Desferrioxamine (DFO) conjugated with starch decreases NAD redox potentialof 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 bee n 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 th at it may paradoxically affect red blood cells (RBCs) by inducing intracell ular oxidant stress. Recently we observed that incubation of RBCs with DFO decreases NAD redox potential in normal RBC. To further understand the mech anism 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. RB Cs were incubated with 4 mM DFO for 3 1/2 hr and with 6 mM DFO for 2 and 3% hr. Significant decreases in NAD redox potential were observed after the i ncubations. 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 dat a presented here confirm the oxidant effect of DFO on RBC. The data also de monstrate that the effect of DFO on RBC's NAD redox potential originates ex tracellularly. (C) 2000 Wiley-Liss, Inc.