EFFECT OF INTRACELLULAR IRON LOADING ON LIPID-PEROXIDATION OF BRAIN-SLICES

The effect of artificially elevated cell iron content on oxygen-derive d free radical production was assessed in brain slices by use of an ir on ligand, 8-hydroxyquinoline (HQ). The iron complex Fe3+-HQ exhibited a high lipid solubility evidenced by n-octanol/water partition coeffi cient and was avidely taken up by brain slices. The catalytically acti ve 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 (TEARS) in brain homogenat es or slices exposed to two doses of Fe3+-HQ (10 mu M/20 mu M, 100 mu M/200 mu M) or Fe3+-citrate (10 mu M, 100 mu M). Addition of the iron complexes to homogenates or slices resulted in a dose-dependent increa se in lipid peroxidation. In homogenates, the effects were grossly sim ilar with both complexes, whereas in slices the effects of Fe-HQ were significantly higher than those of Fe-citrate. Lipid peroxidation pers isted in washed slices preexposed to Fe-HQ, but not in slices preexpos ed to the hydrophilic iron complex Fe-citrate. Fe-HQ-induced lipid per oxidation in slices was enhanced in the presence of H2O2, an effect th at was not seen using Fe-citrate. Addition of Fe-HQ to brain homogenat es 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.