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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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