Antioxidant, EUK-8, prevents murine dilated cardiomyopathy.

Satoru Kawakami, Akina Matsuda, Tadahiro Sunagawa, Yoshihiro Noda, Takao Kaneko, Shoichi Tahara, Yoshimi Hiraumi, Souichi Adachi, Hiromitsu Matsui, Katsuyuki Ando, Toshiro Fujita, Naoki Maruyama, Takuji Shirasawa, Takahiko Shimizu

Index: Circ. J. 73(11) , 2125-34, (2009)

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Abstract

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.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.EUK-8 treatment can prevent and cure murine DCM, so SOD/catalase mimetic treatment is proposed as a potential therapy for DCM.