Antioxidant effects of LEDT in dystrophic muscle cells: involvement of PGC-1α and UCP-3 pathways.

Abstract

Reactive oxygen species and mitochondrial dysfunction play a crucial role in the pathophysiology of Duchenne muscular dystrophy (DMD). The light-emitting diode therapy (LEDT) showed beneficial effects on the dystrophic muscles. However, the mechanisms of this therapy influence the molecular pathways in the dystrophic muscles, particularly related to antioxidant effects, which still needs to be elucidated. The current study provides muscle cell-specific insights into the effect of LEDT, 48h post-irradiation, on oxidative stress and mitochondrial parameters in the dystrophic primary muscle cells in culture. Dystrophic primary muscle cells were submitted to LEDT, at multiple wavelengths (420nm, 470nm, 660nm and 850nm), 0.5J dose, and evaluated after 48h based on oxidative stress markers, antioxidant enzymatic system and biogenesis, and functional mitochondrial parameters. The mdx muscle cells treated with LEDT showed a significant reduction of H2O2 production and 4-HNE, catalase, SOD-2, and GR levels. Upregulation of UCP3 was observed with all wavelengths while upregulation of PGC-1α and a slight upregulation of electron transport chain complexes III and V was only observed following 850nm LEDT. In addition, the mitochondrial membrane potential and mitochondrial mass mostly tended to be increased following LEDT, while parameters like O2·- production tended to be decreased. The data shown here highlight the potential of LEDT as a therapeutic agent for DMD through its antioxidant action by modulating PGC-1α and UCP3 levels.