Copyright: © 2017 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).

ORIGINAL RESEARCH

Analysis of mildronate effect on the catalytic activity of cytochrome Р450 3А4

About authors

1 Laboratory of Bioelectrochemistry, Department of Personalized Medicine,
Institute of Biomedical Chemistry, Moscow, Russia

2 Department of Biochemistry, Biomedical Faculty,
Pirogov Russian National Research Medical University, Moscow, Russia

3 Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Faculty of General Medicine,
I. M. Sechenov First Moscow State Medical University, Moscow, Russia

4 Institute of Bioorganic Chemistry of the National Academy of Sciences, Minsk, Republic of Belarus

Correspondence should be addressed: Victoria Shumyantseva
ul. Pogodinskaya, d. 10, Moscow, Russia, 119121; ur.liam@avestnaymuhs_v

About paper

Funding: this work was conducted under the Federal Fundamental Scientific Research Program for 2013–2020.

Received: 2016-11-28 Accepted: 2016-12-06 Published online: 2017-01-19
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Fig. 1. Electron transfer in a P450-containing monooxygenase system (top) and an electrochemical system (bottom)
Protein structure images — courtesy of PDB database [16], NADPH image — courtesy of PubChem [17].
Fig. 2. Cyclic voltammograms of cytochrome Р450 3A4 (––) and in the presence of 75 μM mildronate (– –)
The enzyme was immobilized on the electrode modified with DDAB. Scan range: from 0 to –0.6 V (vs. Ag/AgCl); scan rate: 0.05 V/s.
Fig. 3. Dependence of Р450 3A4 reduction current (%) on mildronate concentration (μM), obtained from cyclic voltammetry data. Scan range: from 0 to –0.6 V (vs. Ag/AgCl); scan rate: 0.05 V/s
Fig. 4. Peak currents on square-wave voltammograms under aerobic conditions: (1) P450 3А4; (2) P450 3А4 + diclofenac; (3) P450 3А4 + itraconazole; (4) P450 3А4 + itraconazole + diclofenac; (5) P450 3А4 + erythromycin; (6) P450 3А4 + L-carnitine; (7) P450 3А4 + L-carnitine + diclofenac; (8) P450 3А4 + lipoic (thioctic) acid
Values of current amplitudes were baseline-corrected.
Kinetic parameters of P450 3А4-dependent electrocatalytic N-demethylation of erythromycin
Note. Electrolysis was performed at controlled voltage of –0.5 V (vs. Ag/AgCl) for 20 min in the presence of 100 μM erythromycin.