Possible Interaction: Deferoxamine and Ascorbate

“Some samples stimulated formation of hydroxyl radicals from H2O2 in the presence of ascorbate , a reaction again inhibited by desferrioxamine.”

“However, brief pre-treatment with a pharmacological dose (250-750 μM) of l-ascorbate immediately prior to NTP exposure significantly increased its cytotoxicity in a dose-dependent manner, which was inhibited by the iron chelator, deferoxamine.”

“These effects were consistant with the notion that deferoximine and ascorbate can act as a prooxidant couple.”

“This conclusion was confirmed when we measured the oxidative activities of the system using nitroblue tetrazolium and cytochrome c. Indeed, we noted that deferoximine markedly activates the autocatalytic oxidation of ascorbate.”

“Using alkaline phosphatase extracted from chick cartilage, we noted that the activity of the phosphatase was markedly reduced in the presence of deferoximine and ascorbate.”

“We next examined the possibility that deferoximine , in the presence of ascorbate , could form a free radical system that would serve to inactivate the enzyme.”

“ Desferrioxamine , by acting intracellularly unlike other agents used, might prevent the reduction of Fe(+3) by ascorbate and superoxide anion thus inhibiting the formation of cytotoxic hydroxyl radical in this experimental setting.”

“Both bathocuproine and desferrioxamine blunted the postreperfusion increase in ascorbate free radical generation: no drug, 36+/-8% increase; desferrioxamine, 13+/-5% increase; bathocuproine, 21+/-6% increase (p < 0.05 vs. baseline).”

“ Ascorbate had a mild prooxidant effect as a sole additive to the UW gluconate solution but was clearly prooxidant when combined with either deferoxamine or Trolox.”

“ DFO (25 mg/kg) decreased BALF protein concentration (p < 0.05) and was associated with higher BALF ascorbate concentrations (p < 0.01) in O3-exposed animals.”

“The restoration of the cytotoxic action of H2O2 at 4 degrees C by ascorbate is prevented by pre-exposure of cells to desferrioxamine.”

“Addition of deferoxamine completely inhibited both ferrous ascorbate , 1:20 and ferric nitrilotriacetate-induced lipid peroxidation, demonstrating the requirement for iron for its stimulation.”

“A synergistic effect of DFOB and ascorbate on the rate of goethite dissolution was observed (total rates greater than the sum of the individual rates), and this effect was most pronounced under oxic conditions.”