notable that ascorbate itself contributed only to a small fraction of the measured vitamin C pool and was often not measureable in the ex- or never smoking subjects. No evidence of altered BAL fluid urate concentrations was observed related to either smoking status or COPD diagnosis: 0.48 (0.28–0.70) µM – healthy never smoking controls, versus 0.41 (0.30–0.87) µM – smokers with normal lung function; 0.54 (0.35–0.75) µM – COPD ex-smokers, versus 0.66 (0.36–0.83) µM – COPD smokers.

Bottom Line: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers.In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden ; MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.

ABSTRACT

Background: Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke.

Methods: Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13).

Results: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.

Conclusions: We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.

No MeSH data available.


Related in: MedlinePlus