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 Fe(3+) 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 Cu(2+), Fe(2+), or Fe(3+) 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:Fe(3+)] complexes but not the [deferoxamine:Fe(3+)] complex readily scavenged superoxide radicals. These results suggest that the initial step in superoxide radical scavenging (SRS) activity involves a redox-active flavonoid:Fe(3+) complex. Flavonoid:Fe(3+) complexes should, therefore, be tested as a therapy for the treatment of ischemia/reperfusion injury.
Moridani
Majid Y
MY
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Pourahmad
Jalal
J
Bui
Hoang
H
Siraki
Arno
A
O'Brien
Peter J
PJ
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D004032:Diet; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D007501:Iron / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology; D010636:Phenols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D005419:Flavonoids; D016166:Free Radical Scavengers; D010636:Phenols; D059808:Polyphenols; D013481:Superoxides; D003300:Copper; D007501:Iron; D014969:Xanthine Oxidase; D010100:Oxygen