http://www3.interscience.wiley.com/cgi-bin/abstract/85514985/ABSTRACT Cell Biochemistry and Function Volume 20, Issue 1 , Pages 19 - 29 Published Online: 8 Oct 2001 Copyright © 2002 John Wiley & Sons, Ltd. Research Article Effects of citrinin on iron-redox cycle Eneida Janiscki Da Lozzo 1, Antonio Salvio Mangrich 2, Maria Eliane Merlin Rocha 1, Maria Benigna Martinelli de Oliveira 1, Eva Gunilla Skare Carnieri 1 * 1Departamento de Bioquímica da Universidade Federal do Paraná, Curitiba, Brasil 2Departamento de Química da Universidade Federal do Paraná, Curitiba, Brasil email: Eva Gunilla Skare Carnieri (carnieri@bio.ufpr.br) *Correspondence to Eva Gunilla Skare Carnieri, Departamento de Bioquímica da Universidade Federal do Paraná, CP 19046, CEP 81531-990, Curitiba, PR, Brasil. Funded by: CNPq Keywords citrinin, iron chelation; iron redox cycle; iron-dependent lipid peroxidation 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. Copyright © 2001 John Wiley & Sons, Ltd.Abbreviations used: DPPH diphenylpicrylhydrazyl DMPO 5,5-dimenthyl-1-pyrroline-N-oxide EDTA ethylene diaminetetraacetic acid DTT dithiothreitol EPR electron paramagnetic resonance spectroscopy