Evidence That Free Fatty Acid-Iron Complexes Directly Initiate Lipid Peroxidation in Vitro and in Vivo: A New Mechanism of Oxidative Stress

Through a series of biochemical and histochemical experiments we explored the novel hypothesis that iron and free fatty acids, liberated after tissue injury, combine to form liposoluble complexes that directly initiate lipid peroxidation. The addition of 100 M ferric iron to 30 mM linoleate suspensions at pH 7.4 produced time dependent lipid peroxidation, measured as conjugated diene formation. Complexes of 100 M ferric iron and 600 M pentanoate also initiated formation of conjugated dienes in linoleate suspensions and formation of malondialdehyde-like materials in rat liver slices. A histochemical stain for free fatty acids revealed positive reactions within cell membranes in traumatized regions of rat liver tissue that underwent compression injury followed by thirty minutes of blood perfusion, but not in nontraumatized control regions. The diaminobenzidine-H2O2 histochemical reaction for iron, revealed increased levels of redox cyclable iron in the membranes and the cytoplasm of traumatized hepatocytes. We propose that traumatic injury initiates cascades leading to liberation of iron from storage proteins and free fatty acids from membranes, which combine, distribute to the lipid domains of cell membranes, and directly initiate lipid peroxidation