Exposure of rats to exogenous endocrine disruptors 17alpha-ethinylestradiol and benzo(a) pyrene and an estrogenic hormone estradiol induces expression of cytochromes P450 involved in their metabolism

0481476 - MBÚ 2018 RIV SE eng J - Článek v odborném periodiku
Bořek-Dohalská, L. - Klusoňová, Z. - Holecová, J. - Martinková, M. - Bárta, F. - Dračínská, H. - Cajthaml, Tomáš - Stiborová, M.
Exposure of rats to exogenous endocrine disruptors 17alpha-ethinylestradiol and benzo(a) pyrene and an estrogenic hormone estradiol induces expression of cytochromes P450 involved in their metabolism.
Neuroendocrinology Letters. Roč. 37, Sup 1 (2016), s. 84-94. ISSN 0172-780X. E-ISSN 2354-4716
Grant CEP: GA ČR(CZ) GA15-02328S
Institucionální podpora: RVO:61388971
Klíčová slova: endocrine disruptor * 17 alpha-ethinylestradiol * cytochrome P450
Obor OECD: Microbiology
Impakt faktor: 0.918, rok: 2016

OBJECTIVES: The term 'endocrine disruptor' (ED) is used for compounds that mimic or antagonize the effects of endogenous hormones. Synthetic estrogen 17 alpha-ethinylestradiol (EE2) and a human carcinogen benzo[a] pyrene (BaP) are assigned as exogenous endocrine disruptors and an estrogenic hormone estradiol is a natural endogenous disruptor. Here, the potency of these three disruptors administered to rats individually and in combination to induce expression of cytochrome P450 (CYP) enzymes involved in their own metabolism (CYP1A1, 2C and 3A) in vivo was investigated.
METHODS: Changes in CYP protein expression after exposure of rats to BaP, EE2 or estradiol were analyzed by Western blotting. Using the HPLC method, CYP1A1, 2C and 3A specific activities in hepatic microsomes isolated from exposed rats were analyzed.
RESULTS: Whereas exposure to BaP induces expression of CYP1A1 protein and its marker activity (Sudan I oxidation) in liver, kidney and lung of rats, no significant induction of this CYP and its enzyme activity was produced by EE2 and estradiol. Treatment of BaP in combination with EE2 and/or estradiol decreased the BaP-mediated CYP1A1 induction in liver of exposed rats. BaP also induces CYP2C11 protein in rat liver and kidney, but does not increase its enzyme activity measured as testosterone 16 alpha-hydroxylation. The enzyme activity of another enzyme of the 2C subfamily, CYP2C6, diclofenac 4'-hydroxylation, is even decreased by BaP. The CYP2C11 protein expression and/or its activity are also increased in liver of rats treated with EE2 and estradiol, but its expression is significantly decreased in lung. The CYP2C6 activity is also elevated by treatment of rats with EE2 and estradiol administered individually as well as in their combination.
Trvalý link: http://hdl.handle.net/11104/0277031