ANTIOXIDANT EFFECTS OF 1,4-DIHYDROPYRIDINE AND NITROSO ARYL DERIVATIVES ON THE FE+3 ASCORBATE-STIMULATED LIPID-PEROXIDATION IN RAT-BRAIN SLICES/

1. Lipid peroxidation in rat brain slices was induced by Fe+3/ascorbat e. 2. Brain lipid peroxidation, as measured by malondialdehyde formati on, was inhibited by all the tested nitro aryl 1,4-dihydropyridine der ivatives over a wide range of concentrations. The time-course antioxid ant effects of the most representative agents were assessed. On the ba sis of both time-course and IC50 experiments the tentative order of an tioxidant activity on rat brain slices could be: nicardipine>nisoldipi ne>(R,S/S,R)-furnidipine> S)-furnidipine>nitrendipine>nimodipine>nifed ipine. 3. 1,4-Dihydropyridine derivatives that lack of a nitro group i n the molecule (isradipine, amlodipine) also inhibited lipid peroxidat ion in rat brain slices but at higher concentrations than that of nitr osubstituted derivatives. 4. All the tested nitroso aryl derivatives e thyl-4-(2-nitrosophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester (NTP), nitrosotoluene, nitrosobenzene] were more potent inhibitors of lipid peroxidation than were the parent nitro compounds. In conclusion , on the basis of the IC50 values determined, the rank order of antiox idant potency for these derivatives can be established as: ortho nitro sotoluene>NTP>nitrosobenzene. GEN PHARMAC 31;3:385-391, 1998. (C) 1998 Elsevier Science Inc.