Effect of intracellular iron loading on lipid peroxidation of brain slices.
The effect of artificially elevated cell iron content on oxygen-derived free radical production was assessed in brain slices by use of an iron ligand, 8-hydroxyquinoline (HQ). The iron complex Fe(3+)-HQ exhibited a high lipid solubility evidenced by n-octanol/water partition coefficient and was avidely taken up by brain slices. The catalytically active form of Fe3+ within the complex was evidenced by measuring the rate of ascorbate oxidation. Lipid peroxidation was assessed by measuring the thiobarbituric acid-reactive substances (TBARS) in brain homogenates or slices exposed to two doses of Fe(3+)-HQ (10 microM/20 microM, 100 microM/200 microM) or Fe(3+)-citrate (10 microM, 100 microM). Addition of the iron complexes to homogenates or slices resulted in a dose-dependent increase in lipid peroxidation. In homogenates, the effects were grossly similar with both complexes, whereas in slices the effects of Fe-HQ were significantly higher than those of Fe-citrate. Lipid peroxidation persisted in washed slices preexposed to Fe-HQ, but not in slices preexposed to the hydrophilic iron complex Fe-citrate. Fe-HQ-induced lipid peroxidation in slices was enhanced in the presence of H2O2, an effect that was not seen using Fe-citrate. Addition of Fe-HQ to brain homogenates in the presence of salicylic acid resulted in the production of 2,3-dihydroxybenzoic acid and the effect was potentiated in the presence of H2O2. This model of iron cell loading may be useful for evaluating the efficacy of antioxidant drugs.
Laboratoire de Pharmacodynamie, Faculté de Pharmacie, Université de Bourgogne, Dijon, France.
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Oubidar
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M
Boquillon
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Marie
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Bouvier
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Beley
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Bralet
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005290:Ferric Compounds / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation; D008055:Lipids; D008297:Male; D010084:Oxidation-Reduction; D015125:Oxyquinoline / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D005290:Ferric Compounds; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D017665:Hydroxyl Radical; D015125:Oxyquinoline; D006861:Hydrogen Peroxide; D007501:Iron; D001205:Ascorbic Acid