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: Leticia Montanholi Apolinário, Samara Camaçari De Carvalho, Humberto Santo Neto, Maria Julia Marques
• Journal: Anatomical record (Hoboken, N.J. : 2007) (Anat Rec (Hoboken)) Vol. 298 Issue 9 Pg. 1589-96 (Sep 2015) ISSN: 1932-8494 [Electronic] United States
• PMID: 26011009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Inflammation Mediators
• MyoD Protein
• MyoD1 myogenic differentiation protein
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Docosahexaenoic Acids
• Eicosapentaenoic Acid

Topics

• Animals
• Diaphragm (drug effects, metabolism, pathology, physiopathology)
• Disease Models, Animal
• Docosahexaenoic Acids (administration & dosage)
• Drug Administration Schedule
• Eicosapentaenoic Acid (administration & dosage)
• Female
• Inflammation Mediators (metabolism)
• Male
• Mice, Inbred mdx
• Muscular Dystrophy, Animal (drug therapy, metabolism, pathology, physiopathology)
• Muscular Dystrophy, Duchenne (drug therapy, metabolism, pathology, physiopathology)
• MyoD Protein (metabolism)
• NF-kappa B (metabolism)
• Necrosis
• Quadriceps Muscle (drug effects, metabolism, pathology, physiopathology)
• Regeneration (drug effects)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)