Antioxidant, EUK-8, prevents murine 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.


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.
Kawakami
Satoru
S
Department of Research and Development, Anti-Aging Science, Co Ltd, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Matsuda
Akina
A
Sunagawa
Tadahiro
T
Noda
Yoshihiro
Y
Kaneko
Takao
T
Tahara
Shoichi
S
Hiraumi
Yoshimi
Y
Adachi
Souichi
S
Matsui
Hiromitsu
H
Ando
Katsuyuki
K
Fujita
Toshiro
T
Maruyama
Naoki
N
Shirasawa
Takuji
T
Shimizu
Takahiko
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D005029:Ethylenediamines / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D018031:Connexin 43; D005029:Ethylenediamines; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II)