No effect of lipoic acid on catalytic activity of cytochrome P450 3A4
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Anna A. Makhova
Abstract
Objectives
α-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 of α-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 of α-lipoic acid on the catalysis of cytochrome P450 3A4. These results can be projected on the possibility of using α-lipoic acid in complex therapy without negative impact on the enzymatic cytochrome P450 system.
Methods
The 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.
Results
It 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−1 and in the presence of LA corresponds to 3.5 ± 0.9 min−1.
Conclusions
Based on the obtained experimental data, we can conclude that there is no significant effect of α-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.
Funding source: Russian Foundation for Basic Research
Award Identifier / Grant number: Project No. 18-04-00374
Research funding: This work was financially supported by the Russian Foundation for Basic Research (Project No. 18-04-00374).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
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Articles in the same Issue
- Editorial
- Clinical implementation of pharmacogenetics and personalized drug prescription based on e-health: the MedeA initiative
- Review
- Pain pharmacogenetics
- Herbal preparations in the management of hypothyroidism in Unani medicine
- Mini Review
- Dapsone for Pneumocystis jirovecii pneumonia prophylaxis – applying theory to clinical practice with a focus on drug interactions
- Original Articles
- No effect of lipoic acid on catalytic activity of cytochrome P450 3A4
- Exploring the potential of pyrazoline containing molecules as Aβ aggregation inhibitors in Alzheimer’s disease
- Potential drug-drug interactions in ICU patients: a retrospective study
- Drug–drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation
- Silver sulfadiazine loaded breathable hydrogel sponge for wound healing
- Protective effect of Cyperus esculentus (tiger nut) extract against scopolamine-induced memory loss and oxidative stress in mouse brain
- Role of purinergic signaling pathways in the adaptogenic-like activity of methyl jasmonate in rats exposed to unpredictable chronic mild stress
