Affiliation:
1. Sechenov First Moscow State Medical University, Moscow, Russian Federation
2. Institute of Biomedical Chemistry, Moscow, Russian Federation
3. Institute of Bioorganic Chemistry, Minsk, Belarus
4. Pirogov Russian National Research Medical University, Moscow, Russian Federation
Abstract
AbstractObjectivesα-Lipoic acid is used as an antioxidant in multivitamin formulations to restore the normal level of intracellular glutathione after depletion caused by environmental pollutants or during physiological aging of the body, as a chelating agent, as a dietary supplement, in anti-aging compositions. Lipoic acid (LA) acts as a buffer in cancer therapy and in therapy of diseases associated with oxidative stress. The effect of LA on the catalytic functions of cytochrome P450 3A4 as the main enzyme of the biotransformation of drugs was studied. It was shown that LA in the concentration range of 50–200 μM affects the stage of electron transfer (stage of cytochrome P450 3A4 heme reduction), decreasing the cathodic reduction current by an average of 20 ± 5%. The kinetic parameters (kcat) of the N-demethylation reaction of erythromycin, the antibiotic of the macrolide group, used as a marker substrate for the comparative analysis of the catalytic activity of cytochrome P450 3A4, both in the presence ofα-lipoic acid and in the cytochrome P450 3A4-erythromycin complex, amounted to comparable values of 3.5 ± 0.9 and 3.4 ± 0.9 min−1, respectively. Based on these experimental data, we can conclude that there is no significant effect ofα-lipoic acid on the catalysis of cytochrome P450 3A4. These results can be projected on the possibility of usingα-lipoic acid in complex therapy without negative impact on the enzymatic cytochrome P450 system.MethodsThe analysis was performed in electrochemical non-invasive model systems for recording the catalytic activity of cytochrome P450 3A4, using screen-printed electrodes, modified with membranous didodecyldimethylammonium bromide.ResultsIt was shown that LA did not affect the N-demethylation of macrolide antibiotic erythromycin. Catalytic constant (kcat) of N-demethylation of erythromycin corresponds to 3.4 ± 0.9 min−1and in the presence of LA corresponds to 3.5 ± 0.9 min−1.ConclusionsBased on the obtained experimental data, we can conclude that there is no significant effect ofα-lipoic acid on individual stages and processes of catalysis of cytochrome P450 3A4. LA can be recommended for inclusion in complex therapy as an antioxidant, antitoxic and chelating compound without negative impact on the enzymatic cytochrome P450 3A4 activity of the human body.
Funder
Russian Foundation for Basic Research
Subject
Pharmacology (medical),General Pharmacology, Toxicology and Pharmaceutics
Reference62 articles.
1. In vitro interactions of abiraterone, erythromycin, and CYP3A4: implications for drug-drug interactions;Fundamen Clin Pharmacol,2020
2. Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology;J Inorg Biochem,2019
3. The relationships between cytochromes P450 and H2O2: production, reaction, and inhibition;J Inorg Biochem,2018
4. In vitro interactions of abiraterone, erythromycin, and CYP3A4: implications for drug-drug interactions;Fundamen Clin Pharmacol,2020
5. From electrochemistry to enzyme kinetics of cytochrome P450;Biosens Bioelectron,2018
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