Membrane cholesterol contents modify the protective effects of quercetin and rutin on integrity and cellular viability in oxidized erythrocytes

Flavonoids protect cells damaged by oxidative stress. This, together with other biological activities, is governed by structural features of flavonoids and the nature and physical state of the cell membrane. We have previously proved that membrane cholesterol contents modify the protective power of quercetin and rutin against oxidative stress in erythrocytes. Here we analyzed the lipid asymmetry, the integrity, and cell viability of native and cholesterol-modified erythrocytes exposed to tert-butyl hydroperoxide in presence of both antioxidants. Our results provides clear evidence that quercetin affords better protection than rutin against lipid peroxidation, ROS generation, erythrophagocytosis and cellular instability in oxidized erythrocytes with normal and modified cholesterol contents. Both antioxidants provided a high of protection for the transbilayer aminophospholipid asymmetry, only partly preserving cell morphology in oxidized control and cholesterol-depleted erythrocytes. Cholesterol depletion reduced the protection provided by both antioxidants against phosphatidylserine externalization, erythrophagocytosis and hemolysis, which is in accordance with the lower degree of preservation against lipid peroxidation observed in oxidized cholesterol-depleted erythrocytes. This lower degree of preservation is presumably attributable to the low antioxidant contents in these erythrocyte membranes, or even to a lower efficiency of the antioxidant in a modified lipid environment due to the removal of cholesterol.