Análise da ação do canabidiol no modelo experimental de distrofia muscular de Duchenne

Abstract

Duchenne muscular dystrophy (DMD) is a serious genetic disorder, linked to the X chromosome, that causes progressive degeneration of skeletal muscles. Cannabidiol (CBD) exerts several beneficial effects, including anti-inflammatory and antioxidant properties. Given the potential beneficial action of CBD, in this study we verified the in vitro effect of full spectrum CBD oil on the viability of dystrophic muscle fiber and the in vivo effect on hepatoxicity, myonecrosis, inflammation and oxidative stress in the DMD model. For in vitro analysis, dystrophic cells from mdx mice were used, treated with full spectrum CBD and cell viability was assessed by MTT. In the in vivo analysis, two mouse strains were used, one being C57BL/10 (BL10) and the other mdx mouse strain, the latter divided into three groups, the first group being treated with saline (mdxSAL; n=7), the second group treated with grape seed oil (mdxOU; n=7) and the third group treated with full spectrum CBD oil (mdxCBD; n=7) 10mg/Kg for 14 days. After treatment, the biomarker Creatine kinase (CK) was analyzed in the blood, histomorphometry of hepatocytes and hepatic glycogen levels, in addition to the histopathology of the diaphragm (DIA) and quadriceps (QUA) muscles, analyzing myonecrotic fibers, inflammatory processes and the oxidative stress. In the in vitro study, full spectrum CBD oil produced a cytotoxic effect in a dose-dependent manner in the muscle cells of dystrophic mice. In the in vivo study, treatment with full spectrum CBD oil increased liver glycogen, producing improvements in the dystrophic phenotype of mdx mice. In the analysis of DIA and QUA muscles, treatment with full spectrum CBD oil prevented the myonecrosis process, reducing serum CK levels, the presence of central nuclei and positive IgG staining in dystrophic muscle tissue. It prevented inflammation, reducing the inflammatory area, the presence of macrophages and NF-κB levels. Furthermore, it prevented oxidative stress, increasing the antioxidant action of CAT and GSH molecules and prevented the onset and early exacerbation of oxidative stress even in the early stages of the disease, with a decrease in lipofuscin in the dystrophic muscle of mdx mice. Treatment with full spectrum CBD oil has been shown to be safe and effective in reducing the direct and indirect assessment parameters of DMD myopathy in the early stages of the disease. The results indicate that full spectrum CBD oil may represent a promising new approach to treating DMD.