title: Long-Term Therapy With Omega-3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice.
abstract: In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short-term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long-term therapy with omega-3 later in dystrophy progression. Three-month-old mdx mice received omega-3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long-term therapy with omega-3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF-α and NF-kB) in both muscles studied. The present study supports the long-term use of omega-3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials.
authors.affiliation: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
authors.forename: Leticia Montanholi
authors.initials: LM
authors.lastname: Apolinário
authors.affiliation: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
authors.forename: Samara Camaçari
authors.initials: SC
authors.lastname: De Carvalho
authors.affiliation: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
authors.forename: Humberto
authors.initials: H
authors.lastname: Santo Neto
authors.affiliation: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
authors.forename: Maria Julia
authors.initials: MJ
authors.lastname: Marques
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D018101:Mice, Inbred mdx; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017570:MyoD Protein / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012038:Regeneration / Q000187:drug effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: DMD; NF-kB; dystrophy; omega-3; quadriceps