Apple Polyphenols Regulate Mitochondrial Superoxide Generation and Extend Survival in a Mouse Model of Dilated Cardiomyopathy

Apple polyphenols (AP), which contain procyanidins as major components, have been reported to display potent antioxidant activity and several beneficial health effects. To investigate the protective effect of AP intake against murine cardiomyopathy caused by endogenous oxidative stress, we orally administered AP to heart/muscle-specific manganese- superoxide dismutase (Mn-SOD)-deficient (H/M-Sod2 -/- ) mice (Nojiri et al., 2006). Dietary AP significantly increased the survival of the mutant mice, extending their mean lifespan by 29%. Dietary AP also suppressed the progression of cardiac dilatation and fibrosis in the H/M-Sod2 -/- mice. In vitro experiments revealed that AP treatment strongly suppressed the production of hydrogen peroxide induced reactive oxygen species (ROS) in C2C12 myoblast cells and endogenous superoxide production in Mn-SOD-deficient cells. Furthermore, dietary AP suppressed ROS production in Mn- SOD-deficient cardiomyocytes and oxidative DNA damage in vivo. These results indicate that dietary AP improved the survival and pathology of short-lived mice with cardiomyopathy by suppressing mitochondrial superoxide production.