Antioxidant properties of EPC-K1: a study on mechanisms.
Scavenging effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8- tetramethyl-2-(4,8,12-trimethytridecyl)-2H-1-benzopyran- 6-yl-hydrogen phosphate] potassium salt (EPC-K1) on hydroxyl radicals, alkyl radicals and lipid radicals were studied with ESR spin trapping techniques. The inhibition effects of EPC-K1 on lipid peroxidation were assessed by TBA assay. The kinetics of EPC-K1 reacting with hydroxyl radicals and linoleic acid radicals were studied by pulse radiolysis. The active site of EPC-K1 and the structure-antioxidative activity relationships were discussed. The superoxide radicals scavenging capacity of the brain homogenate of EPC-K1-treated rats was measured. The results revealed that in comparison with Trolox and vitamin C, EPC-K1 showed better overall antioxidative capacity in vitro and in vivo. EPC-K1 was a moderate scavenger on hydroxyl radicals and alkyl radicals, a potent scavenger on lipid radicals, and an effective inhibitor on lipid peroxidation. EPC-K1 could react with hydroxyl radicals with a rate constant of 7.1 x 10(8) dm3 mol-1 s-1 and react with linoleic acid radicals with a rate constant of 2.8 x 10(6) dm3 mol-1 s-1. The active site of EPC-K1 was the enolic hydroxyl group. After administration of EPC-K1, the ability of rat brain to scavenge superoxide radicals was significantly increased. The potent scavenging effects of EPC-K1 on both hydrophilic and hydrophobic radicals were relevant with its molecular structure, which consisted of both hydrophilic and hydrophobic groups.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000737:chemistry; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D010545:Peroxides / Q000737:chemistry; D011675:Pulse Radiolysis; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology