Terapia de fotobiomodulação em modelo experimental de distrofia muscular de Duchenne: uma nova alternativa terapêutica

Abstract

The first study aimed to analyze the protective effects of photobiomodulation therapy (PBMT) on skeletal muscle tissue to delay dystrophy progression in mdx mice. To this aim, mice were randomly divided into 5 different experimental groups: Wild Type (WT), Placebo-control (DMDmdx), PBMT with doses of 1J, 3J and 10J. For second study aimed to analyze and compare effects of photobiomodulation therapy, non-steroidal anti-inflammatory drug (NSAID) and glucocorticoid as isolated or combined treatments on dystrophin, skeletal muscle tissue morphology, and functional performance in mdx mice. For such, mice were randomly divided into 7 different experimental groups: Wild Type (WT), Placebo-control, Prednisone, NSAID, PBMT, PBMT + Prednisone, and PBMT + NSAID. Prednisone treatment (glucocorticoid) was administered to animals daily as NSAID treatment with ibuprofen. PBMT was applied 3 times a week with direct contact at skin on animals’ hindlimbs in a single point (tibialis anterior muscle – bilaterally). For combined treatments each modality was applied as described previously. All treatments were performed during 14 weeks, and started with animals at 6 weeks of age. It was analyzed muscle morphology, dystrophin trough immunohistochemistry, and functional performance. Results first study: PBMT with a 10J dose significantly improved (p<0.001) functional performance compared to all other experimental groups. Muscle morphology was improved by all PBMT doses, with better outcomes with the 3J and 10J doses. Gene expression of dystrophin was significantly increased with 3J (p<0.01) and 10J (p<0.01) doses when compared to placebo- control group. Regarding protein expression of dystrophin, 3J (p<0.001) and 10J (p<0.05) doses also significantly showed increase compared to placebo- control group. Results second study: Both Prednisone (p<0.01), PBMT (p<0.001), PBMT + Prednisone (p<0.01), and PBMT + NSAID (p<0.01) treatments increased dystrophin compared to placebo-control group. Prednisone, PBMT, and PBMT + Prednisone also lead to improvement in morphological aspects of skeletal muscle tissue in a similar way. However, only Prednisone (p<0.05) and PBMT (p<0.0001) treatments lead to improved muscular function in mice compared to placebo-control group (p<0.05). Interestingly, PBMT treatment presented best outcomes for functional

performance compared to all other groups (p<0.0001). We conclude that PBMT can preserve muscle morphology and improve muscular function of mdx mice through modulation of dystrophin, and presents better outcomes than Prednisone. Since PBMT is a non-pharmacological treatment that doesn’t present side effects and it’s easy handling, PBMT raises as a very promising tool to decrease detrimental changes of Duchenne Muscular Dystrophy in skeletal muscles, becoming a very interesting alternative to pharmacological treatment.