The flavonoids fisetin, apigenin, kaempferol, naringenin, naringin regulate respiratory activity and membrane potential of rat liver mitochondria and inhibit oxidative processes in erythrocytes

Flavonoids, secondary plant metabolites, represent the most abundant heterogeneous group of phytochemicals. The aim of this study to compare antioxidant activity and regulatory properties of several representatives of different classes of flavonoids, fisetin, apigenin, kaempferol, naringenin, naringin, using liver mitochondria and erythrocytes as research objects. In the concentration range of 2.5-25 μM fisetin, apigenin, kaempferol, naringenin, and naringin dose-dependently prevented oxidative damage of erythrocytes induced by 700 μM tert-butyl hydroperoxide: accumulation of lipid peroxidation (LPO) products and oxidation of glutathione GSH. The IC50 values corresponding to the flavonoid concentration inhibiting the LPO process in erythrocyte membranes by 50%, were 3.9±0.8 μM in the case of fisetin, 6.5±1.6 μM in the case of kaempferol, 8.1±2.1 μM in the case of apigenin, 37.8±4.4 μM in the case of naringenin, and 64.7±8.6 μM in the case of naringin. The antioxidant effect of flavonoids was significantly higher in the membrane structures compared to the cytoplasm of cells. All flavonoids studied (10-50 μM) effectively inhibited the respiratory activity of isolated rat liver mitochondria and, with the exception of kaempferol, stimulated Ca²⁺-induced dissipation of the mitochondrial membrane potential. Cyclosporine A and ruthenium red inhibited flavonoid-stimulated Ca²⁺-dependent membrane depolarization, thus indicating that the mitochondrial calcium uniporter and the mitochondrial permeability transition pore opening were involved in the flavonoid effects. Flavonoids, as the redox-active compounds with antioxidant properties, are able to regulate mitochondrial potential and respiratory activity, and prevent mitochondrial oxidative stress. They can be considered as effective pharmacological agents or nutraceuticals.