The electrochemical analysis of cytochrome Р450 3А4 catalytic activity has shown that vitamins C, A and Е influence on electron transfer and Fe3+/Fe2+ reduction process of cytochrome Р450 3А4. These data allow to assume possibility of cross effects and interference of vitamins-antioxidants with drugs metabolised by cytochrome Р450 3А4, at carrying out of complex therapy. This class of vitamins shows antioxidant properties that lead to increase of the cathodic current corresponding to heme reduction of this functionally significant haemoprotein. Ascorbic acid of 0.028-0.56 mM concentration stimulates cathodic peak (an electrochemical signal) of cytochrome Р450 3А4. At the presence of diclofenac (Voltaren) - a typical substrate of cytochrome Р450 3А4 - the increase growth of a catalytic current testifying to an electrocatalysis and stimulating action of ascorbic acid is observed. In the presence of vitamins A and Е also is registered dose-dependent (in a range of 10-100 M) increase in a catalytic current of cytochrome Р450 3А4: the maximum increase corresponds to 229 ± 20% for 100 M of vitamin A, and 162±10% for 100 M of vitamin E. Vitamin E in the presence of P450's inhibitor itraconazole doesn't give essential increase in a reductive current, unlike retinol (vitamin A). This effect can manifest substrate properties of tocopherol (vitamin E). The electrochemical approach for the analysis of catalytic activity of cytochrome Р450 3А4 and studies of influence of biologically active compounds on an electrocatalysis is the sensitive and effective sensor approach, allowing to use low concentration of protein on an electrode (till 10-15 mol/electrode), to carry out the analysis without participation of protein redox partners, and to reveal drug-drug or drug-vitamins interaction in pre-clinical experiments.
Élektrokhimicheskiĭ analiz kataliticheskoĭ aktivnosti tsitokhroma R450 3A4 pokazal, chto vitaminy S, A i E vliiaiut na vosstanovlenie tsitokhroma R450 3A4. Poluchennye dannye pozvoliaiut predpolozhit' vozmozhnost' vzaimnogo vliianiia vitaminov i lekarstvennykh preparatov, metaboliziruemykh tsitokhromom R450 3A4, pri provedenii kompleksnoĭ terapii. Éti vitaminy proiavliaiut antioksidantnye svoĭstva, chto privodit k povysheniiu katodnogo toka, sootvetstvuiushchego vosstanovleniiu gema étogo funktsional'no znachimogo gemoproteina. Askorbinovaia kislota v kontsentratsii 0,028-0,56 mM stimuliruet katodnyĭ vosstanovitel'nyĭ pik (élektrokhimicheskiĭ signal) tsitokhroma R450 3A4. V prisutstvii diklofenaka - tipichnogo substrata tsitokhroma R450 3A4 - nabliudaetsia rost kataliticheskogo toka, svidetel'stvuiushchiĭ ob élektrokatalize i stimuliruiushchem deĭstvii askorbinovoĭ kisloty. V prisutstvii vitaminov A i E takzhe registriruetsia do zozavisimoe (v diapazone 10-100 mkM) uvelichenie kataliticheskogo toka tsitokhroma R450 3A4: maksimal'noe uvelichenie sostavliaet 229±20% dlia 100 mkM vitamina A, i 162±10% dlia 100 mkM vitamina E. V otlichie ot vitamina A, vitamin E v prisutstvii ingibitora itrakonazola ne daet sushchestvennogo uvelicheniia kataliticheskogo toka, chto mozhet ukazyvat' na proiavlenie substratnykh svoĭstv vitaminom E. Élektrokhimicheskiĭ podkhod dlia analiza kataliticheskoĭ aktivnosti tsitokhroma R450 3A4 i issledovaniia vliianiia biologicheski aktivnykh soedineniĭ na élektrokataliz iavliaetsia chuvstvitel'nym i éffektivnym sensornym podkhodom, pozvoliaiushchim ispol'zovat' nizkie kontsentratsii belka na élektrode (do 10-15 mol'/élektrod), provodit' analiz bez uchastiia belkov-partnerov i vyiavliat' vzaimodeĭstvie lekarstvennykh preparatov v doklinicheskikh éksperimentakh.
Keywords: C; E; antioxidants; cytochrome P450 3A4; diclofenac; electrochemistry; ferment electrodes; interaction; vitamins A.