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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 Ca²⁺ (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 Ca²⁺ ions. Since Ruthenium red, an inhibitor of the mitochondrial Ca²⁺ uniporter, effectively prevented Ca²⁺-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 Ca²⁺ uniporter.Tsel' nastoiashcheĭ raboty — vyiasnit' mekhanizmy narusheniĭ struktury i funktsional'noĭ aktivnosti izolirovannykh mitokhondriĭ pecheni krys ionami kal'tsiia v otsutstvie i v prisutstvii riada flavonoidov in vitro. V prisutstvii ékzogennogo Ca²⁺ (20-60 mkM) vyrazhenno vozrastala geterogennost' mitokhondriĭ po razmeram i élektronnoĭ plotnosti. Bol'shinstvo organell kharakterizovalos' nabukhshim élektronno-svetlym matriksom, udlinennymi kristami i umen'shennym ikh chislom. Nabukhshie mitokhondrii byli znachitel'no krupnee osnovnoĭ populiatsii kontrol'nykh mitokhondriĭ i lisheny nativnoĭ struktury vnutrenneĭ membrany, vplot' do ee otsloeniia. Odnovremenno registrirovali kondensirovannye mitokhondrii s élektronno-plotnym matriksom i rasshirennym intrakristnym prostranstvom. Indutsiruemoe ionami kal'tsiia otkrytie mitokhondrial'nykh por vysokoĭ pronitsaemosti (MPTP) privodilo k ul'trastrukturnym narusheniiam organell i soprovozhdalos' polnym razobshcheniem protsessov okisleniia i fosforilirovaniia v izolirovannykh mitokhondriiakh pecheni krys. Vtorichnye metabolity rasteniĭ polifenol'noĭ prirody — flavonoidy naringenin, katekhin — v kontsentratsii 10-25 mkM dozozavisimo ingibirovali respiratornuiu aktivnost' mitokhondriĭ i stimulirovali protsess otkrytiia MPTP v prisutstvii ionov Ca²⁺. Poskol'ku ruteniĭ krasnyĭ — ingibitor mitokhondrial'nogo Ca²⁺ uniportera — éffektivno predotvrashchal Ca²⁺-indutsiruemoe otkrytie MPTP kak v otsutstvie, tak i v prisutstvii flavonoidov, mozhno predpolozhit', chto éffekt flavonoidov na protsess MPTP oposredovan aktivatsieĭ Ca²⁺ uniportera. |
