The involvement of iron in lipid peroxidation. Importance of ferric to ferrous ratios in initiation.
Intense lipid peroxidation of brain synaptosomes initiated with Fenton's reagent (H2O2 + Fe2+) began instantly upon addition of Fe2+ and preceded detectable OH. formation. Although mannitol or Tris partially blocked peroxidation, concentrations required were 10(3)-fold in excess of OH. actually formed, and inhibition by Tris was pH dependent. Lipid peroxidation also was initiated by either Fe2+ or Fe3+ alone, although significant lag phases (minutes) and slowed reaction rates were observed. Lag phases were dramatically reduced or nearly eliminated, and reaction rates were increased by a combination of Fe3+ and Fe2+. In this instance, lipid peroxidation initiated by optimal concentrations of H2O2 and Fe2+ could be mimicked or even surpassed by providing optimal ratios of Fe3+ to Fe2+. Peroxidation observed with Fe3+ alone was dependent upon trace amounts of contaminating Fe2+ in Fe3+ preparations. Optimal ratios of Fe3+:Fe2+ for the rapid initiation of lipid peroxidation were on order of 1:1 to 7:1. No OH. formation could be detected with this system. Although low concentrations of H2O2 or ascorbate increased lipid peroxidation by Fe2+ or Fe3+, respectively, high concentrations of H2O2 or ascorbate (in excess of iron) inhibited lipid peroxidation due to oxidative or reductive maintenance of iron exclusively in Fe2+ or Fe3+ form. Stimulation of lipid peroxidation by low concentrations of H2O2 or ascorbate was due to the oxidative or reductive creation of Fe3+:Fe2+ ratios. The data suggest that the absolute ratio of Fe3+ to Fe2+ was the primary determining factor for the initiation of lipid peroxidation reactions.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005290:Ferric Compounds / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013574:Synaptosomes / Q000378:metabolism*; D013858:Thiobarbiturates
D005290:Ferric Compounds; D005296:Ferrous Compounds; D006878:Hydroxides; D008054:Lipid Peroxides; D013858:Thiobarbiturates; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; C029684:thiobarbituric acid; D001205:Ascorbic Acid