Duchenne muscular dystrophy progression induced by downhill running is accompanied by increased endomysial fibrosis and oxidative damage DNA in muscle of mdx mice

This study aims to understand the relationship between myogenic regulation, inflammation and oxidative stress parameters, and disease progression induced by downhill running in the skeletal muscle of an experimental model of DMD. Six-month-old C57BL/10 and C57BL/10-DMDmdx male mice were distributed into three groups: Control (C),mdx, andmdx + Exercise (mdx + Ex). Animals were trained in a downhill running protocol for seven weeks. The gastrocnemius muscle was subjected to histopathology, muscle regeneration (myoD and myogenin), inflammation (COX-2), oxidative stress (8-OHdG) immunohistochemistry markers, and gene expression (qPCR) of NF-kB and NA DP(H)Oxidase 2 (NOX-2) analysis. In themdx + Ex group, the gastrocnemius muscle showed a higher incidence of endomysial fibrosis and a lower myonecrosis percentage area. Immunohistochemical analysis revealed decreased myogenin immunoexpression in themdx group, as well as accentuated immunoexpression of nuclear 8-OHdG in bothmdx groups and increase in cytoplasmic 8-OHdG only in themdx + Ex. COX-2 immunoexpression was related to areas of regeneration process and inflammatory infiltrate in themdx group, while associated with areas of muscle fibrosis in themdx + Ex. Moreover, the NF-kB gene expression was not influenced by exercise; however, a NAD(P)HOxidase 2 increase was observed. Oxidative stress and oxidative DNA damage play a significant role in the DMD phenotype progression induced by exercise, compromising cell...
Source: Journal of Molecular Histology - Category: Laboratory Medicine Source Type: research