Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid.
A breakdown in homeostasis of redox-active metals represents an important factor for neurodegeneration. We have used EPR spectroscopy and BMPO spin-trap to investigate the catalytic properties and ligand modulation of redox activity of copper and iron in human cerebrospinal fluid (CSF). In contrast to iron, copper supplementation provoked a statistically significant increase in hydroxyl free radical generation in CSF treated with H(2)O(2). However, in a binary copper/iron containing Fenton system, iron catalytically activated copper. The chelator EDTA, which represents a model of physiological metal ligands, completely prevented copper's redox activity in CSF, while iron chelation led to a significant increase in hydroxyl radical generation, indicating that copper and iron do not only have diverse catalytic properties in the CSF but also that their redox activities are differently modulated by ligands. The application of DDC reduced hydroxyl radical generation in the CSF containing catalytically active metals (free Cu(2+) or Fe(3+)-EDTA complex). We conclude that chelators, such as DDC, are capable of preventing the prooxidative activity of both metals and may be suitable for reducing hydroxyl radical formation in certain pathophysiological settings.
Spasojević
Ivan
I
Institute for Multidisciplinary Research, University of Belgrade, 11000 Belgrade, Serbia. ivan@cms.bg.ac.rs
Mojović
Milos
M
Stević
Zorica
Z
Spasić
Snezana D
SD
Jones
David R
DR
Morina
Arian
A
Spasić
Mihajlo B
MB
D000328:Adult; D001682:Biological Availability; D002384:Catalysis; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000134:cerebrospinal fluid* / Q000737:chemistry; D003497:Cyclic N-Oxides; D004050:Ditiocarb / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006878:Hydroxides / Q000737:chemistry; D007501:Iron / Q000134:cerebrospinal fluid* / Q000737:chemistry; D008297:Male; D008875:Middle Aged
C441196:5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide; D002614:Chelating Agents; D003497:Cyclic N-Oxides; C045076:Fenton's reagent; D005609:Free Radicals; D006878:Hydroxides; D003300:Copper; C031356:hydroxide ion; D004050:Ditiocarb; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D007501:Iron