Résumé :
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INTRODUCTION A strategy for treating Duchenne muscular dystrophy (DMD) is to compensate for the absence of dystrophin by up-regulation of utrophin, a homologous cytoskeletal protein. OBJECTIFS One potential approach to up-regulate utrophin expression is through stimulation of the nitric oxide (NO) pathway. We addressed the effect of this strategy of treatment on weight of mdx mice, a mouse model for DMD. MÉTHODES Adult mdx mice were approximately 8 weeks old at the start of experiments. Treatment was administered by intraperitoneal injection. Two protocols were used. For a continuous injection protocol, adult animals assigned to the vehicle groups were injected with saline (NaCl 0.9%) and the treated groups were injected with arginine or derivatives at various doses, during 6 weeks. For the pulse injection protocol mice were treated for 4 days one week over 2 during the 6 weeks. All animals were weighed before each injection. RÉSULTATS The normalized weight of treated adult mdx mice appeared to increase after both, continuous and pulse, modes of administration when compared to control mdx mice. This increase was also associated with an increase in the mass of individual studied muscles. This effect is consistent with the anabolic effect of Larginine on muscles. DISCUSSION The use of pharmacological activators of the NO pathway, to improve dystrophic phenotypes has been confirmed by multiple studies in mdx mice. Along with the beneficial up regulation of utrophin, the NO pathway is thought to have additional advantageous effects on muscle health including inducing vasodilatation required for effective supply of metabolites and oxygen to working muscle, activating satellite cells and decreasing muscle inflammation. CONCLUSION Our data allow anticipating a good tolerance profile of these compounds in DMD patients.
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