From firstname.lastname@example.org@21:1/5 to All on Tue Dec 8 06:18:11 2015
Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy.
Das SK1,2, Wang W2,3, Zhabyeyev P1,2, Basu R1,2, McLean B2,3, Fan D2,3, Parajuli N1,2, DesAulniers J1,2, Patel VB1,2, Hajjar RJ4, Dyck JR5, Kassiri Z2,3, Oudit GY1,2.
Sci Rep. 2015 Dec 7;5:18132. doi: 10.1038/srep18132.
Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of
resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload
increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired
and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a
levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca(2+) homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were
suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-
overload cardiomyopathy at early and chronic stages of iron-overload.
Researchers now convincingly show that, via its iron-chelating effects, resveratrol is able to cross barriers that protect the brain from entry of toxins (blood/brain barrier) and reduce oxidation (spoilage) of fats and increase the activity of
protective antioxidant enzymes in the brain