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/ascorbate. 2. Brain lipid peroxidation, as measured by malondialdehyde formation, was inhibited by all the tested nitro aryl 1,4-dihydropyridine derivatives over a wide range of concentrations. The time-course antioxidant effects of the most representative agents were assessed. On the basis of both time-course and IC50 experiments the tentative order of antioxidant activity on rat brain slices could be: nicardipine>nisoldipine> (R,S/S,R)-furnidipine > (R,R/S,S)-furnidipine>nitrendipine>nimodipine> nifedipine. 3. 1,4-Dihydropyridine derivatives that lack of a nitro group in the molecule (isradipine, amlodipine) also inhibited lipid peroxidation in rat brain slices but at higher concentrations than that of nitro-substituted derivatives. 4. All the tested nitroso aryl derivatives [2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridinedicar. boxylic 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 antioxidant potency for these derivatives can be established as: ortho-nitrosotoluene>NTP>nitrosobenzene.
Laboratory of Pharmacology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
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Díaz-Araya
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Godoy
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Naranjo
J A
JA
Squella
M E
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Letelier
L J
LJ
Núñez-Vergara
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D015737:Nisoldipine / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000975:Antioxidants; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005290:Ferric Compounds; D009603:Nitroso Compounds; D015737:Nisoldipine; C038806:1,4-dihydropyridine; D001205:Ascorbic Acid; D010100:Oxygen