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

Result code in 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>

Alternative codes found

RIV/00216208:11310/15:10313396

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EE - Microbiology, virology

OECD FORD branch

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Project

<a href="/en/project/GA15-02328S" target="_blank" >GA15-02328S: Organisms and mechanisms determining the fate of endocrine disruptors in the environment</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

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

Name of the periodical

Neuroendocrinology Letters

ISSN

0172-780X

e-ISSN

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Volume of the periodical

36

Issue of the periodical within the volume

1

Country of publishing house

SE - SWEDEN

Number of pages

8

Pages from-to

5-12

UT code for WoS article

000369404400001

EID of the result in the Scopus database

2-s2.0-84959320201