An ESR study of the nitroxide radical of pentastarch-conjugated deferoxamine.
At higher concentrations, deferoxamine (DFO) reacts with hydroxyl radicals to produce a stable nitroxide free radical. Formation and decay of this nitroxide radical was investigated and compared with a novel modified pentastarch conjugate of DFO (MPS-DFO). Photolytic generation of hydroxyl radicals from H2O2 in the presence of free DFO produced a nitroxide radical with coupling constants of aN = 8.0 G and aH = 6.5 G. Under the same experimental conditions, equimolar concentrations of MPS-DFO produced an ESR signal of reduced intensity while iron-saturated MPS-DFO produced no signal. Incubation of free DFO with pentastarch (i.e., without conjugation) greatly decreased the intensity of the nitroxide radical signal. Using a spin-trapping technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), the pentastarch vehicle was shown to inhibit the DMPO-OH adduct formation. The decay of the DFO nitroxide radical decayed with a second-order rate constant while that of MPS-DFO decayed with a first-order rate constant. Thus, a novel derivative of DFO may provide some additional benefit in limiting DFO nitroxide radical formation and might explain the reported reduced in vivo toxicity of MPS-DFO relative to free DFO.
Pieper
G M
GM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
Kalyanaraman
B
B
D003676:Deferoxamine / Q000378:metabolism*; D003855:Deoxyribose / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide / Q000378:metabolism; D006868:Hydrolysis; D006878:Hydroxides; D017665:Hydroxyl Radical; D009589:Nitrogen Oxides / Q000378:metabolism*
D016166:Free Radical Scavengers; D006878:Hydroxides; D009589:Nitrogen Oxides; D017665:Hydroxyl Radical; D003855:Deoxyribose; D006861:Hydrogen Peroxide; C039900:nitroxyl; D003676:Deferoxamine