{'fraction_non_alphanumeric': 0.04440574662603396, 'fraction_numerical': 0.02220287331301698, 'mean_word_length': 5.622478386167147, 'pattern_counts': {'":': 0, '<': 4, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Effects of a mitochondria targeted antioxidant on skeletal muscle mitochondrial function with cigarette smoke exposure and Chronic Obstructive Pulmonary Disease

Reactive oxygen species (ROS) are important signaling molecules in cells. However, the exaggerated free radical production accompanying mitochondrial dysfunction with Chronic Obstructive Pulmonary Disease (COPD) has been suggested to play a crucial role in the development of metabolic abnormalities in these patients. Consequently, selective inhibition of mitochondrial ROS could be a potential therapeutic strategy to restore mitochondrial function and subsequently attenuate exercise‐induced metabolic disturbance during exercise in COPD patients. The goal of this study was therefore to determine the effects of a mitochondria targeted antioxidant, MitoQ, on free radical levels, mitochondrial function, and skeletal muscle metabolism in six patients with moderate to very‐severe COPD and a smoking mouse model (C57/Bl6 exposed to cigarette smoke for 8 months) using electron paramagnetic spectroscopy (EPR), 31P/1H magnetic resonance spectroscopy (1H/31P MRS), high‐resolution respirometry in permeabilized skeletal muscle fiber. 4 weeks of MitoQ supplementation (MQ) decreased blood free radical levels measured by EPR (control, CTL: 4.3 ± 3.3 a.u.; MQ: 1.8 ± 1.7 a.u.; P<0.05). Nevertheless, the exercise‐induced changes in intracellular O2 partial pressure, high‐energy phosphate, and pH measured by 1H/31P MRS in the plantar flexor muscles of patients with COPD were not significantly altered with MitoQ. Also, the peak rate of oxidative ATP synthesis measured by 31P‐MRS was lower with MitoQ (CTL: 19 ± 6 mM.min−1; MQ: 14 ± 4 mM.min−1, P<0.05), suggesting an impaired mitochondrial function in vivo. This finding was further supported by the lower muscle respiratory capacity measured in permeabilized skeletal muscle fibers incubated with MitoQ (−43%, P<0.05) from a smoking mouse model. Specifically, complex I (−42%) and free‐fatty acid (−51%) linked respiration were significantly decreased with MitoQ (P<0.05). Together, these findings suggest that decreasing ROS levels using a mitochondria targeted antioxidant may, in fact, be detrimental to oxidative phosphorylation capacity in the skeletal muscle of COPD patients.