In vitro antioxidant activity of calcium antagonists against LDL oxidation compared with alpha-tocopherol.
The dose-dependent (1, 5, 10, 50 microM) antioxidative activity of calcium antagonists (verapamil, diltiazem, nifedipine, amlodipine, isradipine or lacidipine) and alpha-tocopherol against copper-induced LDL (0.25 mg/ml) oxidation was compared by measuring the diene formation and the content of TBARS. For diltiazem no antioxidant effect could be found, whereas the other calcium antagonists and alpha-tocopherol have demonstrated antioxidant activity at least at concentrations of 10 and 50 microM: alpha-tocopherol > lacidipine > nifedipine > isradipine, verapamil, amlodipine. Additionally, alpha-tocopherol and lacidipine were able to attenuate LDL-oxidation significantly at 1 and 5 microM. These results indicate in vitro antioxidative activity of calcium antagonists especially from the dihydropyridine-type with greatest activity for the strongly lipophilic lacidipine. This might be one possible antiatherogenic mechanism of calcium antagonists, since oxidative modification enhances the atherogenic potential of LDL.
Lupo
E
E
University Hospital of Zürich, Switzerland.
Locher
R
R
Weisser
B
B
Vetter
W
W
D000328:Adult; D017311:Amlodipine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017275:Isradipine / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D012016:Reference Values; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014700:Verapamil / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D017311:Amlodipine; C060285:lacidipine; D003300:Copper; D014700:Verapamil; D004110:Diltiazem; D017275:Isradipine