Efficacy of edaravone, a free radical scavenger, on left ventricular function and structure in diabetes mellitus.
This study was designed to assess the efficacy of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger that possesses anti-oxidant effects, on cardiac function and fine structure of the left ventricular myocardium in diabetes mellitus. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous development of type II diabetes (30 weeks; n = 15) were divided into two groups and treated with edaravone 30 mg/kg/d or vehicle for 2 weeks. OLETF rats showed hyperglycemia (352 +/- 71 mg/dl vs normal control; 128 +/- 52 mg/dl), increased thiobarbituric acid-reactive substances (TBARS; 6.9 +/- 2.5 nM/ml vs 2.8 +/- 0.6 nM/ml), and decreased superoxide dismutase activity (21.5 +/- 0.9 U/ml vs 25.8 +/- 0.7 U/ml). Increased left ventricular end-diastolic pressure (12 +/- 3 mm Hg vs 6 +/- 2 mm Hg) and hypertrophied cardiocytes (23.1 +/- 1.4 vs 17.6 +/- 1.0 microm) were also observed (P < 0.05, respectively). Edaravone could not improve plasma glucose level and hemodynamic parameters but significantly decreased TBARS values (3.8 +/- 0.5) and increased superoxide dismutase activity (24.5 +/- 0.8) (vs OLETF, P < 0.05, respectively). Moreover, edaravone effectively preserved cardiocyte diameter (18.2 +/- 0.9 microm) and the fine structure of mitochondria. Thus, edaravone exhibits modest cardiac protection in diabetes mellitus independent of blood sugar level.
Hayashi
Tetsuya
T
Third Department of Medicine, Osaka Medical College, Takatsuki, Japan. in3015@poh.osaka-med.ac.jp
Mori
Tatsuhiko
T
Sohmiya
Koichi
K
Okada
Yoshikatsu
Y
Inamoto
Sakiko
S
Okuda
Nobuaki
N
Mori
Hiroshi
H
Kitaura
Yasushi
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000097:blood / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008859:Microscopy, Polarization; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009249:NADP / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D020334:Rats, Inbred OLETF; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D000975:Antioxidants; D001786:Blood Glucose; D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; D009249:NADP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; D000077553:Edaravone; D000983:Antipyrine