Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species

Abstract

Duchenne muscular dystrophy is a severe X-linked congenital disorder characterized by lethal muscle wasting caused by the absence of the structural protein dystrophin. Because generation of reactive oxygen species appears to play an important role in the pathogenesis of this disease, we tested whether antioxidant green tea extract could diminish muscle necrosis in the mdx mouse dystrophy model. A diet supplemented with 0.01% or 0.05% green tea extract was fed to dams and neonates for 4 wk beginning on the day of birth. Muscle necrosis and regeneration were determined in stained cryosections of soleus and elongator digitorum longus muscles. Radical scavenging by green tea extract was determined in differentiated cultured C2C12 cells treated with tert-butylhydroperoxide, with the use of 2',7'-dichlorofluorescin diacetate as a radical detector. This feeding regimen significantly and dose-dependently reduced necrosis in the fast-twitch muscle elongator digitorum longus but at the doses tested had no effect on the slow-twitch soleus muscle. Green tea extract concentration-dependently decreased oxidative stress induced by tert-butylhydroperoxide treatment of cultured mouse C2C12 myotubes. The lower effective dose tested in mdx mice corresponds to approximately equal to 1.4 L (7 cups) green tea/d in humans. Green tea extract may improve muscle health by reducing or delaying necrosis in mdx mice by an antioxidant mechanism.