Résumé :
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Communication n° 435 Duchenne Muscular Dystrophy (DMD) is a frequent inherited muscular disorder which is still fatal. DMD patients present with muscular weakness that progress towards paralysis. They usually die in the third decade because of respiratory or cardiac failure. DMD is caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that normally contributes in the stabilization of the muscle fibre membrane during muscle activity. In DMD dystrophin is absent leading to numerous cell dysfunctions that culminate in muscle cell necrosis. Subsequently, an inflammatory response develops in the necrotic muscle tissue resulting in increased oxidative stress, responsible for secondary tissue damage. In the mdx dystrophic mouse, both inflammatory response and oxidative stress has been identified as aggravating factors for the course of the disease. Indeed, we have shown previously that Green Tea Extract (GTE), a mixture of powerful antioxidant polyphenols reduces muscle necrosis in mdx mice. Here, we investigated the ability of higher doses of GTE and of its major component, (-)epigallocatechin gallate (EGCG), in improving mdx5Cv muscle function and histology. Three-week old mdx5Cv mice were fed for either 1 or 5 weeks on control chow or on chow containing GTE or EGCG. Normal mice were used as control. Muscle histology showed that GTE and EGCG given for 1 week reduced muscle necrosis. Electrically evoked mechanical properties of the triceps surae were recorded. Phasic and tetanic forces of treated mice were increased (up to +94%) close to values developed by normal mice. In addition, muscles from treated mice exhibited lowered excitability threshold in a force-frequency assay, and showed improved resistance in a fatigue assay (+30 to +50% of untreated). These results suggest that administration of GTE or EGCG to mdx5Cv mice (i) caused a delay in muscle necrosis, and (ii) stimulated muscle adaptation towards a more resistant phenotype.
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