当前位置： SCI文献检索 > TOXICOLOGY期刊下所有文献 > Technical pentabromodiphenyl ether and hexabromocyclododecane as activators of the pregnane-X-receptor (PXR).

Technical pentabromodiphenyl ether and hexabromocyclododecane as activators of the pregnane-X-receptor (PXR).

Abstract：

:Technical pentabrominated diphenyl ether (pentaBDE mix) is a mixture of polybrominated diphenyl ethers (PBDEs) which has been widely used as a flame retardant. Since its ban in several countries it has been replaced by other brominated flame retardants such as hexabromocyclododecane (HBCD). Both certain PBDE congeners and HBCD are present in environmental and human samples reflecting their persistent and bioaccumulative properties. PentaBDE mix and HBCD have recently been found to induce cytochrome P450 (CYP) 3 enzymes in rat liver. In this study we tested both technical pentaBDE mix and HBCD for their potency to induce CYP3A enzymes in rat hepatocytes in primary culture, and in rat H4IIE and human HepG2 hepatoma cells. In rat hepatocytes, HBCD was a more effective CYP3A1 inducer than pentaBDE mix, being less effective, however, than the prototype inducer dexamethasone. In human HepG2 cells, both compounds and the prototype inducer rifampicin were about equally effective. In contrast, in HepG2 cells, HBCD failed to induce luciferin-PFBE dealkylase, a common catalytic activity of a number of CYP3A enzymes, possibly reflecting enzyme inhibition. A significant induction of catalytic activity was observed in rat hepatocytes with both compounds. Analysis of a XREM-driven reporter gene activity in transfected cells confirmed that both compounds act as agonists of the human and rat pregnane-X-receptor, which was detectable in all cell types used.

journal_name

Toxicology

journal_title

Toxicology

authors

Fery Y,Buschauer I,Salzig C,Lang P,Schrenk D

doi

10.1016/j.tox.2009.07.009

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

45-51

issue

1-2

eissn

0300-483X

issn

1879-3185

pii

S0300-483X(09)00366-7

journal_volume

264

pub_type

杂志文章

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