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.

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To clarify the mechanism of oxidative stress in skeletal muscle atrophied by immobilization, we investigated the change of antioxidant enzyme activities in a typical slow red muscle, the soleus. Atrophied soleus muscles were collected from male Wistar rats (16 weeks old), one ankle joint of which had been immobilized in the fully extended position for 7 days. Also, soleus muscles were collected from intact age-matched rats as control. The activities of Mn-containing superoxide dismutase (Mn-SOD), Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase (GST), catalase, and glutathione reductase (GSSGRx) were measured. The activities of Cu,Zn-SOD, GST, and GSSGRx were significantly higher in atrophied muscles, while the others were unchanged. Increased Cu,Zn-SOD and unchanged Mn-SOD levels might reflect increased generation of superoxide anions in the cytoplasm rather than in the mitochondria. Owing to the enhancement of Cu,Zn-SOD and the unaltered Se-GSHPx and catalase activities, hydrogen peroxide is thought to be increased in the cytoplasm. Because there is also an increase of iron in the microsomes of atrophied muscles, the production of hydroxyl radicals, the most aggressive of radicals, might consequently be elevated.

Oxidative stress is known to cause free radical reactions such as lipid peroxidation, which have a role in damaging biological structures and cellular functions. Exhaustive exercise has been shown to increase levels of lipid peroxidation in skeletal muscle, which is generally thought to be related to the pathogenesis of exercise myopathy (Davies et al. 1982). However there has been few reports on the level of lipid peroxide in atrophied muscle. In this study we report the increased oxidative stress in skeletal muscle atrophied by immobilization. In addition, we shed light on the effect of Vitamin E -an antioxidant on the muscular atrophy to clarify whether such oxidative stress played a role in the onset of muscle proteolysis or not.Fifteen male Wistar rats (14 weeks old) were used; 5 rats for lipid peroxidation, and 10 rats for the effect of Vitamin E. The latter 10 rats were divided into two groups of 5 rats and were injected intraperitoneally either placebo or Vitamin E, once daily for 6 days before immobilization and every other day during immobilization. Vitamin E was given in the form of alpha-tocopherol solubilized in 10% polyoxyethylene hydrogenerated caster oil/lO yo propylene glycol

Hexadecanaphthalenes (S,S,S,S,S,S,S,S,S,S,S,S,S,S,S)-4b and (S,S,S,S,S,S,S,R,S,S,S,S,S,S,S)-4b that possess two tetraphenylporphyrins (TPP) on the upper and lower naphthalene rings were synthesized. Long-range exciton-coupled CD in the Soret region of TPP (about 66 A) was observed. [structure: see text]