ISSN:
1573-904X
Keywords:
lipid peroxides
;
ascorbic acid
;
vitamin E
;
felodipine
;
amlodipine
;
atherosclerosis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. The antioxidant activity of dihydropyridinecalcium channel antagonists was evaluated based on LDL oxidation kinetics,oxidative cell injury associated with reactive species generation, andincreases in free intracellular calcium (Ca2+) levels.Interactions with ascorbic acid were studied under conditions representativeof LDL oxidation in plasma and tissue. Methods. Analysis of antioxidant activity utilizedmeasurements of one-electron oxidation potentials and scavenging of peroxyradical-mediated oxidation. LDL antioxidant potency was determinedspectrophotometrically using copper-mediated oxidation kinetics in theabsence and presence of 100 μM ascorbic acid. Prevention ofoxidant-induced endothelial cell injury was determined from the formation ofreactive oxygen species generation and increases in intracellular freecalcium concentrations following addition of oxidized LDL or linoleic acidhydroperoxide. Results. Felodipine and amlodipine effectively inhibitperoxyl radical-mediated oxidation in lipoproteins and cells that ismarkedly enhanced in the presence of ascorbic acid. In the presence ofascorbic acid, inhibition of LDL oxidation is over four times greater thanin LDL treated without antioxidants, and oxidized LDL and linoleic acidhydroperoxide-induced reactive oxygen species formation is effectivelysuppressed in cells. Inhibition of intracellular calcium increases wasachieved using nM concentrations of felodipine or amlodipine. Conclusions. The additive effect for ascorbic acid and thecalcium channel antagonist is postulated to involve a combination ofperoxide-degrading and peroxyl radical scavenging reactions, demonstratingthe importance of lipid peroxides during LDL oxidation and oxidizedLDL-induced cytotoxicity. Cytoprotection is associated with inhibition ofoxidant-induced increases in intracellular free calcium. Both thecytoprotective and LDL antioxidant activity for these compounds ismanifested at concentrations approaching the therapeutic levels found inplasma.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007539607613
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