ANTIOXIDANT EFFECT OF CALCIUM-ANTAGONISTS ON MICROSOMAL-MEMBRANES ISOLATED FROM DIFFERENT BRAIN-AREAS

The antioxidant effect of Ca2+ antagonists on sheep brain microsomal membranes and on liposomes prepared with total lipids extracted from the membranes was studied. Microsomal membranes were isolated from three brain areas: frontal cortex, hippocampus and caudate nucleus. Lipid peroxidation was induced by ascorbic acid and measured by malondialdehyde formation. Seven Ca2+ antagonists representative of the major chemical classes (dihydropyridines, benzothiazepines, phenylalkylamines, alkylamines, diphenylpiperazines) were tested for their antioxidant activity over a wide range of concentrations (0-500-mu-M). The order of antioxidant activity on frontal cortex membrane phospholipids, expressed as 50% inhibition of peroxidation (antioxidant IC50), was: nifedipine (IC50 = 4-mu-M) > flunarizine (IC50 = 48-mu-M) > bepridil (IC50 = 50-mu-M) > verapamil (IC50 = 74-mu-M). The dihydropyridines, nitrendipine and nimodipine, and the benzothiazepine, diltiazem, did not affect peroxidation even at a concentration of 500-mu-M. Membrane phospholipids are the substrate for free radical-induced damage since the extent of peroxidation in brain microsomal membranes was equal to that produced in liposomes prepared from membrane lipids. Although the lipophilicity of certain Ca2+ channel antagonists can enhance their antioxidant activity, our data suggest that Ca2+ antagonists inhibit peroxidation of the membrane lipid bilayer by a free radical scavenger effect that may be related to their chemical structure.