Nitrosative and Oxidative Stress, Reduced Antioxidant Capacity, and Fiber Type Switch in Iron-Deficient COPD Patients: Analysis of Muscle and Systemic Compartments

Abstract

We hypothesized that a rise in the levels of oxidative/nitrosative stress markers and a decline in antioxidants might take place in systemic and muscle compartments of chronic obstructive pulmonary disease (COPD) patients with non-anemic iron deficiency. In COPD patients with/without iron depletion (n = 20/group), markers of oxidative/nitrosative stress and antioxidants were determined in blood and vastus lateralis (biopsies, muscle fiber phenotype). Iron metabolism, exercise, and limb muscle strength were assessed in all patients. In iron-deficient COPD compared to non-iron deficient patients, oxidative (lipofuscin) and nitrosative stress levels were greater in muscle and blood compartments and proportions of fast-twitch fibers, whereas levels of mitochondrial superoxide dismutase (SOD) and Trolox equivalent antioxidant capacity (TEAC) decreased. In severe COPD, nitrosative stress and reduced antioxidant capacity were demonstrated in vastus lateralis and systemic compartments of iron-deficient patients. The slow- to fast-twitch muscle fiber switch towards a less resistant phenotype was significantly more prominent in muscles of these patients. Iron deficiency is associated with a specific pattern of nitrosative and oxidative stress and reduced antioxidant capacity in severe COPD irrespective of quadriceps muscle function. In clinical settings, parameters of iron metabolism and content should be routinely quantify given its implications in redox balance and exercise tolerance.