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.
Oubidar
M
M
Laboratoire de Pharmacodynamie, Faculté de Pharmacie, Université de Bourgogne, Dijon, France.
Boquillon
M
M
Marie
C
C
Bouvier
C
C
Beley
A
A
Bralet
J
J
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