The dose-dependent influence of antioxidant vitamins on electrochemically-driven cytochrome P450 3A4 catalysis

Abstract

Victoria V. Shumyantseva, Anna A. Makhova, Tatyana V. Bulko,Alexey V. Kuzikov, Evgeniya V. Shich, Elena V. Suprun,Vladimir Kukes, Sergei Usanov , Alexander Archakov

Electrochemical analysis of the catalytic activity of cytochrome P450 3A4 has shown that vitamins C, A and E exert influence on the Fe3+ /Fe2+ reduction process of this enzyme. Direct electron transfer of cytochrome P450 3A4 was investigated by use of cyclic voltammetry and square wave voltammetry. The increase of the reduction peak current in the presence of vitamins C, A and E appears to be associated with antioxidant properties of these vitamins. Vitamin C (in the range of 0.03-1 mM), vitamins A and E (in the range of 10-100 µM) stimulated the dose-dependent growth of the cathodic peak current of cytochrome P450 3A4. The electrochemical analysis of the catalytic activity of cytochrome P450 3A4 offers an unorthodox and efficient approach to pre-clinical registration of drug-drug and drug-vitamin interactions via the respective electrochemical responses.