Advertisement

BioNanoScience

, Volume 9, Issue 1, pp 79–86 | Cite as

Bioelectrochemical Systems as Technologies for Studying Drug Interactions Related to Cytochrome P450

  • Victoria V. ShumyantsevaEmail author
  • Anna A. Makhova
  • Evgenia V. Shikh
  • Tatiana V. Bulko
  • Alexey V. Kuzikov
  • Rami A. Masamrekh
  • Tatyana Shkel
  • Sergey Usanov
  • Andrei Gilep
  • Alexander I. Archakov
Article
  • 52 Downloads

Abstract

The electrocatalytic activity of cytochrome P450 3A4 as the main enzyme of drug metabolism was studied. Cytochrome P450 electrodes allowed to register 10−11–10−12 mol of enzyme/electrode. The study has shown that the developed electrochemical systems based on cytochromes P450 are effective non-invasive models for the analysis of drug–drug interactions at the level of biotransformation of xenobiotics. The effect of clinically significant drug combinations on the activity of cytochrome P450 3A4 was studied. The electroanalytical response of cytochrome P450 3A4 enzyme was interpreted in terms of its impact on drug interference and assessment of heme protein activity. The results can be used for modulation of cytochrome P450 activity in case of comorbid patients with polypharmacy.

Keywords

Cytochrome P450 Bioelectrochemistry Mechanism-based modulators Electroanalysis Drug interactions Complex pharmacotherapy Comorbid patients Polypharmacy Therapeutic window 

Notes

Acknowledgments

The reported study was supported by Russian Fund of Fundamental Research (RFBR), research project No. 18-04-00374.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Lewis, D. F. . V. (2001). Guide to cytochromes P450: structure and function. London: Taylor & Francis.Google Scholar
  2. 2.
    Ortiz de Montellano, P. R. (2005). Cytochrome P450: structure, mechanism, and biochemistry. New York: Kluwer Academic/Plenum Publishers.CrossRefGoogle Scholar
  3. 3.
    Hrycay, E. G., & Bandiera, S. M. (2012). The monooxygenase, peroxidase, and peroxygenase properties of cytochrome P450. Archives of Biochemistry and Biophysics, 522, 71–89.CrossRefGoogle Scholar
  4. 4.
    Nebert, D. W., & Russel, D. W. (2002). Clinical importance of the cytochromes P450. The Lancet, 360, 1155–1162.CrossRefGoogle Scholar
  5. 5.
    Guengerich, F. P. (2018). Reference module in biomedical sciences. Comprehensive Toxicology (Third Edition), 10 10.04, 54-86. Cytochrome P450 enzymes.Google Scholar
  6. 6.
    Ferdousi, R., Safdari, R., & Omidi, Y. (2017). Computational prediction of drug-drug interactions based on drugs functional similarities. Journal of Biomedical Informatics, 70, 54–64.CrossRefGoogle Scholar
  7. 7.
    Bezhentsev, V. M., Tarasova, O. A., Dmitriev, A. V., Rudik, A. V., Lagunin, A. A., Filimonov, D. A., & Poroikov, V. V. (2016). Computer prediction of metabolic pathways of xenobiotics in the human body. Successes in Chemistry, 85, 854–879.Google Scholar
  8. 8.
    Tarasova, O., Rudik, A., Dmitriev, A., Lagunin, A., Filimonov, D., & Poroikov, V. (2017). QNA-based prediction of sites of metabolism. Molecules, 22, 2123.CrossRefGoogle Scholar
  9. 9.
    Ashburn, T. T., & Thor, K. B. (2004). Drug repositioning: identifying and developing new uses for existing drugs. Nature Reviews Drug Discovery, 3, 673–683.CrossRefGoogle Scholar
  10. 10.
    Murtazalieva, K. A., Druzhilovskiy, D. S., Goel, R. K., Sastry, G. N., & Poroikov, V. V. (2017). How good are publicly available web services that predict bioactivity profiles for drug repurposing? SAR and QSAR in Environmental Research, 28, 843–862.CrossRefGoogle Scholar
  11. 11.
    Kennedy, C., Brewer, L., & Williams, D. (2016). Drug interactions. Clinical Pharmacology, Medicine, 44(7), 422–426.Google Scholar
  12. 12.
    Carrara, S., Cavallini, A., Erokhin, V., De Micheli, G. (2011). Multi-panel drugs detection in human serum for personalized therapy. Biosensors and Bioelectronics, 26, 3914–3919.Google Scholar
  13. 13.
    Zhang, L., Reynolds, K. S., Zhao, P., & Huang, S.-M. (2010). Drug interactions evaluation: an integrated part of risk assessment of therapeutics. Toxicology and Applied Pharmacology, 243, 134–145.CrossRefGoogle Scholar
  14. 14.
    Kim, H. J., Kim, I. S., Rehman, S. U., Ha, S. K., Nakamura, K., & Yoo, H. H. (2017). Effects of 6-paradol, an unsaturated ketone from gingers, on cytochrome P450-mediated drug metabolism. Bioorganic and Medicinal Chemistry, 27, 1826–1830.CrossRefGoogle Scholar
  15. 15.
    Schneider, E., & Clark, D. S. (2013). Cytochrome P450 (CYP) enzymes and the development of CYP biosensors. Biosensors and Bioelectronics, 39, 1–13.CrossRefGoogle Scholar
  16. 16.
    Shumyantseva, V. V., Shich, E. V., Makhova, A. A., Bulko, T. V., Kukes, V. G., Sizova, O. S., Ramenskaya, G. V., Usanov, S. A., & Archakov, A. I. (2012). The influence of B group vitamins on monooxygenase activity of cytochrome P450 3A4: pharmacokinetics and electro analysis of the catalytic properties. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 6, 87–93.CrossRefGoogle Scholar
  17. 17.
    Makhova, A. A., Shumyantseva, V. V., Shich, E. V., Bulko, T. V., Kukes, V. G., Sizova, O. S., Ramenskaya, G. V., Usanov, S. A., & Archakov, A. I. (2011). Electroanalysis of cytochrome P450 3A4 catalytic properties with nanostructured electrodes: The influence of vitamins B group on diclofenac metabolism. BioNanoScience, 1, 46–52.CrossRefGoogle Scholar
  18. 18.
    Shich, E. V., Fomin, E., Shumyantseva, V. V., & Bulko, T. V. (2012). Combined therapy of elderly patients taking into account the metabolism of drugs. Clinical gerontology, 18, 54–58.Google Scholar
  19. 19.
    Gilep, A. A., Guryev, O. L., Usanov, S. A., & Estabrook, R. W. (2001). Apo-cytochrome b5 as an indicator of changes in heme accessability: preliminary studies with cytochrome P450 3A4. Journal of Inorganic Biochemistry, 87(4), 237–244.CrossRefGoogle Scholar
  20. 20.
    Omura, T., & Sato, R. (1964). The carbon monoxide-binding pigment of liver microsomes I: evidence for its hemoprotein nature. Journal of Biological Chemistry, 239, 2370–2378.Google Scholar
  21. 21.
    Shumyantseva, V. V., Makhova, A. A., Bulko, T. V., Kuzikov, A. V., Shich, E. V., Suprun, E. V., Kukes, V. G., Usanov, S. A., & Archakov, A. I. (2013). The dose-dependent influence of vitamins with antioxidant properties on electrochemically driven cytochromes P450 catalysis. Oxidants and Antioxidants in Medical Science, 2, 113–117.CrossRefGoogle Scholar
  22. 22.
    Smirnov, V. V., Savchenko, A. Y., & Ramenskaya, G. V. (2010). Development and validation of the quantitative determination of endogenous cortisol and 6-β-hydroxycortisol in urine in order to determine the activity of the CYP 3A4 isoenzyme. Biomedicine, 4, 56–60.Google Scholar
  23. 23.
    Fantuzzi, A., Mak, L. H., Capria, E., Dodhia, V., Panicco, P., Collins, S., & Gilardi, G. (2011). A new standardised electrochemical array for drug metabolic profiling with human cytochromes P450. Analytical Chemistry, 83, 3831–3839.CrossRefGoogle Scholar
  24. 24.
    Shumyantseva, V. V., Makhova, A. A., Bulko, T. V., Kuzikov, A. V., Shich, E. V., Kukes, V. G., & Archakov, A. I. (2015). Electrocatalytic cycle of P450 cytochromes: the protective and stimulating roles of antioxidants. RSC Advances, 5, 71306–71313.CrossRefGoogle Scholar
  25. 25.
    Shumyantseva, V. V., Makhova, A. A., Bulko, T. V., Bernhardt, R., Kuzikov, A. V., Shich, E. V., Kukes, V. G., & Archakov, A. I. (2015). Taurine modulates catalytic activity of cytochrome P450 3A4. Biochemistry (Moscow), 80, 366–373.CrossRefGoogle Scholar
  26. 26.
    Polasek, T. M., & Miners, J. O. (2006). Quantitative prediction of macrolide drug-drug interaction potential from in vitro studies using testosterone as the human cytochrome P4503A substrate. European Journal of Clinical Pharmacology, 62, 203–208.CrossRefGoogle Scholar
  27. 27.
    Calabresi, L., Pazzucconi, F., Ferrara, S., Di Paolo, A., Tacca, M. D., Sirtori, C. (2004). Pharmacokinetic interactions between omeprazole/pantoprazole and clarithromycin in health volunteers. Pharmacological Research, 49, 493–499.Google Scholar
  28. 28.
    Shumyantseva, V. V., Bulko, T. V., Suprun, E. V., Kuzikov, A. V., Agafonova, L. E., & Archakov, A. I. (2015). Electrochemical methods for biomedical investigations. Biomedical Chemistry, 61, 188–202.Google Scholar
  29. 29.
    Kuzikov, A. V., Masamrekh, R. A., Khatri, Y., Zavialova, M. G., Bernhardt, R., Archakov, A. I., & Shumyantseva, V. V. (2016). Scrutiny of electrochemically-driven electrocatalysis of C-19 steroid 1α-hydroxylase (CYP260A1) from Sorangium cellulosum So ce56. Analytical Biochemistry, Academic Press, 513, 28–35.CrossRefGoogle Scholar
  30. 30.
    Shumyantseva, V. V., Bulko, T. V., Kuznetsova, G. P., Samenkova, N. F., & Archakov, A. I. (2009). Electrochemistry of cytochromes P450: analysis of current-voltage characteristics of electrodes with immobilized cytochromes P450 for the screening of substrates and inhibitors. Biochemistry (Moscow), 74, 438–444.CrossRefGoogle Scholar
  31. 31.
    Sadeghi, S., Ferrero, S., Di Nardo, G., & Gilardi, G. (2012). Drug–drug interactions and cooperative effects detected in electrochemically driven human cytochrome P450 3A4. Bioelectrochemistry, 86, 87–91.CrossRefGoogle Scholar
  32. 32.
    Yasui, H., Hayashi, S., & Sakurai, H. (2005). Possible involvement of singlet oxygen species as multiple oxidants in P450 catalytic reactions. Drug Metabolism and Pharmacokinetics, 20, 1–13.CrossRefGoogle Scholar
  33. 33.
    Akiyoshi, T., Ito, M., Murase, S., Miyazaki, M., Guengerich, F. P., Nakamura, K., Yamamoto, K., & Ohtani, H. (2013). Mechanism-based inhibition profiles of erythromycin and clarithromycin with cytochrome P450 3A4 genetic variants. Drug Metabolism and Pharmacokinetics, 28, 411–415.Google Scholar
  34. 34.
    Sekiguchi, N., Higashida, A., Kato, M., Nabuchi, Y., Mitsui, T., Takanashi, K., Aso, Y., & Ishigai, M. (2009). Prediction of drug-drug interactions based on time-dependent inhibition from high throughput screening of cytochrome P450 3A4 inhibition. Drug Metabolism and Pharmacokinetics, 24, 500–510.CrossRefGoogle Scholar
  35. 35.
    Berg-Candolfi, M., & Candolfi, E. (1996). Depression of the N-demethylation of erythromycin, azithromycin, clarithromycin and clindamycin in murine toxoplasma infection. International Journal for Parasitology, 26, 1321–1323.CrossRefGoogle Scholar
  36. 36.
    Welsh, O., Vera-Cabrera, L., & Welsh, E. (2010). Onychomycosis Clinics in Dermatology, 28, 151–159.Google Scholar
  37. 37.
    Venkatakrishnan, K., von Moltke, L. L., Greenblatt, D, J. (2000). Effects of the antifungal agents on oxidative drug metabolism. Clinical Pharmacokinetics , 38, 111–180.Google Scholar
  38. 38.
    Krasulova, K., Dvorak, Z., & Anzenbacher, P. (2018). In vitro analysis of itraconazole cis-diastereoisomers inhibition of the nine cytochrome P450 enzymes: stereoselective inhibition of CYP3A. Xenobiotica, 22, 1–7.Google Scholar
  39. 39.
    Baj-Rossi, C., Müller, C., von Mandach, U., De Micheli, G., Carrara, S. (2015) Faradic peaks enhanced by carbon nanotubes in microsomal cytochrome P450 electrodes. Electroanalysis, 27, 1507–1515.Google Scholar
  40. 40.
    Joseph, S., Rusling, J. F., Lvov, Y. M., Friedberg, T., & Fuhr, U. (2003). An amperometric biosensor with human CYP3A4 as a novel drug-screening tool. Biochemical Pharmacology, 65, 1817–1826.CrossRefGoogle Scholar
  41. 41.
    Kuzikov, A. V., Masamreh, R. A., Bulko, T. V., Makhova, A. A., Archakov, A. I., Usanov, S. A., Shich, E. V., & Shumyantseva, V. V. (2016). Analysis of the influence of meldonia on the catalytic activity of cytochrome P450 3A4. Bulletin of the Russian State Medical University, 6, 10–15.CrossRefGoogle Scholar
  42. 42.
    Bogdan, A. N. (2010). Azafen: application in modern clinical practice. Psychiatry and psychopharmacotherapy, 12, 20–23 (in Russian).Google Scholar
  43. 43.
    Otdelenov, V. A., Smirnov, V. V., Dmitriev, A. V., Poryokov, V. V., Shumyantseva, V. V., Krasnykh, L., Sychev, D., Kukes, V. Influence of ethylmethylhydroxypyridine malate on the activity of CYP3A4: an integrated approach to assessing the effect on the biotransformation system of drugs. Medications and rational pharmacotherapy, 3, 30–36 (in Russian).Google Scholar
  44. 44.
    Sizova, O. S., Potekayev, N. N., Zhukovsky, R. O., & Shikh, E. V. (2011). Opportunities for reducing hepatotoxicity of itraconazole in combination with taurine in patients with onychomycosis. Clinical Dermatology and Venerology, 1, 45–49 (in Russian).Google Scholar
  45. 45.
    Kuzikov, A. V., Masamrekh, R. A., Archakov, A. I., Shumyantseva, V. V. (2018) Methods for determination of functional activity of cytochrome P450 isoenzymes, Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 12, 220–240.Google Scholar
  46. 46.
    Letelier, M., Sandoval, J., Berrнos, A.-M., Faundez, M., Aracena-Parks, P., & Aguilera, F. (2010). Melatonin protects the cytochrome P450 system through a novel antioxidant mechanism. Chemico-Biological Interactions, 185, 208–214.CrossRefGoogle Scholar
  47. 47.
    Zhang, Z., & Tang, W. (2018). Drug metabolism in drug discovery and development. Acta Pharmaceutica Sinica B, 8, 721–732.CrossRefGoogle Scholar
  48. 48.
    Shumyantseva, V. V., Masamrekh, R. A., Kuzikov, A. V., & Archakov, A. I. (2018). From electrochemistry to enzyme kinetics of cytochrome P450. Biosensors and Bioelectronics, 21, 192–204.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Victoria V. Shumyantseva
    • 1
    • 2
    Email author
  • Anna A. Makhova
    • 3
  • Evgenia V. Shikh
    • 3
  • Tatiana V. Bulko
    • 1
  • Alexey V. Kuzikov
    • 1
    • 2
  • Rami A. Masamrekh
    • 1
    • 2
  • Tatyana Shkel
    • 4
  • Sergey Usanov
    • 4
  • Andrei Gilep
    • 4
  • Alexander I. Archakov
    • 1
    • 2
  1. 1.Institute of Biomedical ChemistryMoscowRussia
  2. 2.Pirogov Russian National Research Medical UniversityMoscowRussia
  3. 3.Sechenov First Moscow State Medical UniversityMoscowRussia
  4. 4.Institute of Bioorganic Chemistry NASBMinskBelarus

Personalised recommendations