Antioxidant, EUK-8, Prevents Murine Dilated Cardiomyopathy

Background: Mice lacking manganese-superoxide dismutase (Mn-SOD) activity exhibit the typical pathology of dilated cardiomyopathy (DCM) In the present Study. presymptomatic and symptomatic mutant mice were treated with the SOD/catalase mimetic, EUK-8 Methods and Results: Presymptomatic heart/muscle-specific Mn-SOD-deficient mice (H/M-Sod2(-/-)) were treated with EUK-8 (30 mg kg(-1) . day(-1)) for 4 weeks. and then cardiac function and the reactive oxygen species (ROS) production in their heart mitochondria were assessed. EUK-8 treatment Suppressed the progression of cardiac dysfunction and diminished ROS production and oxidative damage. Furthermore, EUK-8 treatment effectively reversed the cardiac dilatation and dysfunction observed in symptomatic H/M-Sod2(-/-) mice. Interestingly, EUK-8 treatment repaired it molecular defect in connexin43 Conclusions: EUK-8 treatment can prevent and cure murine DCM. so SOD/catalase mimetic treatment is proposed as a potential therapy for DCM. (Circ J 2009; 73: 2125-2134)