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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
n-3 PUFAs, via their anti-inflammatory properties, could promote a systemic environment that improves satellite cell responsiveness to injury during aging by attenuating systemic inflammation, in a similar manner to nonsteroidal anti-inflammatory drugs (NSAIDs).
“n-3 PUFAs with their anti-inflammatory properties could promote a systemic environment that improves satellite cell responsiveness to injury during aging by attenuating systemic inflammation in a similar manner to nonsteroidal anti-inflammatory drugs (NSAIDs) [118,119,120].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [118]
Cites
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
Baldwin, A. S. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.649 · Cited by 5,882 · see citing works
NF-κB AND REL PROTEINS: Evolutionarily Conserved Mediators of Immune Responses
Ghosh, S., May, M. J., & Kopp, E. B. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.225 · Cited by 5,182 · see citing works
Cellular and Molecular Regulation of Muscle Regeneration
CHARGÉ, S. B. P., & Rudnicki, M. A. (2004) · Physiological Reviews · doi:10.1152/physrev.00019.2003 · Cited by 2,691 · see citing works
Inflammatory processes in muscle injury and repair.
Tidball, J. (2005) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00454.2004 · Cited by 1,392 · see citing works
Nuclear factor-?B: its role in health and disease
Kumar, A., Takada, Y., Boriek, A., & Aggarwal, B. (2004) · Journal of Molecular Medicine · doi:10.1007/s00109-004-0555-y · Cited by 933 · see citing works
The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy
Stedman, H. H., Sweeney, H. L., Shrager, J. B., Maguire, H., Panettieri, R., Petrof, B., Narusawa, M., Leferovich, J. M., Sladky, J. T., & Kelly, A. M. (1991) · Nature · doi:10.1038/352536a0 · Cited by 925 · see citing works
NF-κB-Induced Loss of MyoD Messenger RNA: Possible Role in Muscle Decay and Cachexia
D, D. C. G., Mayo, M. W., Madrid, L. V., Wang, C., & Baldwin, A. S. (2000) · Science · doi:10.1126/science.289.5488.2363 · Cited by 922 · see citing works
Vitamin E: Antioxidant Activity, Biokinetics, and Bioavailability
Burton, G. W., & Traber, M. G. (1990) · Annual Review of Nutrition · doi:10.1146/annurev.nu.10.070190.002041 · Cited by 760 · see citing works
MyoD is required for myogenic stem cell function in adult skeletal muscle
Megeney, L. A., Kablar, B., Garrett, K., Anderson, J. E., & Rudnicki, M. A. (1996) · Genes & Development · doi:10.1101/gad.10.10.1173 · Cited by 724 · see citing works
Manson, J. E., Bassuk, S. S., Lee, I.-M. M., Cook, N. R., Albert, M. A., Gordon, D., Zaharris, E., MacFadyen, J. G., Danielson, E., Lin, J., et al. (2011) · Contemporary Clinical Trials · doi:10.1016/j.cct.2011.09.009 · Cited by 552 · see citing works
Porter, J. D. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.3.263 · Cited by 442 · see citing works
Acharyya, S., Villalta, S. A., Bakkar, N., Bupha‐Intr, T., Janssen, P. M. L., Carathers, M., Li, Z.-W., Beg, A. A., Ghosh, S., Sahenk, Z., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30556 · Cited by 436 · see citing works
mdx mice show progressive weakness and muscle deterioration with age
Pastoret, C., & Sébille, A. (1995) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(94)00276-t · Cited by 402 · see citing works
Kumar, A., & Boriek, A. M. (2003) · The FASEB Journal · doi:10.1096/fj.02-0542com · Cited by 303 · see citing works
Bernasconi, P., TORCHIANA, E., Confalonieri, P. A., Brugnoni, R., Barresi, R., Mora, M., Cornelio, F., Morandi, L. O., & Mantegazza, R. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118101 · Cited by 297 · see citing works
MUSCLE DAMAGE IN MDX (DYSTROPHIC) MICE: ROLE OF CALCIUM AND REACTIVE OXYGEN SPECIES
Whitehead, N. P., Yeung, E. W., & Allen, D. G. (2006) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2006.04394.x · Cited by 294 · see citing works
Shinto, L., Quinn, J., Montine, T., Dodge, H. H., Woodward, W., Baldauf-Wagner, S., Waichunas, D., Bumgarner, L., Bourdette, D., Silbert, L., et al. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-130722 · Cited by 288 · see citing works
Baghdiguian, S., Martin, M., Richard, I., Pons, F., Astier, C., Bourg, N., Hay, R. T., Chemaly, R., Halaby, G., Loiselet, J., et al. (1999) · Nature Medicine · doi:10.1038/8385 · Cited by 277 · see citing works
Anti‐TNFα (Remicade®) therapy protects dystrophic skeletal muscle from necrosis
Grounds, M. D., & Torrisi, J. (2004) · The FASEB Journal · doi:10.1096/fj.03-1024com · Cited by 232 · see citing works
Thaloor, D., Miller, K. J., Gephart, J., Mitchell, P. O., & Pavlath, G. K. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.277.2.c320 · Cited by 213 · see citing works
Moon, D., Kim, K.-C., Jin, C., Han, M., Park, C., Lee, K., Park, Y., Choi, Y. H., & Kim, G. (2006) · International Immunopharmacology · doi:10.1016/j.intimp.2006.10.001 · Cited by 182 · see citing works
Activation of nuclear factor-κB in inflammatory myopathies and Duchenne muscular dystrophy
Monici, M. C., Aguennouz, M., Mazzeo, A. T., Messina, C., & Vita, G. (2003) · Neurology · doi:10.1212/01.wnl.0000049913.27181.51 · Cited by 177 · see citing works
Bushby, K. M. D., Francesco Muntoni, A., Urtizberea, A., Hughes, R. A., & Griggs, R. C. (2004) · Neuromuscular Disorders · doi:10.1016/j.nmd.2004.05.006 · Cited by 149 · see citing works
Messina, S., Bitto, A., Aguennouz, M., Minutoli, L., Monici, M. C., Altavilla, D., Squadrito, F., & Vita, G. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2005.11.021 · Cited by 147 · see citing works
Aziz, A., Liu, Q., & Dilworth, F. J. (2010) · Epigenetics · doi:10.4161/epi.5.8.13045 · Cited by 108 · see citing works
A reducing redox environment promotes C2C12 myogenesis: Implications for regeneration in aged muscle
Hansen, J. M., Klass, M., Harris, C., & CSETE, M. E. (2006) · Cell Biology International · doi:10.1016/j.cellbi.2006.11.027 · Cited by 100 · see citing works
Davidson, M. H. (2013) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000019 · Cited by 87 · see citing works
Gene and cell‐mediated therapies for muscular dystrophy
Konieczny, P., Swiderski, K., & Chamberlain, J. S. (2012) · Muscle & Nerve · doi:10.1002/mus.23738 · Cited by 80 · see citing works
Hindi, S. M., Shin, J., Ogura, Y., Li, H., & Kumar, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072121 · Cited by 69 · see citing works
Increased sphingosine-1-phosphate improves muscle regeneration in acutely injured mdx mice
Ieronimakis, N. M., Pantoja, M., Hays, A. L., Dosey, T. L., Qi, J., Fischer, K. A., Hoofnagle, A. N., Sadı́lek, M., Chamberlain, J. S., Ruohola‐Baker, H., et al. (2013) · Skeletal Muscle · doi:10.1186/2044-5040-3-20 · Cited by 57 · see citing works
Zgheel, F., Alhosin, M., Rashid, S. K., Burban, M., Auger, C., & Schini‐Kerth, V. B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105102 · Cited by 54 · see citing works
Shi, H., Boadu, E., Mercan, F., Le, A. M., Flach, R. J. R., Zhang, L., Tyner, K. J., Olwin, B. B., & Bennett, A. M. (2010) · The FASEB Journal · doi:10.1096/fj.09-150045 · Cited by 49 · see citing works
de Carvalho, S. C., Apolinário, L. M., Matheus, S. M. M., Neto, H. S., & Marques, M. J. (2013) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2013.09.007 · Cited by 48 · see citing works
Self-citationBouzianas, D. G., Bouziana, S. D., & Hatzitolios, A. I. (2013) · Nutrition Reviews · doi:10.1111/nure.12073 · Cited by 45 · see citing works
Matsumura, C. Y., de Oliveira, B. M., Durbeej, M., & Marques, M. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065831 · Cited by 45 · see citing works
Self-citationEffects of fish oil containing eicosapentaenoic acid and docosahexaenoic acid on dystrophic mdx mice
Maurício, A. F., Minatel, E., Neto, H. S., & Marques, M. J. (2012) · Clinical Nutrition · doi:10.1016/j.clnu.2012.11.013 · Cited by 39 · see citing works
Self-citationEicosapentaenoic acid decreases TNF-α and protects dystrophic muscles of mdx mice from degeneration
Machado, R. V., Maurício, A. F., Taniguti, A. P. T., Ferretti, R., Neto, H. S., & Marques, M. J. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.10.032 · Cited by 39 · see citing works
Self-citationMessina, S., Bitto, A., Aguennouz, M., Vita, G. L., Polito, F., Irrera, N., Altavilla, D., Marini, H., Migliorato, A., Squadrito, F., et al. (2011) · Neuromuscular Disorders · doi:10.1016/j.nmd.2011.04.014 · Cited by 33 · see citing works
An Omega-3 Fatty Acid-Enriched Diet Prevents Skeletal Muscle Lesions in a Hamster Model of Dystrophy
Fiaccavento, R., Carotenuto, F., Vecchini, A., Binaglia, L., Forte, G., Capucci, E., Maccari, A. M., Minieri, M., & Nardo, P. D. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100174 · Cited by 32 · see citing works
Tian, L., Cao, J., Deng, X., Zhang, C., Qian, T., Song, X., & Huang, B. (2014) · Genetics and Molecular Research · doi:10.4238/2014.february.28.13 · Cited by 11 · see citing works
Ferretti, R., Pertille, A., Neto, H. S., & Marques, M. J. (2011) · Muscle & Nerve · doi:10.1002/mus.22235 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Macrophages Are Key Regulators of Stem Cells during Skeletal Muscle Regeneration and Diseases
Dort, J., Fabre, P., Molina, T., & Dumont, N. A. (2019) · Stem Cells International · doi:10.1155/2019/4761427 · Cited by 182 · see citing works
Espino-González, E., Dalbram, E., Mounier, R., Gondin, J., Farup, J., Jessen, N., & Treebak, J. T. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.02.014 · Cited by 132 · see citing works
Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration
Tachtsis, B., Camera, D., & Lacham-Kaplan, O. (2018) · Nutrients · doi:10.3390/nu10030309 · Cited by 104 · see citing works
Jannas-Vela, S., Espinosa, A., Candia, A. A., Flores-Opazo, M., Peñailillo, L. E., & Valenzuela, R. (2023) · Nutrients · doi:10.3390/nu15040871 · Cited by 56 · see citing works
Stupin, M., Kibel, A., Stupin, A., Selthofer-Relatić, K., Matić, A., Mihalj, M., Mihaljević, Z., Jukić, I., & Drenjančević, I. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01129 · Cited by 59 · see citing works
Pohl, A., Schünemann, F., Bersiner, K., & Gehlert, S. (2021) · Nutrients · doi:10.3390/nu13113884 · Cited by 55 · see citing works
Skeletal Muscle Metabolism in Duchenne and Becker Muscular Dystrophy—Implications for Therapies
Heydemann, A. (2018) · Nutrients · doi:10.3390/nu10060796 · Cited by 43 · see citing works
Dalle, S., Roie, E. V., Hiroux, C., Vanmunster, M., Coudyzer, W., Suhr, F., Bogaerts, S., Thienen, R. V., & Koppo, K. (2020) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaa309 · Cited by 46 · see citing works
Rodríguez‐Cruz, M., Cruz‐Guzmán, O. D. R., Almeida‐Becerril, T., Solís-Serna, A. D., Atilano-Miguel, S., Sánchez-González, J. R., Barbosa-Cortés, L., Ruíz-Cruz, E. D., Huicochea, J. C., Cárdenas‐Conejo, A., et al. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.09.011 · Cited by 44 · see citing works
Moving towards successful exon-skipping therapy for Duchenne muscular dystrophy
Nakamura, A. (2017) · Journal of Human Genetics · doi:10.1038/jhg.2017.57 · Cited by 43 · see citing works
Potential role of omega-3 fatty acids on the myogenic program of satellite cells
Bhullar, A. S., Putman, C. T., & Mazurak, V. C. (2016) · Nutrition and Metabolic Insights · doi:10.4137/nmi.s27481 · Cited by 26 · see citing works
Wu, Z., Li, Y.-C., Zheng, Y., Zhou, M., Li, H. Z., Wu, S.-X., Zhao, X., Yang, Y., & Du, L. (2024) · Food & Function · doi:10.1039/d4fo04341c · Cited by 20 · see citing works
de Carvalho, S. C., Matsumura, C. Y., Neto, H. S., & Marques, M. J. (2017) · Cytokine · doi:10.1016/j.cyto.2017.12.006 · Cited by 17 · see citing works
Self-citationMild Aerobic Exercise Training Hardly Affects the Diaphragm of mdx Mice
Morici, G., Frinchi, M., Pitruzzella, A., Liberto, V. D., Barone, R., Pace, A., Felice, V. D., Belluardo, N., Cappello, F., Mudò, G., et al. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25573 · Cited by 16 · see citing works
de Carvalho, S. C., Hindi, S. M., Kumar, A., & Marques, M. J. (2017) · Cell and Tissue Research · doi:10.1007/s00441-017-2640-x · Cited by 15 · see citing works
Self-citationBenefits and pathologies associated with the inflammatory response
Singh, P., & Chazaud, B. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112905 · Cited by 13 · see citing works
Cho, H. J., Ahn, S. H., Lee, Y., Lee, S. H., Im, D., Kim, I., Koh, J., Kim, S., & Kim, B. (2017) · Calcified Tissue International · doi:10.1007/s00223-017-0323-y · Cited by 10 · see citing works
Villaldama-Soriano, M. A., Rodríguez‐Cruz, M., la Cruz, S. Y. H.-D., Almeida‐Becerril, T., Cárdenas‐Conejo, A., & Baeza, C. W. (2021) · European Journal of Neurology · doi:10.1111/ene.15184 · Cited by 9 · see citing works
Ferreira, L. L., Gomes, F. S., Nascimento, B. G., Corsini, W., dos Reis, L. F. C., Oliveira‐Silva, J. M., da Silva, J. R. T., da Silva, M. L., Castro‐Gamero, A. M., & Hermes, T. D. A. (2025) · Muscle & Nerve · doi:10.1002/mus.28337 · Cited by 3 · see citing works
Versari, I., Bavelloni, A., Traversari, M., Burattini, S., Battistelli, M., Gobbi, P., Faenza, I., & Salucci, S. (2025) · Nutrients · doi:10.3390/nu17061039 · Cited by 3 · see citing works
Vari, F., Bisconti, E., Serra, I., Stanca, E., Friuli, M., Vergara, D., & Giudetti, A. (2025) · Biomedicines · doi:10.3390/biomedicines13071568 · Cited by 3 · see citing works
Wang, F., Wen, J., Zhang, G., Liu, Z., Zhong, H., Zhang, G., Sun, Y., Yu, P., Wang, Y., & Zhang, Z. (2020) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2020.88006
- Authors
- Apolinário, L. M., De Carvalho, S. C., Santo Neto, H., & Marques, M. J.
- Affiliations
- Departamento de Biologia Estrutural e Funcional Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP Campinas SP Brazil
- Venue
- The Anatomical Record
- Publisher
- Wiley
- Published
- 2015-06-22
- Volume
- 298
- Issue
- 9
- Pages
- 1589-1596
- ISSN
- 1932-8486 (ISSN-L)
- 1932-8494
- OpenAlex
- W1894937150
- Cited by
- 22
- References
- 41
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 2
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Anatomical Record (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion)
- Americanae (AECID Library) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (08/58491-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- omega-3 fatty acids, eicosapentaenoic acid, Duchenne muscular dystrophy, mdx mice, muscle necrosis, skeletal muscle regeneration, MyoD, inflammation, TNF-α, NF-κB, long-term dietary supplementation, diaphragm, quadriceps
- MeSH terms
- Animals, Diaphragm, Disease Models, Animal, Docosahexaenoic Acids, Drug Administration Schedule, Female, Male, Muscular Dystrophy, Animal, Necrosis, Regeneration, Time Factors, Tumor Necrosis Factor-alpha, Eicosapentaenoic Acid, NF-kappa B, MyoD Protein, Mice, Inbred mdx, Inflammation Mediators, Muscular Dystrophy, Duchenne, Quadriceps Muscle
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
