title: Effects of citrinin on iron-redox cycle.
abstract: The ability of the mycotoxin citrinin to act as an inhibitor of iron-induced lipoperoxidation of biological membranes prompted us to determine whether it could act as an iron chelating agent, interfering with iron redox reactions or acting as a free radical scavenger. The addition of Fe3+ to citrinin rapidly produced a chromogen, indicating the formation of citrinin-Fe3+ complexes. An EPR study confirms that citrinin acts as a ligand of Fe3+, the complexation depending on the [Fe3+]:[citrinin] ratios. Effects of citrinin on the iron redox cycle were evaluated by oxygen consumption or the o-phenanthroline test. No effect on EDTA-Fe2+-->EDTA-Fe3+ oxidation was observed in the presence of citrinin, but the mycotoxin inhibited, in a dose-dependent manner, the oxidation of Fe2+ to Fe3+ by hydrogen peroxide. Reducing agents such as ascorbic acid and DTT reduced the Fe3+-citrinin complex, but DTT did not cause reduction of Fe3+-EDTA, indicating that the redox potentials of Fe3+-citrinin and Fe3+-EDTA are not the same. The Fe2+ formed from the reduction of Fe3+-citrinin by reducing agents was not rapidly reoxidized to Fe3+ by atmospheric oxygen. Citrinin has no radical scavenger ability as demonstrated by the absence of DPPH reduction. However, a reaction between citrinin and hydrogen peroxide was observed by UV spectrum changes of citrinin after incubation with hydrogen peroxide. It was also observed that citrinin did not induce direct or reductive mobilization of iron from ferritin. These results indicate that the protective effect on iron-induced lipid peroxidation by citrinin occurs due to the formation of a redox inactive Fe3+-citrinin complex, as well as from the reaction of citrinin and hydrogen peroxide.
authors.affiliation: Departamento de Bioquímica da Universidade Federal do Paraná, Curitiba, Brasil.
authors.forename: Eneida Janiscki
authors.initials: EJ
authors.lastname: Da Lozzo
authors.forename: Antonio Salvio
authors.initials: AS
authors.lastname: Mangrich
authors.forename: Maria Eliane Merlin
authors.initials: ME
authors.lastname: Rocha
authors.forename: Maria Benigna Martinelli
authors.initials: MB
authors.lastname: de Oliveira
authors.forename: Eva Gunilla Skare
authors.initials: EG
authors.lastname: Carnieri
mesh_terms: D001205:Ascorbic Acid / Q000378:metabolism; D002953:Citrinin / Q000378:metabolism / Q000494:pharmacology*; D004229:Dithiothreitol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004492:Edetic Acid / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000378:metabolism*; D005296:Ferrous Compounds / Q000378:metabolism*; D005297:Ferrozine / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010618:Phenanthrolines / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D005609:Free Radicals; D007502:Iron Chelating Agents; D008024:Ligands; D010618:Phenanthrolines; D005297:Ferrozine; D002953:Citrinin; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D010100:Oxygen; D004229:Dithiothreitol; C025205:1,10-phenanthroline