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

The role of exercise-induced oxidative stress in the reduced quadriceps endurance of chronic obstructive pulmonary disease (COPD) patients has never been shown. We conducted a randomized, double-blind, and crossover study in which nine severe patients performed localized dynamic quadriceps endurance tests at 40% of maximal strength after oral treatment with the antioxidant, N-acetylcysteine (NAC), and placebo. Venous blood was sampled before, immediately after exercise, and 6 hours later. Endurance time improved by 25% after NAC treatment compared with placebo (p < 0.05). Superoxide anion (oxidant) release by stimulated phagocytes decreased after treatment (p < 0.05). No change in the antioxidant system was observed. Lipid peroxidation, an index of oxidative stress, was significantly increased 6 hours after exercise in the placebo condition (p < 0.05) but not after treatment. Advanced oxidized protein products, another index of oxidative stress, were also increased 6 hours after exercise by 139 +/- 27% in the placebo condition but only by 54 +/- 19% after treatment (p < 0.05). This study shows that NAC treatment in COPD reduced basal disturbance in the prooxidant system, improved endurance time, and prevented exercise-induced oxidative stress. Oxidative stress thus seems to be implicated in the reduced quadriceps endurance of patients with COPD.

[1]  A. Bast,et al.  Oxidant metabolism in chronic obstructive pulmonary disease , 2003, European Respiratory Journal.

[2]  L. Koenderman,et al.  Systemic inflammation in chronic obstructive pulmonary disease , 2003, European Respiratory Journal.

[3]  F. Maltais,et al.  Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients with chronic obstructive pulmonary disease. , 2003, American journal of respiratory and critical care medicine.

[4]  E. Wouters,et al.  ROS in the local and systemic pathogenesis of COPD. , 2003, Free radical biology & medicine.

[5]  M. Mador,et al.  Quadriceps fatigability after single muscle exercise in patients with chronic obstructive pulmonary disease. , 2003, American journal of respiratory and critical care medicine.

[6]  V. Callot,et al.  Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema , 2003, European Respiratory Journal.

[7]  S. Hurd,et al.  Global Strategy for the Diagnosis, Management and Prevention of COPD: 2003 update , 2003, European Respiratory Journal.

[8]  S. Hussain,et al.  Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease. , 2003, American journal of respiratory cell and molecular biology.

[9]  François Maltais,et al.  Exercise-induced quadriceps oxidative stress and peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease. , 2003, American journal of respiratory and critical care medicine.

[10]  유상준,et al.  Systemic effects of chronic obstructive pulmonary disease , 2003, European Respiratory Journal.

[11]  A. Varray,et al.  Evidence of local exercise-induced systemic oxidative stress in chronic obstructive pulmonary disease patients , 2002, European Respiratory Journal.

[12]  Y. Lacasse,et al.  Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. , 2002, American journal of respiratory and critical care medicine.

[13]  M. Mador Muscle mass, not body weight, predicts outcome in patients with chronic obstructive pulmonary disease. , 2002, American journal of respiratory and critical care medicine.

[14]  W. Bailey,et al.  Global initiative for chronic obstructive lung disease. , 2002, Journal of cardiopulmonary rehabilitation.

[15]  J. Taguchi,et al.  Increased level of advanced oxidation protein products in patients with coronary artery disease. , 2002, Atherosclerosis.

[16]  C. Delcourt,et al.  Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[17]  J. Barberà,et al.  Reduced muscle redox capacity after endurance training in patients with chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[18]  S. Hurd,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. , 2001, American journal of respiratory and critical care medicine.

[19]  M. Janiszewski,et al.  Inhibition of vascular NADH/NADPH oxidase activity by thiol reagents: lack of correlation with cellular glutathione redox status. , 2000, Free radical biology & medicine.

[20]  P. Leuenberger,et al.  Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. , 2000, Clinical therapeutics.

[21]  J. Viña,et al.  Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[22]  W. MacNee,et al.  Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[23]  D. Postma,et al.  The many faces of airway inflammation. Asthma and chronic obstructive pulmonary disease. Asthma Research Group. , 1999, American journal of respiratory and critical care medicine.

[24]  P. Jungers,et al.  Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. , 1998, Journal of immunology.

[25]  F. Maltais,et al.  Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[26]  Kelly Gs Clinical applications of N-acetylcysteine. , 1998 .

[27]  A. Varray,et al.  Impaired skeletal muscle endurance related to physical inactivity and altered lung function in COPD patients. , 1998, Chest.

[28]  A. Varray,et al.  Improved skeletal muscle performance after individualized exercise training in patients with chronic obstructive pulmonary disease. , 1997, Journal of cardiopulmonary rehabilitation.

[29]  J. Sastre,et al.  Exercise causes blood glutathione oxidation in chronic obstructive pulmonary disease: prevention by O2 therapy. , 1996, Journal of applied physiology.

[30]  C. Léger,et al.  Red blood cell vitamin E concentrations in fetuses are related to but lower than those in mothers during gestation , 1995 .

[31]  M. Reid,et al.  N-acetylcysteine inhibits muscle fatigue in humans. , 1994, The Journal of clinical investigation.

[32]  P. Chanez,et al.  Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients. , 1994, The European respiratory journal.

[33]  W. MacNee,et al.  Effect of N-acetyl cysteine on the concentrations of thiols in plasma, bronchoalveolar lavage fluid, and lung tissue. , 1994, Thorax.

[34]  B. Halliwell,et al.  Lipid peroxidation: its mechanism, measurement, and significance. , 1993, The American journal of clinical nutrition.

[35]  M. Holdiness Clinical Pharmacokinetics of N-Acetylcysteine , 1991, Clinical pharmacokinetics.

[36]  G. Sjøgaard,et al.  Dynamic knee extension as model for study of isolated exercising muscle in humans. , 1985, Journal of applied physiology.

[37]  G. Brooks,et al.  Free radicals and tissue damage produced by exercise. , 1982, Biochemical and biophysical research communications.

[38]  K. Yagi,et al.  A simple fluorometric assay for lipoperoxide in blood plasma. , 1976, Biochemical medicine.

[39]  C. Sen,et al.  Handbook of oxidants and antioxidants in exercise , 2000 .

[40]  E. Wouters,et al.  Altered glutamate metabolism is associated with reduced muscle glutathione levels in patients with emphysema. , 2000, American journal of respiratory and critical care medicine.

[41]  Derick Han,et al.  Part VII • Chapter 17 – Oxidative stress indices: analytical aspects and significance , 2000 .

[42]  M. Reid,et al.  Part IX • Chapter 22 – Muscle fatigue: mechanisms and regulation , 2000 .

[43]  C. Rice-Evans,et al.  Total antioxidant status in plasma and body fluids. , 1994, Methods in enzymology.