The involvement of transition metal ions on iron-dependent lipid peroxidation

Abstract

The metals iron (Fe) and copper (Cu) are considered trace elements, and the metals cobalt (Co) and nickel (Ni) are known as ultra-trace elements, considering their presence in low to very low quantity in humans. The biologic activity of these transition metals is associated with the presence of unpaired electrons that favor their participation in redox reactions. They are part of important enzymes involved in vital biologic processes. However, these transition metals become toxic to cells when they reach elevated tissue concentrations and produce cellular oxidative damage. Phospholipid liposomes (0.5 mg/ml, phosphatidylcholine (PC)/phosphatidylserine (PS), 60/40) were incubated for 60 min at 37°C with 25 μM of Fe²⁺ in the absence and in the presence of Cu²⁺, Co²⁺, and Ni²⁺ (0–100 μM) with and without the addition of hydrogen peroxide (H₂O₂, 5–50 μM). Iron-dependent lipid peroxidation in PC/PS liposomes was assessed by thiobarbituric acid-reactive substances (TBARS) production. Metal transition ions promoted lipid peroxidation by H₂O₂ decomposition and direct homolysis of endogenous hydroperoxides. The Fe²⁺-H₂O₂-mediated lipid peroxidation takes place by a pseudo-second order process, and the Cu²⁺-mediated process by a pseudo-first order reaction. Co²⁺ and Ni²⁺ alone do not induce lipid peroxidation. Nevertheless, when they are combined with Fe²⁺, Fe²⁺-H₂O₂-mediated lipid peroxidation was stimulated in the presence of Ni²⁺ and was inhibited in the presence of Co²⁺. The understanding of the effects of transition metal ions on phospholipids is relevant to the prevention of oxidative damage in biologic systems.