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

doi:10.1253/circj.CJ-09-0204

Myocardial Disease

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

Author information

Satoru Kawakami
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology
Applied Biological Chemistry, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology
Department of Research and Development, Anti-Aging Science, Co Ltd
Akina Matsuda
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology
Applied Biological Chemistry, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology
Tadahiro Sunagawa
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology
Research Laboratories for Health & Gustatory Science, Asahi Breweries, Ltd
Yoshihiro Noda
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology
Takao Kaneko
Redox Regulation, Tokyo Metropolitan Institute of Gerontology
Shoichi Tahara
Redox Regulation, Tokyo Metropolitan Institute of Gerontology
Yoshimi Hiraumi
Department of Pediatrics, Kyoto University Hospital
Souichi Adachi
Department of Pediatrics, Kyoto University Hospital
Hiromitsu Matsui
Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo
Katsuyuki Ando
Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo
Toshiro Fujita
Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo
Naoki Maruyama
Aging Regulation, Tokyo Metropolitan Institute of Gerontology
Applied Biological Chemistry, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology
Takuji Shirasawa
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology
Department of Research and Development, Anti-Aging Science, Co Ltd
Department of Aging Control Medicine, Juntendo University Graduate School of Medicine
Takahiko Shimizu
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology
Applied Biological Chemistry, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology
Department of Research and Development, Anti-Aging Science, Co Ltd

Keywords: Connexin43 (Cx43), Dilated cardiomyopathy (DCM), EUK-8, Manganese-superoxide dismutase (Mn-SOD), Reactive oxygen species (ROS)

JOURNAL FREE ACCESS

2009 Volume 73 Issue 11 Pages 2125-2134

DOI https://doi.org/10.1253/circj.CJ-09-0204

View "Advance Publication" version (September 14, 2009).

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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. (Circ J 2009; 73: 2125-2134)

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