title: Effects of fish oil containing eicosapentaenoic acid and docosahexaenoic acid on dystrophic mdx mice hearts at later stages of dystrophy.
abstract: OBJECTIVE
  In the present study, we investigated whether omega-3 would be effective against dystrophic cardiomyopathy at later stages (13 and 17 mo) of the disease.
  
  
  METHODS
  Mdx mice (8 mo old) received omega-3 oil (commercially available fish oil; FDC vitamins; omega-3) for 5 mo. Untreated-mdx mice received mineral oil. Heart and diaphragm muscle were evaluated by morphometric (fibrosis), molecular (western blot, inflammatory markers), biochemical (creatine kinase), and functional (electrocardiogram) analyses.
  
  
  RESULTS
  Mdx mice presented elevated plasma levels of cardiac creatine kinase (41.2 U/L in normal × 119.6 U/L in untreated-mdx mice), which were significantly decreased by omega-3 treatment. Heart fibrosis was significantly ameliorated by omega-3 treatment at 17 mo of age (untreated-mdx: 20.8% of fibrosis; omega-3-treated: 15.7% of fibrosis in right ventricle). Omega-3 improved some electrocardiogram parameters. Markers of inflammation (tumor necrosis factor alpha, matrix metalloprotease-9, and tissue inhibitor of metalloprotease 1) in mdx heart were significantly decreased by omega-3 treatment. Omega-3 increased β-dystroglycan levels in mdx heart and did not affect the levels of the profibrotic transforming growth factor beta. Omega-3 ameliorated the dystrophic diaphragm in almost all of the parameters evaluated (fibrosis, transforming growth factor beta, metalloprotease-9, and tissue inhibitor of metalloprotease 1).
  
  
  CONCLUSIONS
  The present study suggests that omega-3 may be useful in ameliorating dystrophic cardiomyopathy and diaphragm dystrophy in mdx mice at later stages of the disease, further supporting the use of omega-3 in DMD clinical trials.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Fogagnolo Mauricio
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Juliano Alves
authors.initials: JA
authors.lastname: Pereira
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Humberto
authors.initials: H
authors.lastname: Santo Neto
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. Electronic address: marques@unicamp.br.
authors.forename: Maria Julia
authors.initials: MJ
authors.lastname: Marques
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D005395:Fish Oils; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: Cardiomyopathy; DMD; Heart; MMP-9; Omega-3; TGF-β