A marked stimulation of Fe 3+-dependent lipid peroxidation in phospholipid liposomes under acidic conditions

Abstract

Lipid peroxidation in phosphatidylcholine liposomes induced by Fe 3+ alone, assessed by thiobarbituric acid-reactive substances (TBARS) production, was markedly enhanced as the solution pH was lowered from 7.4 to 5.5. On the other hand, at physiological pH, TBARS production by Fe 3+ was almost negligible. Results of the radical scavenger experiments with superoxide dismutase, catalase and hydroxyl radical ( OH) scavengers (sodium benzoate, mannitol and dimethylthiourea), deoxyribose degradation and ESR spectrometry suggest that the stimulation of Fe 3+-dependent lipid peroxidation under acidic conditions is involved in generation of superoxide anion (O 2 − ), hydrogen peroxide (H 2O 2) and OH during the reaction. The stimulation of Fe 3+-dependent TBARS production by increasing the [H +] completely disappeared by triphenylphosphine (TPP) treatment of the liposomes, but the reaction was reversible with either incorporation of cumen hydroperoxide (CumOOH) into the TPP-treated liposomes or the addition of CumOOH to the treated liposomes. Incubation of the CumOOH-incorporated TPP-treated liposomes with Fe 3+ at pH 5.5 also resulted in OH generation. Based on these results, a possible mechanism of stimulatory effect of Fe 3+ on lipid peroxidation under acidic conditions is discussed.