Dietary flavonoid iron complexes as cytoprotective superoxide radical scavengers

Superoxide radicals have been implicated in the pathogenesis of ischemia/reperfusion, aging, and inflammatory diseases. In the present work, we have shown that the Fe3+ complexes of flavonoids (polyphenols) were much more effective than the uncomplexed flavonoids in protecting isolated rat hepatocytes against hypoxia-reoxygenation injury. The 2:1 flavonoid-metal complexes of Cu2+, Fe2+, or Fe3+ were more effective than the parent compounds in scavenging superoxide radicals generated by xanthine oxidase/hypoxanthine (an enzymatic superoxide-generating system). The 2:1 [flavonoid:Fe3+] complexes but not the [deferoxamine:Fe3+] complex readily scavenged superoxide radicals. These results suggest that the initial step in superoxide radical scavenging (SRS) activity involves a redox-active flavonoid:Fe3+ complex. Flavonoid:Fe3+ complexes should, therefore, be tested as a therapy for the treatment of ischemia/reperfusion injury.