Oxidants and Skeletal Muscle Function: Physiologic and Pathophysiologic Implications

Abstract

Previous studies have demonstrated that skeletal muscles generate considerable reactive oxygen during intense muscle contraction. However, the significance of this phenomenon and whether it represents normal physiology or pathology are poorly understood. Treatment with exogenous antioxidants suggests that normal redox tone during contraction is influencing ongoing contractile function, both at rest and during intense exercise. This could represent the influence of redox-sensitive proteins responsible for excitation-contraction coupling or redox-sensitive metabolic enzymes. Some conditions associated with intense exercise, such as local tissue hypoxia or elevated tissue temperatures, could also contribute to reactive oxygen production. Evidence that muscle conditioning results in upregulation of antioxidant defenses also suggests a close relationship between reactive oxygen and contractile activity. Therefore, there appears to be a significant role for reactive oxygen in normal muscle physiology. However, a number of conditions may lead to an imbalance of oxidant production and antioxidant defense, and these, presumably, do create conditions of oxidant stress. Ischemia-reperfusion, severe hypoxia, severe heat stress, septic shock, and stretch-induced injury may all lead to oxidant-mediated injury to myocytes, resulting in mechanical dysfunction.

Usefulness of combining intermittent hypoxia and physical exercise in the treatment of obesity

“…In spite of that, there is a general condition of ischemia-reperfusion due to the high voltage generated by the muscles during maximal or submaximal contractions. In other words, there are cycles of hypoxia-hyperoxia [35]. Physical activity leads to an increase in oxygen free radicals, but it is not entirely clear whether the phenomenon linked to free radicals increase is hypoxia or hyperoxia.…”

Inactivity and Inflammation in the Critically Ill Patient

“…Muscles are a source of oxidant synthesis, especially during exercise [53]. Both ROS and NO are necessary for normal skeletal muscle contraction.…”

“…Antioxidants are reduced during disease states common to ICU patients such as COPD, acute lung injury, atherosclerosis, and acute renal failure [43,56,57]. These antioxidants are produced by skeletal muscles [53]. Repetitive training can increase antioxidant synthesis and activity in cells and healthy people [58,59].…”

Participação do estresse oxidativo na disfunção muscular esquelética em ratos diabéticos.

“…A xantina oxidase, presente no interior das mitocôndrias, também é uma fonte produtora de O 2 .-para o tecido muscular, principalmente em seu compartimento vascular e durante fenômenos de hipóxia-reoxigenação (Clanton et al, 1999). Ocorre também expressão e atividade mais elevadas da xantina oxidase no músculo esquelético de animais diabéticos induzidos por estreptozotocina (Bravard et al, 2011).…”

“…Componentes da cadeia de transporte de elétrons, gliceraldeído 3-fosfato desidrogenase e creatina quinase mitocondrial e citossólica também são passíveis de modulação redox (Clanton et al, 1999). Fosfofrutoquinase, piruvato quinase, hexoquinase e glicogênio fosforilase fosfatase são inativadas pelo tratamento com GSSG e outros dissulfetos biológicos (Gilbert, 1982).…”