Antioxidant, EUK-8, Prevents Murine Dilated Cardiomyopathy

Abstract

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 a 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.