BACKGROUND: In chronic heart failure (CHF), cross-talk between inflammatory activation and oxidative stress has been anticipated in skeletal muscle (SM). The role of the radical scavenger enzymes superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX), which remove oxygen radicals, has never been assessed in the SM in this context. Moreover, it remains unknown whether exercise training augments the activity of these enzymes in CHF. METHODS AND RESULTS: Twenty-three patients with CHF were randomized to either 6 months of exercise training (T) or a sedentary lifestyle (C); 12 age-matched healthy subjects (HS) were studied in parallel. Activity of Cat, SOD, and GPX was assessed in SM biopsies before and after 6 months (6 months). Oxidative stress was determined by measuring nitrotyrosine formation. SOD, Cat, and GPX activity was reduced by 31%, 57%, and 51%, respectively, whereas nitrotyrosine formation was increased by 107% in SM in CHF (p < 0.05 versus HS). In CHF, exercise training augmented GPX and Cat activity in SM by 41% (p < 0.05 versus before and group C) and 42% (p < 0.05 versus before and group C), respectively, and decreased nitrotyrosine production by 35% (from 3.8 +/- 0.4% tissue area before to 2.5 +/- 0.3% after 6 months; p < 0.05 versus before). CONCLUSIONS: The reduced activity of major antioxidative enzymes in the SM of CHF patients is associated with increased local oxidative stress. Exercise training exerts antioxidative effects in the SM in CHF, in particular, due to an augmentation in activity of radical scavenger enzymes.
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