A study on 17alpha-ethinylestradiol metabolism in rat and Pleurotus ostreatus

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F15%3A00472802" target="_blank" >RIV/61388971:_____/15:00472802 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/15:10313396

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

A study on 17alpha-ethinylestradiol metabolism in rat and Pleurotus ostreatus

Popis výsledku v původním jazyce

OBJECTIVES: 17 alpha-Ethinylestradiol (EE2) is an endocrine disruptor that is an ingredient of oral contraceptives. Here, EE2 metabolism catalyzed by cytochromes P450 (CYP) was studied. Two model organisms, rat and ligninolytic fungus Pleurotus ostreatus, were used. nMETHODS: To resolve the role of rat and/or fungal CYPs in EE2 oxidation, microsomes were incubated with EE2 and NADPH or cumene hydroperoxide. Using Supersomes T, we examined which of rat CYPs oxidize EE2. nRESULTS: EE2 is effectively degraded by P. ostreatus in vivo. In vitro, EE2 is metabolized by CYPs by the NADPH-dependent and organic hydroperoxide-dependent mechanisms. Rat hepatic microsomes metabolize EE2 in the presence of NADPH to three products; two of them are hydroxylated EE2 derivatives. Using rat Supersomes T we found that EE2 is hydroxylated by several rat CYPs, among them CYP2C6 and 2C11 are most efficient in 2-hydroxy-EE2 formation, while CYP2A and 3A catalyze EE2 hydroxylation to the second product. On the contrary, the products of the NADPH-dependent hydroxylating reactions were not detected in Pleurotus ostreatus. During the reaction of EE2 in microsomes isolated from rat and P. ostreatus in the presence of the alternate oxidant, cumene hydroperoxide, another metabolite, different from the above mentioned products, is generated. Rat CYP1A1 is the most efficient enzyme catalyzing formation of this EE2 product. nCONCLUSION: The results suggest that CYPs play a role in EE2 metabolism in rat and P. ostreatus. To our knowledge this is the first finding describing ligninolythic fungal metabolism of EE2 by CYP in the presence of cumene hydroperoxide.

Název v anglickém jazyce

A study on 17alpha-ethinylestradiol metabolism in rat and Pleurotus ostreatus

Popis výsledku anglicky

OBJECTIVES: 17 alpha-Ethinylestradiol (EE2) is an endocrine disruptor that is an ingredient of oral contraceptives. Here, EE2 metabolism catalyzed by cytochromes P450 (CYP) was studied. Two model organisms, rat and ligninolytic fungus Pleurotus ostreatus, were used. nMETHODS: To resolve the role of rat and/or fungal CYPs in EE2 oxidation, microsomes were incubated with EE2 and NADPH or cumene hydroperoxide. Using Supersomes T, we examined which of rat CYPs oxidize EE2. nRESULTS: EE2 is effectively degraded by P. ostreatus in vivo. In vitro, EE2 is metabolized by CYPs by the NADPH-dependent and organic hydroperoxide-dependent mechanisms. Rat hepatic microsomes metabolize EE2 in the presence of NADPH to three products; two of them are hydroxylated EE2 derivatives. Using rat Supersomes T we found that EE2 is hydroxylated by several rat CYPs, among them CYP2C6 and 2C11 are most efficient in 2-hydroxy-EE2 formation, while CYP2A and 3A catalyze EE2 hydroxylation to the second product. On the contrary, the products of the NADPH-dependent hydroxylating reactions were not detected in Pleurotus ostreatus. During the reaction of EE2 in microsomes isolated from rat and P. ostreatus in the presence of the alternate oxidant, cumene hydroperoxide, another metabolite, different from the above mentioned products, is generated. Rat CYP1A1 is the most efficient enzyme catalyzing formation of this EE2 product. nCONCLUSION: The results suggest that CYPs play a role in EE2 metabolism in rat and P. ostreatus. To our knowledge this is the first finding describing ligninolythic fungal metabolism of EE2 by CYP in the presence of cumene hydroperoxide.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EE - Mikrobiologie, virologie

OECD FORD obor

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Projekt

<a href="/cs/project/GA15-02328S" target="_blank" >GA15-02328S: Organismy a mechanismy určující osud endokrinních disruptorů v životním prostředí</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neuroendocrinology Letters

ISSN

0172-780X

e-ISSN

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Svazek periodika

36

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

SE - Švédské království

Počet stran výsledku

8

Strana od-do

5-12

Kód UT WoS článku

000369404400001

EID výsledku v databázi Scopus

2-s2.0-84959320201