title: Ability of ferric nitrilotriacetate complex with three pH-dependent conformations to induce lipid peroxidation.
abstract: This study examined the generation of reactive oxygen species (ROS) and the induction of lipid peroxidation by carcinogenic iron(III)-NTA complex (1:1), which has three conformations with two pKa values (pKa1 approximately 4, pKa2 approximately 8). These conformations are type (a) in acidic conditions of pH 1-6, type (n) in neutral conditions of pH 3-9, and type (b) in basic conditions of pH 7-10. The iron(III)-NTA complex was reduced to iron(II) complex under cool-white fluorescent light without the presence of any reducer. The reduction rates of three species of iron(III)-NTA were in the order type (a) >> type (n) > type (b). Iron(III)-NTA-dependent lipid peroxidation was induced in the presence and absence of preformed lipid peroxides (L-OOH) through processes associated with and without photoreduction of iron(III). The order of the abilities of the three species of iron(III)-NTA to initiate the three mechanisms of lipid peroxidation was: (1) type (a) > type (n) > type (b) in lipid peroxidation that is induced L-OOH- and H2O2-dependently and mediated by the photoreduction of iron(III); (2) type (b) > type (n) > type (a) in lipid peroxidation that is induced L-OOH- and H2O2-dependently but not mediated by the photoreduction of iron(III); (3) type (n) > type (b) > type (a) in lipid peroxidation that is induced peroxide-independently and mediated by the photoactivation but not by the photoreduction of iron(III). The rate of lipid peroxidation induced L-OOH-dependently is faster than that induced H2O2-dependently in the mechanism (1), but the rate of lipid peroxidation induced H2O2-dependently is faster than that induced L-OOH-dependently in the mechanism (2). In the lag process of mechanism (3), L-OOH and/or some free radical species, not 1O2, were generated by photoactivation of iron(III)-NTA. These multiple pro-oxidant properties that depend on the species of iron(III)-NTA were postulated to be a principal cause of its carcinogenicity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Akai
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Akira
authors.initials: A
authors.lastname: Tokumura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kogure
authors.forename: Satoru
authors.initials: S
authors.lastname: Ueno
authors.forename: Akira
authors.initials: A
authors.lastname: Shibata
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukuzawa
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation / Q000528:radiation effects; D008054:Lipid Peroxides / Q000737:chemistry; D008823:Micelles; D008968:Molecular Conformation; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D010084:Oxidation-Reduction; D010777:Photochemistry; D014466:Ultraviolet Rays; D024502:alpha-Tocopherol / Q000737:chemistry; D019207:beta Carotene / Q000737:chemistry
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D005290:Ferric Compounds; D008054:Lipid Peroxides; D008823:Micelles; D019207:beta Carotene; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate