Catecholic iron complexes as cytoprotective superoxide scavengers against hypoxia:reoxygenation injury in isolated hepatocytes.
Reactive oxygen species including superoxide radicals (O2-.) have been implicated in the pathogenesis of radiotherapy, ischemia-reperfusion injury, aging, and inflammatory diseases. In the present work, 2:1 catecholic iron complexes were found to be more effective than uncomplexed catechols at protecting hepatocytes against hypoxia:reoxygenation cell injury. They also decreased markedly the level of reactive oxygen species formed before cytotoxicity ensued. Furthermore, these catecholic iron complexes were also more effective than uncomplexed catechols at scavenging superoxide radicals generated both enzymatically and nonenzymatically. The superoxide radical scavenging activity of catecholic iron complexes seemed to correlate with the redox potential of catechols. These results suggest that cytoprotection by catechols may involve an initial chelation with iron to form a complex that is a much more effective superoxide radical scavenger than the catechol itself.
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Z S
ZS
Zhao
S
S
Khan
P J
PJ
O'Brien
D000818:Animals; D002396:Catechols / Q000378:metabolism* / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D002396:Catechols; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D013481:Superoxides; D010100:Oxygen