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 months) of the disease. Research Methods and Procedures Mdx mice (8 months old) received omega-3 oil (commercially available fish oil; FDC Vitamins; Omega-3), for 5 months. Untreated- mdx mice received mineral oil. Heart and diaphragm (DIA) muscle were evaluated by morphometric (fibrosis), molecular (western blot, inflammatory markers), biochemical (creatine kinase) and functional (electrocardiogram, ECG) 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 months of age (untreated- mdx : 20.8 % of fibrosis; omega-3-treated: 15.7 % of fibrosis in right ventricle). Omega-3 improved some ECG parameters. Markers of inflammation (tumor necrosis factor alpha, TNF-α; matrix metalloprotease (MMP)-9, and their tissue inhibitor TIMP-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 pro-fibrotic transforming growth factor beta (TGF-β). Omega-3 ameliorated the dystrophic DIA in almost all of the parameters evaluated (fibrosis, TGF-β, MMP-9, and TIMP-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.