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

Background: A physiological increase in muscle glutathione after training is not seen in patients with chronic obstructive pulmonary disease (COPD), indicating abnormal peripheral muscle adaptations to exercise. Objective: We hypothesized that oxidative stress is primarily associated with low body mass index (BMI). Methods: Eleven patients with preserved BMI (BMI_N: 28.2 ± 1.2 kg·m^-2), 9 patients with low BMI (BMI _L: 19.7 ± 0.60 kg·m^-2) and 5 age-matched controls (26.5 ± 0.9 kg·m^-2) were studied before and after 8 weeks of high-intensity endurance training. Reduced glutathione (GSH) and γ-glutamyl cysteine synthase heavy-subunit chain mRNA expression (γGCS-HS mRNA) were measured in the vastus lateralis. Results: After training, exercise capacity increased (ΔVO₂PEAK, 13 ± 5.2%; 10 ± 5.6% and 15 ± 4.3% in BMI_L, BMI_N and controls, respectively; p < 0.05 each). GSH levels decreased in BMI _L (from 5.2 ± 0.7 to 3.7 ± 0.8 nmol/mg protein, ΔGSH -1.5 ± 0.7 nmol/mg protein, p < 0.05); no changes were seen in BMI_N (from 5.4 ± 0.7 to 6.7 ± 0.9 nmol/mg protein, ΔGSH 1.3 ± 0.9 nmol/mg protein), whereas GSH markedly increased in controls (from 4.6 ± 1 to 8.7 ± 0.4 nmol/mg protein, ΔGSH 4.1 ± 1 nmol/mg protein, p < 0.01). ΔGSH in BMI_L was different from ΔGSH in BMI_N and controls (p < 0.05, each). Consistent changes were observed in γGCS-HS mRNA expression. Conclusions: GSH depletion after training in BMI_L may suggest that oxidative stress plays a key role in muscle wasting in COPD patients.