Antioxidant, EUK-8, prevents murine dilated cardiomyopathy

Area of Science:

• Cardiovascular Research
• Mitochondrial Medicine
• Oxidative Stress Biology

Background:

• Mice lacking manganese-superoxide dismutase (Mn-SOD) activity develop dilated cardiomyopathy (DCM).
• Oxidative stress and mitochondrial dysfunction are implicated in DCM pathogenesis.

Purpose of the Study:

• To investigate the therapeutic potential of the SOD/catalase mimetic EUK-8 in a mouse model of DCM.
• To assess the effects of EUK-8 on cardiac function, oxidative stress, and molecular defects in Mn-SOD deficient mice.

Main Methods:

• Presymptomatic and symptomatic heart/muscle-specific Mn-SOD-deficient (H/M-Sod2(-/-)) mice were treated with EUK-8 (30 mg/kg/day) for 4 weeks.
• Cardiac function, mitochondrial reactive oxygen species (ROS) production, oxidative damage, and connexin43 expression were evaluated.

Main Results:

• EUK-8 treatment suppressed cardiac dysfunction progression and diminished ROS production and oxidative damage in presymptomatic mice.
• EUK-8 effectively reversed cardiac dilatation and dysfunction in symptomatic H/M-Sod2(-/-) mice.
• EUK-8 treatment repaired a molecular defect in connexin43.

Conclusions:

• EUK-8 treatment can prevent and cure DCM in a murine model.
• SOD/catalase mimetic therapy, exemplified by EUK-8, is a promising therapeutic strategy for DCM.