Human Red Blood Cells as A Natural Flavonoid Reservoir

Abstract

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.

Protective Effects of Resveratrol and Quercetin Against MPP+ -Induced Oxidative Stress Act by Modulating Markers of Apoptotic Death in Dopaminergic Neurons

“…Recent studies have demonstrated that in humans flavonoids, such as quercetin and resveratrol, are readily absorbed and that their bioavailability is much greater than previously believed (Ross and Kasum 2002). Concentration of flavonoids in human plasma varies from 3 to 30 mM and certainly more if the red blood cell associated flavonoids are taken into account (Fiorani et al 2003). Interestingly, new studies in pigs report that long-term dietary intake of quercetin did not lead to a greater accumulation in any tissue compared with a single treatment.…”

Bioavailability of Apigenin from Apiin-Rich Parsley in Humans

“…This fi nding supports the hypothesis that certain fl avonoids, including apigenin, may contribute to the cellular antioxidant defense system [21] or may reveal other biological effects as found in test systems (see Introduc-tion). Fiorani et al [22] found that quercetin is effi ciently taken up by human RBC via passive diffusion resulting in an accumulation of the fl avonoid in body cells. The substance was utilized as substrate for a trans-plasma membrane oxidoreductase contributing to the reduction of extracellular oxidants.…”

“…Due to the structural similarity between quercetin and apigenin, these results can probably be transferred to the group of fl avones as well. It has been suggested that human RBC could play a pivotal role in the distribution and bioavailability of circulating fl avonoids [22] .…”

Protein Kinases and Protein Phosphatases as Participants in Signal Transduction of Erythrocytes

“…The erythrocyte has a pool of flavonic compounds, which are considered a buffer, maintaining the antioxidative activity of the erythrocyte (Fiorani et al, 2003) Quercetin and resveratrol (piceatannol) take part in the regulation of the phosphorylation of band 3 in the presence of the physiological oxidant peroxinitrite. Quercetin decreases the Syk activity and particularly prevents mediated by the free radical peroxynitrite (ONOO . )…”