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

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Autor(es):
da Silva, Heloina Nathallie Mariano ; Fernandes, Evelyn Mendes ; Pereira, Valeria Andrade ; Mizobuti, Daniela Sayuri ; Covatti, Caroline ; da Rocha, Guilherme Luiz ; Minatel, Elaine
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 19, n. 3, p. 23-pg., 2024-03-18.
Resumo

Purpose 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.Methods For the in vitro studies, the dystrophic primary muscle cells received 0.5J LEDT and 0.06 mu M IDE; and for the in vivo studies, the dystrophic quadriceps muscle received 3J LEDT and the mdx mice were treated with 200mg/kg IDE.Results LEDT and IDE treatment modulate autophagy by increasing autophagy markers (SQSTM1/p62, Beclin and Parkin) and signaling pathways (AMPK and TGF-beta). 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.Conclusion 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. (AU)

Processo FAPESP: 20/09733-4 - Efeito das terapias de fotobiomodulação e antioxidante sobre eventos celulares, teciduais, moleculares e bioquímicos nas fibras musculares distróficas de camundongos Mdx
Beneficiário:Elaine Minatel
Modalidade de apoio: Auxílio à Pesquisa - Regular