Effects of fish oil containing eicosapentaenoic acid and docosahexaenoic acid on dystrophic mdx mice hearts at later stages of dystrophy

Author(s)

Mauricio, Adriana Fogagnolo ^[1] ; Pereira, Juliano Alves ^[1] ; Neto, Humberto Santo ^[1] ; Marques, Maria Julia ^[1]

Affiliation

^[1] Univ Campinas Unicamp, Inst Biol, Dept Struct & Funct Biol, Sao Paulo - Brazil

• Document type: Journal article
• Source: NUTRITION; v. 32, n. 7-8, p. 855-862, JUL-AUG 2016.
• Web of Science Citations: 5

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 x 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 beta-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. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/13577-1 - Biomarkers of cardiomyopathy in dystrophy: a metabolomic study and pharmacological therapy
• Grantee: Adriana Fogagnolo Mauricio
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/04782-6 - Pre-clinical studies in the mdx mouse: metabolomics, biomarkers and omega-3 therapy
• Grantee: Maria Julia Marques
• Support Opportunities: Regular Research Grants