کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5859698 | 1562614 | 2016 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
New brominated flame retardants and their metabolites as activators of the pregnane X receptor
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
CyPPPARTBPHPXRTBBATBBBrominated flame retardants - بازدارنده های شعله برومندCytochrome P450 - سیتوکروم پی۴۵۰Metabolites - متابولیت هاpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازPeroxisome proliferator activated receptor - گیرنده فعال فعال پروکسیومPregnane X receptor - گیرنده پیش گران X
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: New brominated flame retardants and their metabolites as activators of the pregnane X receptor New brominated flame retardants and their metabolites as activators of the pregnane X receptor](/preview/png/5859698.png)
چکیده انگلیسی
The present study investigated the activities on different nuclear receptors of the new brominated flame retardants 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH), and their main carboxylic acid metabolites 2,3,4,5-tetrabromobenzoic acid (TBBA) and mono(2-ethylhexyl) tetrabromophthalate (TBMEPH). None of selected chemicals exhibited marked activity towards PPARα and PPARγ by the use of transactivation assays in HepG2 cells transfected with peroxisome proliferator-activated receptors. In contrast, selected flame retardants all exhibited potent agonist activity on pregnane X receptor (PXR), with EC50 values of 5.5 μM for TBPH and 2.0 μM for its metabolite TBMEPH. Molecular docking of TBPH and TBMEPH to the PXR ligand binding site revealed similar interactions, with differences only for conformation and orientation of the alkyl chains. Additionally, TBPH showed antagonist activity on PXR (IC50, 13.9 μM). Moreover, there was significant up-regulation of CYP3A4 expression via PXR activation for TBB and TBPH and their metabolites. Induction of CYP3A4 might cause undesired drug-drug interactions, lower bioavailability of pharmaceutical drugs, higher formation of reactive toxic metabolites, or enhanced elimination of endogenous hormones, such as T3/T4, to lead to endocrine disruption. These data provide new and important insights into the toxicity of these new polybrominated flame retardants, TBB and TBPH, and their metabolites.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 259, 30 September 2016, Pages 116-123
Journal: Toxicology Letters - Volume 259, 30 September 2016, Pages 116-123
نویسندگان
Darja Gramec Skledar, Tihomir TomaÅ¡iÄ, Adriana Carino, Eleonora Distrutti, Stefano Fiorucci, Lucija Peterlin MaÅ¡iÄ,