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Effect of food supplement mixtures on selected biotransformation enzymes
Kurshakova, Evgeniia ; Dračínská, Helena (advisor) ; Koblihová, Jitka (referee)
Dietary supplements are globally used products designed to complement nutrition with additional nutrients. They contain a wide range of biologically active compounds: amino acids, vitamins, minerals, herbal extracts, etc. Due to the popularity and excessive consumption of food supplements, there is a growing need to research their potential interactions and impact on human health. Certain dietary supplements are metabolized by enzymes from the cytochrome P450 group, which play a key role in the biotransformation of exogenous substrates. Some biologically active compounds may also affect their activity. The presented thesis was focused on studying the influence of several popular components of dietary supplements on cytochromes P450 3A4 and 1A1 expressed in the gastrointestinal tract. The influence of metal ions Zn2+ and Mg2+ , ascorbate from the vitamin group, and curcumin from the polyphenol group was examined. A strong inhibitory effect of curcumin on the activity of both investigated isoforms was confirmed. The reaction of 6β-hydroxylation of testosterone catalyzed by CYP3A4 was significantly suppressed by the addition of curcumin, with the determined IC50 value being 4,7 M. A significant decrease in the rate of resorufin O-deethylation by rat and human CYP1A1 isoforms was also observed (IC50 =...
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Inhibitory effect of endocrine disruptor 17α-ethinylestradiol on cytochrome P450 subfamily 1A
Kurshakova, Evgeniia ; Dračínská, Helena (advisor) ; Ptáčková, Renata (referee)
17-ethinylestradiol (EE2) is a synthetic derivative of the natural estrogen 17-estradiol. It is used in medicine as a key component of oral contraceptives. Due to its ability to modulate the functions of the endocrine system, EE2 belongs to the group of endocrine disruptors. The ability to bioaccumulate and affect the reproduction and development of wildlife makes EE2 a compound that possesses a potential environmental risk. Cytochromes P450 1A1 and 1A2 catalyze the oxidative reactions in metabolism of exogenous compounds, including EE2. 17-Ethinylestradiol is known to have a strong inhibitory effect on the isoform CYP1A1. Within the framework of the present thesis, the inhibition effect of EE2 on the activity of cytochromes P450 of subfamily 1A was studied in vitro via three marker reactions: 7-methoxyresorfin O-demethylation, 7-ethoxyresorufin O-deethylation and phenacetin O-deethylation, which had to be pre-optimised for the following uses. A highly selective inhibitory effect of 17-ethinylestradiol on the human and rat isoform CYP1A1 was confirmed. An inhibitory effect on the activity of the CYP1A2 isoform was not observed by any of marker reactions. Using phenacetin O-deethylation, the concentration of EE2 causing 50% inhibition of CYP1A1 (IC50) was also determined, being of 3,4 M, at a...
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