From muscle disuse to myopathy in COPD: potential contribution of oxidative stress

Abstract

Evidence has been accumulating that chronic inactivity leading to muscle disuse is unlikely to be the only explanation for the peripheral muscle dysfunction of chronic obstructive pulmonary disease (COPD) patients.Although a new concept of myopathy was recently proposed, the question of disuse and/or a form of myopathy is still being debated. This review proposes definitions for the terms used in this debate, discusses the relevant studies and concludes that the evidence points to a myopathy associated with muscle disuse in COPD.COPD myopathy implies pharmacological and/or pathophysiological mechanisms that need to be identified in order to optimally orient therapeutic strategies. The literature indicates that corticosteroids, inflammation, hypoxaemia and oxidative stress are among the factors contributing to COPD muscle dysfunction, but their relative contributions have not been fully elucidated.This review presents the advances in understanding each of these mechanisms, especially the data showing that muscle oxidative stress occurs and contributes to muscle dysfunction in chronic obstructive pulmonary disease. The current review also reports the studies that have elucidated the molecular mechanisms underlying this stress in chronic obstructive pulmonary disease by demonstrating alterations in oxidant and/or antioxidant systems. Finally, the review considers how inflammation and hypoxaemia may trigger oxidative stress in chronic obstructive pulmonary disease muscles and presents the therapeutic modalities that should be proposed to prevent it.

Incapacity, Handicap, and Oxidative Stress Markers of Male Smokers With and Without COPD

“…72 Oxidative stress is known as a major cause of myopathy in subjects with COPD. 67,73 The present paper supports this hypothesis, since the COPD group, when compared with the non-COPD group, has a lower glutathione level (Fig. 1B).…”

“…67 It could be the result of numerous alterations, with the main ones being corticosteroid use, sedentary lifestyle, oxidative stress, inflammation, and apoptosis. 68 The corticosteroidinduced myopathy 69 hypothesis is not retained, since corticosteroid use was a non-inclusion criterion.…”

Myostatin up-regulation is associated with the skeletal muscle response to hypoxic stimuli

“…A c c e p t e d M a n u s c r i p t 5 among others, of peripheral muscle dysfunction in this disease (Couillard and Prefaut, 2005;Gosker et al, 2002). However, the exact mechanisms underlying skeletal muscle dysfunction in COPD remain unclear.…”

“…Collectively our data tend to implicate the hypoxic regulation of myostatin in patients with COPD and suggest that myostatin induction could be related to the presence of COPD itself rather to muscle atrophy. However, it should be noted that, in addition to hypoxaemia, several factors including inflammation, oxidative stress have been implicated in muscle limb dysfunction in COPD (Couillard and Prefaut, 2005). It is thus conceivable that inflammation and oxidative stress may also contribute alone or in concert with hypoxaemia to the higher myostatin expression levels.…”

Efeitos sistêmicos da hipoxemia noturna em pacientes com doença pulmonar obstrutiva crônica sem síndrome da apnéia obstrutiva do sono

“…(1) Consequently, such patients can present strong indications of concomitant systemic inflammation associated with the bronchial inflammatory process, capable of inducing abnormal oxidative stress, (2,3) which can be exacerbated by chronic daytime hypoxemia. (4) However, the systemic effects of nocturnal hypoxemia have been little studied in patients with COPD.…”