Rheological changes in human red blood cells under oxidative stress: effects of thiol-containing antioxidants

Thiol-compounds, dithiothreitol (DTT) and N-acetylcysteine (NAC), were examined for their antioxidant effects on Fe2+/ascorbate-treated and diamide-treated red blood cells (RBCs). Both of the compounds protected RBCs against diamide-induced spectrin crosslinking; they also prevented loss of deformability and aggregation impairment in diamide-treated cells. Neither DTT nor NAC were effective in suppressing lipid peroxidation induced by Fe2+/ascorbate treatment. DTT showed a limited protective effect on iron-mediated band 3 fragmentation and RBC deformability, but it was capable of preventing the decrease of rouleaux formation rate to some extent. NAC exhibited a dose-dependent band 3 protective activity, partially prevented Fe2+/ascorbate-induced deformability impairment and the decrease of rouleux formation rate. These findings suggest that thiol compounds are effective in modulating diamide-induced oxidative alterations of RBCs membrane constituents and rheological properties. NAC is more efficacious than DTT in protecting RBCs against iron-mediated oxidative injury, which can be attributed to its potent reductant and radical scavenging abilities.