Desferrioxamine (DFO) conjugated with starch decreases NAD redox potential of intact red blood cells (RBC): evidence for DFO as an extracellular inducer of oxidant stress in RBC.
Desferrioxamine (DFO) is an important iron-chelating agent. It has also been thought of as an agent with anti-oxidant potential as it chelates ferric iron in various parts of the body. However, there is evidence suggesting that it may paradoxically affect red blood cells (RBCs) by inducing intracellular oxidant stress. Recently we observed that incubation of RBCs with DFO decreases NAD redox potential in normal RBC. To further understand the mechanism of DFO's interaction with RBC, we conducted a study to determine the effect of extracellular DFO upon RBC's redox status. We examined NAD redox potential in intact RBC (N = 7) incubated with DFO conjugated to starch. RBCs were incubated with 4 mM DFO for 3(1/2) hr and with 6 mM DFO for 2 and 3(1/2) hr. Significant decreases in NAD redox potential were observed after the incubations. With 4 mM DFO at the 3 (1/2) hr time point the mean decrease was 12.37% +/- 9.96% (P < 0.0085). With 6 mM DFO, the mean decreases were 18.54% +/- 9.79% (P < 0.0013) and 19.16% +/- 8.78% (P < 0.0006) for the 2 and 3 (1/2) hr incubations, respectively. DFO by itself is very poorly permeable to RBC. Conjugation with starch further ensured impermeability of DFO. The data presented here confirm the oxidant effect of DFO on RBC. The data also demonstrate that the effect of DFO on RBC's NAD redox potential originates extracellularly.
Niihara
Y
Y
Department of Medicine, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, California, USA. ysniihara@msn.com
Shalev
O
O
Hebbel
R P
RP
Wu
H
H
Tu
A
A
Akiyama
D S
DS
Tanaka
K R
KR
D000328:Adult; D002614:Chelating Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D013213:Starch / Q000494:pharmacology*
D002614:Chelating Agents; D009243:NAD; D013213:Starch; D003676:Deferoxamine