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 Ca²âº-induced dissipation of the mitochondrial membrane potential. Cyclosporine A and ruthenium red inhibited flavonoid-stimulated Ca²âº-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.

[Structural and functional changes in rat liver mitochondria under calcium ion loading in the absence and presence of flavonoids]. / Strukturnye i funktsional'nye izmeneniia mitokhondrii pecheni krys pri nagruzke ionami kal'tsiia v otsutstvie i v prisutstvii flavonoidov.

The aim of the present work was to elucidate the mechanisms of calcium ion-induced impairments of the ultrastructure and functional activity of isolated rat liver mitochondria in the absence and presence of a number of flavonoids in vitro. In the presence of exogenous Ca²âº (20-60 µM), mitochondrial heterogeneity in size and electron density markedly increased: most organelles demonstrated a swollen electron-light matrix, bigger size, elongated cristae and a reduced their number, a damaged native structure of the inner membrane up to its detachment, and some mitochondria showed a more electron-dense matrix (condensed mitochondria). The calcium-induced opening of the mitochondrial permeability transition pores (MPTP) resulted in the ultrastructural disturbances and in the effective inhibition of the respiratory activity of rat liver mitochondria. The flavonoids (10-25 µM) naringenin and catechin, dose-dependently inhibited the respiratory activity of mitochondria and stimulated the MPTP opening in the presence of Ca²âº ions. Since Ruthenium red, an inhibitor of the mitochondrial Ca²âº uniporter, effectively prevented Ca²âº-induced MPTP opening both in the absence and presence of flavonoids, we hypothesized that the effect of flavonoids on the MPTP opening could be mediated by stimulation of the Ca²âº uniporter.