Résumé :
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Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate (EGCG), a major polyphenol of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5mg/kg body weight in saline) was injected subcutaneously four times a week into the backs of C57BL/10 normal mice and dystrophin-deficient mdx mice for 8 weeks from either the day of birth or a day after birth. Saline was injected into normal and mdx controls. At the end of the treatment EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology and electrophysiology of the treated mdx mice. First, the activities of serum creatine kinase, an index of muscle damage, were reduced to near normal levels. Second, the numbers per unit volume of an oxidative stress marker, autofluorescent lipofuscin granules, in soleus and diaphragm muscles were significantly decreased by about 50 % compared to the numbers in the corresponding saline-treated controls. Third, in sections of diaphragm muscles, the relative area of histologically normal muscle fibres increased significantly about 2-fold whereas the relative areas of connective tissue and necrotic muscle fibres were significantly reduced by about 40 and 90% respectively. In sections of soleus muscles the relative area of normal muscle fibres significantly increased about 1.5-fold but that of necrotic muscle fibres decreased by 95 %. Fourth, the times for the maximum tetanic force of soleus muscles to fall by a half increased to almost normal values. Our study corroborates other recent studies that EGCG is effective for limiting the onset of muscular dystrophy in mdx mice without causing side effects.
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