Ferrous and ferric chelation activity of selected natural flavonoids

Iron overload both following transfusion therapy of thalassemia and as the result of an inherited disorder, is associated with tissue damage and increased mortality. Patients suffering from iron overload can be treated by administration of iron chelators. Because of some limitations of commonly used iron chelators, the research of new iron chelators is required. In this pilot study, eight flavonoids of different basic structure and two synthetic iron chelators from aroylhydrazone group (SIH, PIH) were compared with effect of clinically used deferoxamine (DEF). Ferrous and total iron chelation activity was assessed by a simple spectrophotometric assay. Shortly: Potential iron chelators were mixed with ferrous or ferric ions in various ratios. Concentration of unbound iron was established by ferrozine at 562nm. Because ferrozine colours specifically ferrous ions, in case of ferric ions, hydroxylamine 10 mM was used for their reduction. None of tested chelators was similarly effective ferrous chelator as compared with DEF. Interestingly, apigenin was more active than synthetic chelators PIH and SIH and rutin was more effective than SIH. Other flavonoids showed only negligible activity. On the contrary, ferric ions seemed to be chelated absolutely by synthetic iron chelators PIH and SIH in ratio 10:1, chelator: iron, respectively. DEF was more effective since its activity nears 100% in ratio 1:1. Tested flavonols (rutin, kaempferol and 3-OH flavone) together with flavone apigenin brought about significant ferric chelation while flavanones (hesperetin and naringenin) with flavanols (catechin and epicatechin) were again practically inactive. This study demonstrated that some flavonoids, especially flavonols, act as iron chelators in clinically relevant concentrations. Though their effect did not approached DEF and synthetic chelators, it should be taken in consideration that additionally to their antioxidant properties they may be useful in pathological conditions associated with oxidative stress due to catalytical role of iron.

Acknowledgements: This work was supported by a grant of Charles University No. 53707/B/FaF.