ISSN Print 2500–1094
ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
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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In this work, we have studied the effect of mildronate on the catalytic properties of cytochrome Р450 3А4. The analysis of the catalytic activity was carried out using electrochemical methods, with cytochrome Р450 3А4 immobilized on the electrode surface. In the presence of 50 μM mildronate, no increase was observed in the turnover number of cytochrome Р450 3А4-dependent N-demethylation of erythromycin. The values of the turnover number kcat calculated from the product formed by the reaction were 6.1 ± 0.6 min–1 (Р450 3А4 + erythromycin) and 5.5 ± 1.4 min–1 (Р450 3А4 + erythromycin + mildronate). Thus, electroanalysis of cytochrome Р450 3А4 catalytic activity demonstrated the possibility of a safe and effective complex drug therapy with concurrent administration of mildronate and the macrolide (erythromycin).
Keywords: cytochrome Р450 3А4, antihypoxic drugs, electroanalysis, enzyme electrodes, drug interference, mildronate