OBJECTIVES: This study is an extension to our finding of direct anti-oxidant activities of lanthanide(III) complexes with the heterocyclic compound, 5-aminoorotic acid (AOA). In this experiment, we used AOA and coumarin-3-carboxylic acid as the two heterocyclic compounds with anti-oxidant potential, to produce the complexes with different lanthanides. METHODS: Lanthanide(III) complexes were tested on the iron-driven Fenton reaction. The product of this reaction, the hydroxyl radical, was detected by HPLC. RESULTS: All complexes as well as their ligands had positive or neutral effect on the Fenton reaction but their behavior was different. Both pure ligands in low concentration ratio to iron were inefficient in contrast to some of their complexes. Complexes of neodymium, samarium, gadolinium, and partly of cerium blocked the Fenton reaction at very low ratios (in relation to iron) but the effect disappeared at higher ratios. In contrast, lanthanum complexes appeared to be the most promising. Both blocked the Fenton reaction in a dose-dependent manner. CONCLUSION: Lanthanide(III) complexes were proven to block the iron-driven production of the hydroxyl radical. Second, the lanthanide(III) element appears to be crucial for the anti-oxidant effect. Overall, lanthanum complexes may be promising direct anti-oxidants for future testing.

b Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského 1203 500 05 Czech Republic

c Department of Physiology and Pharmacology 'Vittorio Erspamer' Sapienza University of Rome Piazzale Aldo Moro 5 00185 Italy

Department of Chemistry Faculty of Pharmacy Medical University 2 Dunav Street Sofia 1000 Bulgaria

Department of Pharmacognosy Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského 1203 500 05 Czech Republic

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