title: Dichloroacetate modulates the oxidative stress and inflammatory response to exercise in COPD.
abstract: BACKGROUND
  Impaired skeletal muscle function contributes to exercise intolerance in patients with COPD. Exercise-induced oxidative stress may initiate or accelerate impaired muscle function. Dichloroacetate (DCA) activates muscle pyruvate dehydrogenase complex (PDC) at rest, reducing inertia in mitochondrial energy delivery at the onset of exercise and thereby diminishing anaerobic energy production. This study aimed to determine whether DCA infusion also may reduce exercise-induced systemic oxidative stress and inflammatory response in patients with COPD.
  
  
  METHODS
  A randomized, double-blind crossover design was used in which 13 patients with COPD performed maximal cycle exercise after an IV infusion of DCA (50 mg/kg body mass) or saline solution (placebo). Venous blood was sampled before exercise, and immediately, 30 min, and 2 h after exercise. Urine samples were obtained before and 2 h after exercise.
  
  
  RESULTS
  Peak workload improved significantly after DCA infusion compared to placebo (10%; p < 0.01). Urinary uric acid levels after exercise were significantly lower in the DCA condition than in the placebo condition, whereas no significant difference was observed for urinary malondialdehyde levels. Oxidized glutathione (GSSG) levels were significantly increased 2 h after exercise in the placebo condition (p < 0.02) but not after DCA infusion. No changes in reduced glutathione (GSH), GSSG/GSH ratio, and superoxide dismutase activity were observed. Plasma interleukin (IL)-6 levels significantly increased 2 h after exercise only in the DCA condition (p < 0.01).
  
  
  CONCLUSIONS
  This study shows that improved performance after a pharmacologic intervention known to activate PDC was accompanied by an enhanced IL-6 response and a limited reduction in exercise-induced systemic oxidative stress.
authors.affiliation: Departments of Respiratory Medicine, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands. Electronic address: e.mercken@pul.unimaas.nl.
authors.forename: Evi M
authors.initials: EM
authors.lastname: Mercken
authors.affiliation: Department of Respiratory Medicine, Institute for Lung Health, University Hospitals of Leicester National Health Service Trust, Leicester, UK.
authors.forename: Lori D
authors.initials: LD
authors.lastname: Calvert
authors.affiliation: Department of Respiratory Medicine, Institute for Lung Health, University Hospitals of Leicester National Health Service Trust, Leicester, UK.
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Singh
authors.affiliation: Health Risk Analysis and Toxicology, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Geja J
authors.initials: GJ
authors.lastname: Hageman
authors.affiliation: Departments of Respiratory Medicine, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Annemie M
authors.initials: AM
authors.lastname: Schols
authors.affiliation: Department of Respiratory Medicine, Institute for Lung Health, University Hospitals of Leicester National Health Service Trust, Leicester, UK.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Steiner
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001823:Body Composition; D018592:Cross-Over Studies; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D013147:Spirometry; D014527:Uric Acid / Q000652:urine
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D010919:Placebos; D014527:Uric Acid; D008315:Malondialdehyde; D003999:Dichloroacetic Acid; D005978:Glutathione