Ascorbic acid protects the diaphragm muscle against myonecrosis in mdx mice

Abstract Objective Oxidative stress contributes to myonecrosis in the dystrophin-deficient fibers of mdx mice and in Duchenne’s muscular dystrophy. We examined the effects of ascorbic acid (AA), an antioxidant and free radical scavenger, on the dystrophic diaphragm muscle. Methods Mdx mice (14 d old) received AA for 14 d. Control mdx mice received saline. The muscle damage was visualized by the penetration of Evans blue dye into myofibers and the extent of inflammation was assessed by histologic analysis. Creatine kinase levels were measured for the biochemical evaluation of muscle fiber degeneration. The levels of tumor necrosis factor-α (a proinflammatory cytokine) and 4-hydroxynonenal (a marker of lipid peroxidation) were analyzed by immunoblotting. Results Ascorbic acid decreased creatine kinase levels, myonecrosis, inflammation, and the levels of tumor necrosis factor-α and 4-hydroxynonenal. Conclusion The present results suggest that AA plays a protective role in dystrophic muscle degeneration, possibly by decreasing reactive oxygen species, and support further investigations of AA as a potential therapy for dystrophinopathies.