LEDT and Idebenone treatment modulate autophagy and improve regenerative capacity in the dystrophic muscle through an AMPK-pathway

Considering the difficulties and challenges in Duchenne muscular dystrophy (DMD) treatment, such as the adverse effects of glucocorticoids, which are the main medical prescription used by dystrophic patients, new treatment concepts for dystrophic therapy are very necessary. Thus, in this study, we e...

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Published in:	PloS one Vol. 19; no. 3; p. e0300006
Main Authors:	Silva, Heloina Nathalliê Mariano da, Fernandes, Evelyn Mendes, Pereira, Valéria Andrade, Mizobuti, Daniela Sayuri, Covatti, Caroline, Rocha, Guilherme Luiz da, Minatel, Elaine
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 18-03-2024 Public Library of Science (PLoS)
Subjects:	AMP-Activated Protein Kinases - metabolism Animals Antioxidants Autophagy Biology and Life Sciences Care and treatment Corticosteroids Diagnosis Disease Models, Animal Duchenne muscular dystrophy Health aspects Humans Medicine and Health Sciences Mice Mice, Inbred mdx Muscle, Skeletal - metabolism Muscular Dystrophy, Duchenne - drug therapy Muscular Dystrophy, Duchenne - metabolism Physical Sciences Research and Analysis Methods Transforming growth factors Ubiquinone - analogs & derivatives Brazil
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Summary:	Considering the difficulties and challenges in Duchenne muscular dystrophy (DMD) treatment, such as the adverse effects of glucocorticoids, which are the main medical prescription used by dystrophic patients, new treatment concepts for dystrophic therapy are very necessary. Thus, in this study, we explore the effects of photobiomodulation (PBM; a non-invasive therapy) and Idebenone (IDE) treatment (a potent antioxidant), applied alone or in association, in dystrophic muscle cells and the quadriceps muscle, with special focus on autophagy and regenerative pathways. For the in vitro studies, the dystrophic primary muscle cells received 0.5J LEDT and 0.06μM IDE; and for the in vivo studies, the dystrophic quadriceps muscle received 3J LEDT and the mdx mice were treated with 200mg/kg IDE. LEDT and IDE treatment modulate autophagy by increasing autophagy markers (SQSTM1/p62, Beclin and Parkin) and signaling pathways (AMPK and TGF-β). Concomitantly, the treatments prevented muscle degeneration by reducing the number of IgG-positive fibers and the fibers with a central nucleus; decreasing the fibrotic area; up-regulating the myogenin and MCH-slow levels; and down-regulating the MyoD and MHC-fast levels. These results suggest that LEDT and IDE treatments enhance autophagy and prevented muscle degeneration in the dystrophic muscle of the experimental model. These findings illustrate the potential efficacy of LEDT and IDE treatment as an alternative therapy focused on muscle recovery in the dystrophic patient.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0300006