Muscle and blood redox status after exercise training in severe COPD patients

doi:10.1016/j.freeradbiomed.2011.09.022

Free Radical Biology and Medicine

Volume 52, Issue 1, 1 January 2012, Pages 88-94

https://doi.org/10.1016/j.freeradbiomed.2011.09.022 Get rights and content

Abstract

Beneficial effects of exercise training in patients with chronic obstructive pulmonary disease (COPD) are acknowledged. However, high-intensity exercise may enhance muscle oxidative stress in severe COPD patients. We hypothesized that high-intensity exercise training of long duration does not deteriorate muscle redox status. In the vastus lateralis and blood of 18 severe COPD patients and 12 controls, before and after an 8-week training program, protein oxidation and nitration, antioxidant systems, and inflammatory cytokines were examined. At baseline, COPD patients showed greater muscle oxidative stress and superoxide dismutase activity and circulating inflammatory cytokines than controls. Among COPD patients, muscle and blood protein carbonylation levels were correlated. Both groups showed training-induced increase in VO₂ peak and decreased blood lactate levels. After training, among the COPD patients, blood protein nitration levels were significantly reduced and muscle protein oxidation and nitration levels did not cause impairment. Muscle and blood levels of inflammatory cytokines were not modified by training in either patients or controls. We conclude that in severe COPD patients, high-intensity exercise training of long duration improves exercise capacity while preventing the enhancement of systemic and muscle oxidative stress. In addition, in these patients, resting protein oxidation levels correlate between skeletal muscle and blood compartments.

Graphical abstract

Highlights

► High-intensity exercise may enhance muscle oxidative stress in severe COPD patients ► We tested whether exercise training of long duration deteriorates muscle redox status ► In COPD patients, muscle and blood protein oxidation levels were correlated ► Training improved physiological parameters and blood protein nitration in patients ► High-intensity exercise training did not impair muscle oxidative stress in patients

Section snippets

Subjects

We prospectively recruited 18 clinically stable COPD [20] patients and 12 healthy sedentary age-matched controls on an outpatient basis at Hospital Clinic (Barcelona, Spain). All patients with COPD and controls were studied at baseline and after the 8-week exercise training program. The current investigation was designed in accordance with both the ethical standards on human investigation in our institution and the World Medical Association guidelines for research on human beings. The Ethics

Study groups and physiological training effects

On average, COPD patients exhibited a severe disease (Table 1). Aerobic capacity, assessed by peak exercise oxygen uptake (VO₂ peak) and 6-min walking distance, was impaired in the patients with COPD compared to healthy controls (Table 1). Importantly, aerobic capacity as measured by VO₂ peak and R_W peak significantly improved after training in both healthy controls and severe COPD patients (Table 2). Additionally, the distance walked by patients and healthy subjects after the training was

Discussion

These results clearly demonstrate the main hypothesis of the investigation, providing evidence that a standard (8 weeks) endurance exercise training program does not enhance oxidative stress levels in either limb muscles or blood of patients with severe COPD. It should also be noted that after training in these patients, blood protein nitration levels were, indeed, significantly lower compared to baseline. Moreover, levels of oxidative stress in the two compartments (muscles and blood) showed a

Conclusions

We conclude that in severe COPD patients, high-intensity exercise training of long duration improves exercise capacity while preventing the enhancement of systemic and muscle oxidative stress. In addition, in these patients, resting protein oxidation levels correlate between skeletal muscle and blood compartments.

Acknowledgments

We thank Philip Muñoz, Yolanda Torralba, Anael Barberan, and the technical staff of the Lung Function Laboratory at Hospital Clinic for their support in the studies. This study was supported by the European Commission (FP6) Biobridge (LSHG-CT-2006-037939), Fundació Marató TV3-042010 and TV3-071010, Fondo de Investigaciones Sanitarias (FIS-PI061510), CIBERES (CB-06/06), ISCIII-RTICC (RD06/0020/0046), Comissionat per a Universitats i Recerca de la Generalitat de Catalunya (2009SGR1308,

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Ageing, a sedentary lifestyle, and obesity are associated with increased oxidative stress, while regular exercise is associated with an increased antioxidant capacity in trained skeletal muscles. Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO₂max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO₂max, age and adiposity differences. Multiple regression analysis indicates that the VO₂max in mL.kg LLM⁻¹.min^⁻¹can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO₂max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO₂max and body fat percentage. Overweight and obesity were associated with increased pSer⁴⁰-Nrf2, pSer⁴⁰-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO₂max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.
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Citation Excerpt :
However, included studies did not report correlation coefficients between protein carbonyls and clinically relevant outcomes. In other chronic health conditions, oxidative damage to proteins is a significant contributor to skeletal muscle dysfunction [103], with reports showing elevated concentrations of protein carbonylation and nitration in the blood and skeletal muscle of people with chronic obstructive pulmonary disease [104]. Such associations could have implications in the skeletal muscle dysfunction which characterise CF [105].
Oxidative stress may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to quantify CF-related redox imbalances.
Systematic searches of the Medline, CINAHL, CENTRAL and PsycINFO databases were conducted. Mean content of blood biomarkers from people with clinically-stable CF and non-CF controls were used to calculate the standardized mean difference (SMD) and 95% confidence intervals (95% CI).
Forty-nine studies were eligible for this review including a total of 1792 people with CF and 1675 controls. Meta-analysis revealed that protein carbonyls (SMD: 1.13, 95% CI: 0.48 to 1.77), total F₂-isoprostane 8-iso-prostaglandin F_2α (SMD: 0.64, 95% CI: 0.23 to 1.05) and malondialdehyde (SMD: 1.34, 95% CI: 0.30 to 2.39) were significantly higher, and vitamins A (SMD: −0.66, 95% CI -1.14 to −0.17) and E (SMD: −0.74, 95% CI: −1.28 to −0.20), β-carotene (SMD: −1.80, 95% CI: −2.92 to −0.67), lutein (SMD: −1.52, 95% CI: −1.83 to −1.20) and albumin (SMD: −0.98, 95% CI: −1.68 to −0.27) were significantly lower in the plasma or serum of people with CF versus controls.
This systematic review and meta-analysis found good evidence for reduced antioxidant capacity and elevated oxidative stress in people with clinically-stable CF.
Impact of Physical Activity and Exercise on Chronic Obstructive Pulmonary Disease Phenotypes: The Relevance of Muscle Adaptation
2019, Archivos de Bronconeumologia
Role of Nrf2 and exercise in alleviating COPD-induced skeletal muscle dysfunction
2023, Therapeutic Advances in Respiratory Disease
Residual effects of 12 weeks of power-oriented resistance training plus high-intensity interval training on muscle dysfunction, systemic oxidative damage, and antioxidant capacity after 10 months of training cessation in older people with COPD
2023, Scandinavian Journal of Medicine and Science in Sports

View all citing articles on Scopus

¹: These authors contributed equally to this work.

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Original ContributionMuscle and blood redox status after exercise training in severe COPD patients

Abstract

Graphical abstract

Highlights

Section snippets

Subjects

Study groups and physiological training effects

Discussion

Conclusions

Acknowledgments

Chest

Methods Enzymol.

Trends Endocrinol. Metab.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease: a statement of the American Thoracic Society and European Respiratory Society

Am. J. Respir. Crit. Care Med.

Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease

Am. J. Respir. Cell Mol. Biol.

Chronic endurance exercise induces quadriceps nitrosative stress in patients with severe COPD

Thorax

Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease

Am. J. Physiol.

Reactive oxygen species and redox-regulation of skeletal muscle adaptations to exercise

Philos. Trans. R. Soc. Lond. B Biol. Sci.

Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease?

Am. J. Respir. Crit. Care Med.

Reduced muscle redox capacity after endurance training in patients with chronic obstructive pulmonary disease

Am. J. Respir. Crit. Care Med.

Training depletes muscle glutathione in patients with chronic obstructive pulmonary disease and low body mass index

Respiration

Systemic manifestations and comorbidities of COPD

Eur. Respir. J.

Systemic and local inflammation in asthma and chronic obstructive pulmonary disease: is there a connection?

Proc. Am. Thorac. Soc.

Cytokine profile in quadriceps muscles of patients with severe COPD

Thorax

Complex chronic comorbidities of COPD

Eur. Respir. J.

Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease

Am. J. Respir. Crit. Care Med.

Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive pulmonary disease

Am. J. Respir. Crit. Care Med.

The anti-inflammatory effect of exercise

J. Appl. Physiol.

Original Contribution
Muscle and blood redox status after exercise training in severe COPD patients