Effects of metal chelating agents on the oxidation of lipids induced by copper and iron.

The non-enzymatic oxidations of soybean phosphatidylcholine liposomes, methyl linoleate micelles and low-density lipoprotein in aqueous dispersions induced by copper and iron have been studied aiming specifically at elucidating the action of the metal chelating agents such as ethylenediaminetetraacetic acid disodium salt (EDTA), nitrilotriacetic acid (NTA), adenosine-5'-diphosphate disodium salt (ADP), desferrioxamine (DFO), penicillamine (PCM), and triethylene tetramine (TTM). The effects of chelators on chemiluminescence emitted from its probe luminol in the decomposition of tert-butyl hydroperoxide by metal ion were also studied. The effects of chelators on the oxidations depended both on the metal ion and the substrate. Namely, in the oxidations of both liposomes and micelles, EDTA and NTA suppressed the copper-induced oxidations, whereas they enhanced the oxidations induced by iron. ADP had little effect, while PCM and TTM had accelerating effect for both metal ions. On the other hand, in the oxidation of LDL, none of these chelators enhanced the oxidation. Especially, TTM and PCM suppressed the copper-induced oxidation of LDL, suggesting that the chelating agents blocked the access of the metal ion to the hydroperoxide within LDL. The effects of chelators on chemiluminescence emission were similar to those on the oxidations of liposomes and micelles. The cyclic voltammograms of metal complexes were also measured. The multiple effects of chelators on the rate of non-enzymatic, metal-catalyzed oxidations of lipids were interpreted by their influence on redox-potential and accessibility to hydroperoxide of the metal-chelator complex.