Iron (III) Stimulation of Lipid Hydroperoxide-Dependent Lipid Peroxidation

Abstract

In an experimental system where both Fe2+ autoxidation and generation of reactive oxygen species is negligible, the effect of FeCl2 and FeCl3 on the peroxidation of phosphatidylcholine (PC) liposomes containing different amounts of lipid hydroperoxides (LOOH) was studied; Fe2+ oxidation, oxygen consumption and oxidation index of the liposomes were measured. No peroxidation was observed at variable FeCl2/FeCl3 ratio when PC liposomes deprived of LOOH by triphenylphosphine treatment were utilized. By contrast, LOOH containing liposomes were peroxidized by FeCl2. The FeCl2 concentration at which Fe2+ oxidation was maximal, defined as critical Fe2+ concentration [Fe2+]*, depended on the LOOH concentration and not on the amount of PC liposomes in the assay. The LOOH-dependent lipid peroxidation was stimulated by FeCl3 addition; the oxidized form of the metal increased the average length of radical chains, shifted to higher values the [Fe2+]* and shortened the latent period. The iron chelator KSCN exerted effects opposite to those exerted by FeCl3 addition. The experimental data obtained indicate the kinetics of LOOH-dependent lipid peroxidation depends on the Fe2+/Fe3+ ratio at each moment during the time course of lipid peroxidation. The results confirm that exogenously added FeCl3 does not affect the LOOH-independent but the LOOH-dependent lipid peroxidation; and suggest that the Fe3+ endogenously generated exerts a major role in the control of the LOOH-dependent lipid peroxidation.

Comparison of iron‐catalyzed DNA and lipid oxidation

“…The concentration-dependent effects of iron and hydrogen peroxide on lipid peroxidation in this system are consistent with and illustrate well the hypothesis that a 1:1 ratio of iron(II) to iron(III) is required, although this hypothesis has been challenged [12,16,17]. Low iron(II) concentrations stimulated lipid peroxidation, and this could have been due to reaction with preexisting lipid hydroperoxides to generate iron(III) in a 1:1 ratio with iron(II) [18,19]. In this case, inhibition by added hydrogen peroxide could be due to complete oxidation of iron(II).…”

The Role of Fe3+ on Fe2+-Dependent Lipid Peroxidation in Phospholipid Liposomes.

“…Recently, Tadolini et al have also reported 12,13) that Fe 3ϩ plays a major role in the control of LOOH-dependent lipid peroxidation. However, the present results showed that Fe 2ϩ -dependent TBARS production, regardless of the absence or presence of Fe 3ϩ , is almost independent of the LOOH level (1.45 to 0.28 nmol LOOH/mg phospholipid) in the liposomes (Table 2).…”

“…Recently, Tadolini et al have reported 12,13) that LOOH-dependent lipid peroxidation, not LOOH-independent, is dependent on the Fe 2ϩ /Fe 3ϩ ratio, and that Fe 3ϩ exerts a major influence on the control of the LOOH-dependent lipid peroxidation. These findings also strongly suggest that Fe 3ϩ is an important key factor in the initiation and/or progress of Fe 2ϩ -dependent lipid peroxidation, because membrane phospholipids generally contain small amounts of LOOH in the molecules.…”

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

“…37,38 Impaired mitochondrial oxidation has been considered to provide intracellular sources of oxidative stress in NASH/NAFLD. [4][5][6][7]31,39 We found enlarged mitochondria adjacent to oxPC-positive lipid droplets.…”