Role of iron in oxidative stress in skeletal muscle atrophied by immobilization

Abstract

To clarify the role of iron in oxidative stress in skeletal muscle atrophied by immobilization, we investigated the effect of deferoxamine--an iron-chelating agent. Deferoxamine, iron-saturated deferoxamine and double-distilled water (control) were administered subcutaneously from the 4th day after immobilization via osmotic pumps to male Wistar rats (14 weeks old), one ankle joint of which was immobilized in the extended position. After 12 days' immobilization, soleus--typical slow red muscles were collected from both hind limbs and their levels of thiobarbituric acid-reactive substance (TBARS) and glutathione were measured. Deferoxamine suppressed the increase of TBARS and glutathione disulfide in atrophied muscle while iron-saturated deferoxamine did not, which strongly suggests that the iron-chelating action of deferoxamine suppressed the increased oxidative stress. This means that iron plays a very important role in increasing oxidative stress in atrophied muscle. In addition, deferoxamine decreased the degree of atrophy, an effect thought to be mediated by the suppression of oxidative stress.

Oxidative stress during recovery from muscle atrophy

“…We have found an increased iron level, especially in the microsomal fraction, in skeletal muscle atrophied by immobilization, and have suggested the possibility that increased iron may be responsible for the enhanced oxidative stress in atrophied muscle [4,5]. The role of iron has, since, been confirmed by the use of deferoxamine, an iron-chelating agent, which was shown to suppress the increased oxidative stress [6].…”

Mechanistic Links Between Oxidative Stress and Disuse Muscle Atrophy

“…However, many human and animal studies now indicate that oxidative injury occurs in muscle fibers during periods of disuse in locomotor skeletal muscles (10,31,32,34) and in the diaphragm during prolonged mechanical ventilation (25,36). At present, we do not have a complete understanding of the oxidant producing pathways that are responsible for inactivity-induced oxidative stress in skeletal muscles.…”

Cellular Degradation Machineries in Age-Related Loss of Muscle Mass (Sarcopenia)

“…Iron-loading increases the risk for common hallmarks of aging such as DNA damage, protein oxidation and misfolding, and lipid peroxidation and may accelerate the accumulation of lipofuscin (see above). Iron-load is not exclusive to aging-related muscle wasting, but is also evident in experimental disuse atrophy (Kondo et al, 1992) and iron-restriction has been shown to be beneficiary in certain inherited myopathies (Bornman et al, 1998).…”