Effects of MCI-186 (edaravone), a novel free radical scavenger, upon experimental atherosclerosis in apolipoprotein E-deficient mice.
BACKGROUND
Recent evidence suggests that oxidative stress may play a role in the development of atherosclerosis. MCI-186 (3-methyl-1-phenyl-1-phyrazolin-5-one, edaravone) is a novel free radical scavenger, but it remains unclear whether free radical scavengers would be effective for the prevention of the disease.


RESULTS
Experimental atherosclerosis was induced in apolipoprotein E-deficient mice fed a high-fat diet containing 0.3% cholesterol. Mice were treated with an intraperitoneal injection of either MCI-186 1 mg/kg per day or MCI-186 10 mg/kg per day on alternate days over 4 weeks. Fatty streak lesion was suppressed by MCI-186 10 mg/kg per day administration, but not by mg/kg per day. Immunohistochemical analysis showed that macrophage and CD4+ T-cell accumulation and oxidative stress overload in the fatty streak lesion were suppressed in mice that received MCI-186 treatment.


CONCLUSIONS
MCI-186 administration suppressed the development of atherosclerosis, associated with reduced expression of both immune-activated cells and oxidative stress in fatty streak plaques.
Okabe
Taka-aki
TA
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Kishimoto
Chiharu
C
Shimada
Kana
K
Murayama
Toshinori
T
Yokode
Masayuki
M
Kita
Toru
T
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D013997:Time Factors
D001057:Apolipoproteins E; D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine