Key result
EUK-8 reverses established cardiac dilatation and pump failure while suppressing ROS in murine DCM.
Why the study?
Mice lacking manganese-superoxide dismutase (Mn-SOD) activity develop dilated cardiomyopathy, and the potential therapeutic effect of the SOD/catalase mimetic EUK-8 was investigated.
EUK-8 may attenuate cardiomyopathy in Mn-SOD-deficient mice; leaves open translation to human 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 x 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.
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Kawakami et al. (2009) studied Dilated Cardiomyopathy. EUK-8 vs. Saline was evaluated on Cardiac dysfunction (echocardiographic parameters including LVIDd, LVIDs, %FS) and reactive oxygen species production (p=<0.05). EUK-8 treatment suppressed the progression of cardiac dysfunction, diminished ROS production, and effectively reversed established cardiac dilatation and pump failure in a murine model of dilated cardiomyopathy.
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