Human red blood cells as a natural flavonoid reservoir

Quercetin is rapidly and avidly taken up by human red blood cells (RBC) via a passive diffusion mechanism, driven by flavonoid binding to haemoglobin and resulting in an almost quantitative accumulation of the flavonoid. Heamoglobin-free resealed ghosts accumulated quercetin exclusively in the membrane fraction. Cell-associated quercetin was biological active and could be quantitatively utilised to support the reduction of extracellular oxidants mediated by a transplasma-membrane oxido-reductase. Additional experimental evidence revealed that quercetin uptake declined in the presence of albumin and that, under these conditions, the amount of cell-associated quercetin is enhanced by increasing the RBC number. Quercetin release from flavonoid-preloaded RBC was observed only in the presence of albumin (or in human plasma) and this response was progressively inhibited upon incubation in solutions containing albumin previously exposed to increasing concentrations of quercetin and cleared of the unbound fraction of the flavonoid. Furthermore, exposure to quercetin pre-saturated albumin promoted accumulation of the flavonoid in fresh RBC and this response was a direct function of the extent of albumin saturation. These results, indicating a flow of quercetin from albumin to haemoglobin, and vice versa, are therefore consistent with the possibility that human RBC play a pivotal role in the distribution and bioavailability of circulating flavonoids.