The role of Fe3+ on Fe2+-dependent lipid peroxidation in phospholipid liposomes

Fe2+-dependent lipid peroxidation in phosphatidylcholine (PC) liposomes, assessed by thiobarbituric acid-reactive substances (TBARS) production, was stimulated in the presence of Fe3+ in a concentration-dependent manner. The rates of nitroblue tetrazolium (NBT) reduction and Fe2+ oxidation (Fe2+ disappearance and Fe3+ formation) were also enhanced by the addition of Fe3+ to the reaction mixture, and there is a good linear relationship between these parameters. These results suggest that the facilitation of reactive oxygen species (ROS) production via Fe2+ oxidation is closely related to the onset of the stimulatory effect of Fe3+ on Fe2+-dependent lipid peroxidation. On the other hand, results using the liposomes containing various concentrations of endogenous lipid hydroperoxides (LOOH) indicated that endogenous LOOH is not directly involved in the onset of the Fe3+ stimulatory effect on Fe2+-dependent TBARS production and ROS production. This hypothesis was further confirmed by the evidence that Fe2+-dependent ROS production and Fe2+ oxidation of dipalmitoylphosphatidylcholine liposomes were also stimulated by the addition of Fe3+. The results with several antioxidants and radical scavengers suggested that ROS related to Fe2+-dependent lipid peroxidation and its stimulation by Fe3+ are ferrous-oxygen complexes rather than superoxide anion, hydrogen peroxide and hydroxyl radicals. Based on these results, we proposed a possible mechanism for the onset of the Fe3+ stimulation in Fe2+-dependent lipid peroxidation.