Inhibitory effects of a phosphate diester of alpha-tocopherol and ascorbic acid (EPC-K1) on myocardial infarction in rats.
The inhibitory effect of a phosphate diester of alpha-tocopherol and ascorbic acid (EPC-K1) was examined in myocardial infarction induced in rats, in comparison with a selective 5-lipoxygenase inhibitor, AA-861. EPC-K1 significantly reduced the infarct size at 24 and 48 h after ligation, whereas AA-861 reduced it only at 48 h after ligation. In in-vitro experiments, EPC-K1 inhibited not only superoxide anion generation (IC50 = 4.2 x 10(-5) M), but also acid phosphatase activity (IC50 = 2.4 x 10(-5) M) in rat polymorphonuclear leukocytes in a concentration-dependent manner, while AA-861 showed marginal effects on both actions. These results indicated that EPC-K1 induced cardioprotective effects by affecting neutrophil functions by inhibition of generation of superoxide-anion generation and acid-phosphatase activity. The mechanism of the reduction of the infarct size by EPC-K1 differed from that of AA-861, which latter inhibited 5-lipoxygenase and the formation of leukotriene B4.
Kuribayashi
Y
Y
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Katori
M
M
Majima
M
M
Yoshida
K
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D016227:Benzoquinones; D016166:Free Radical Scavengers; D016859:Lipoxygenase Inhibitors; D013481:Superoxides; D014810:Vitamin E; C066638:potassium ascorbyl tocopheryl phosphate; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D009195:Peroxidase; D001205:Ascorbic Acid