title: Arginine butyrate per os protects mdx mice against cardiomyopathy, kyphosis and changes in axonal excitability.
abstract: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by lack of dystrophin, a sub-sarcolemmal protein, which leads to dramatic muscle deterioration. We studied in mdx mice, the effects of oral administration of arginine butyrate (AB), a compound currently used for the treatment of sickle cell anemia in children, on cardiomyopathy, vertebral column deformation and electromyographic abnormalities. Monthly follow-up by echocardiography from the 8th month to the 14th month showed that AB treatment protected the mdx mice against drastic reduction (20-23%) of ejection fraction and fractional shortening, and also against the ≈20% ventricular dilatation and 25% cardiac hypertrophy observed in saline-treated mdx mice. The phenotypic improvement was corroborated by the decrease in serum CK level and by better fatigue resistance. Moreover, AB treatment protected against the progressive spinal deformity observed in mdx mice, another similarity with DMD patients. The value of the kyphosis index in AB-treated mice reached 94% of the value in C57BL/10 mice. Finally, axonal excitability parameters such as the membrane resting potential, the threshold and amplitude of the action potential, the absolute and relative refractory periods and the supernormal and subnormal periods, recorded from caudal and plantar muscles in response to excitability tests, that were modified in saline-treated mdx mice were not significantly changed, compared with wild-type animals, in AB-treated mdx mice. All of these results suggest that AB could be a potential treatment for DMD patients.
authors.affiliation: CNRS, Institut de Neurobiologie Alfred Fessard, FRC2118, Neurobiologie & Développement, UPR 3294, Gif sur Yvette, F-91198, France. Electronic address: sara.vianello@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Vianello
authors.affiliation: UPMC, Université Paris 6, UMR 974, Institut de Myologie, F-75013 Paris, France. Electronic address: s.bouyon@hotmail.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bouyon
authors.affiliation: CNRS, Institut de Neurobiologie Alfred Fessard, FRC2118, Neurobiologie & Développement, UPR 3294, Gif sur Yvette, F-91198, France. Electronic address: evelyne.benoit@inaf.cnrs-gif.fr.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Benoit
authors.affiliation: CNRS, IR4M-UMR8081, Orsay, F-91405, France. Electronic address: catherine.sebrie@u-psud.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sebrié
authors.affiliation: CNRS, Institut de Neurobiologie Alfred Fessard, FRC2118, Neurobiologie & Développement, UPR 3294, Gif sur Yvette, F-91198, France. Electronic address: boerio_delphine@yahoo.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Boerio
authors.affiliation: CNRS, Muséum National d'Histoire Naturelle, CNRS, UMR7179, Pavillon d'anatomie comparée, BP 55, 52 Rue Cuvier, 75231 Paris Cedex 05, France. Electronic address: herbin@mnhn.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Herbin
authors.affiliation: CNRS, Institut de Neurobiologie Alfred Fessard, FRC2118, Neurobiologie & Développement, UPR 3294, Gif sur Yvette, F-91198, France. Electronic address: roulot@ipmc.cnrs.fr.
authors.forename: Morgane
authors.initials: M
authors.lastname: Roulot
authors.affiliation: UPMC, Université Paris 6, UMR 974, Institut de Myologie, F-75013 Paris, France; ONIRIS, Centre de Boisbonne, Nantes F-44307, France. Electronic address: yves.fromes@gmail.com.
authors.forename: Yves
authors.initials: Y
authors.lastname: Fromes
authors.affiliation: CNRS, Institut de Neurobiologie Alfred Fessard, FRC2118, Neurobiologie & Développement, UPR 3294, Gif sur Yvette, F-91198, France. Electronic address: sabine.delaporte@inaf.cnrs-gif.fr.
authors.forename: Sabine
authors.initials: S
authors.lastname: de la Porte
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001369:Axons / Q000187:drug effects*; D002087:Butyrates / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics; D004562:Electrocardiography; D007738:Kyphosis / Q000188:drug therapy* / Q000209:etiology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000187:drug effects / Q000235:genetics; D018482:Muscle, Skeletal / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000150:complications / Q000235:genetics / Q000473:pathology*; D012720:Severity of Illness Index; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014512:Ureohydrolases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002087:Butyrates; D016189:Dystrophin; D001120:Arginine; D014512:Ureohydrolases; C019944:creatinase; C033018:arginine butyrate
keywords: DMD; Dystrophin; Echocardiography; HDAC; Kyphosis; NO; QTrack; Utrophin; mdx