Biotransformation of bisphenol AF to its major glucuronide metabolite reduces estrogenic activity

PloS One
Ming LiBing Shao

Abstract

Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-re...Continue Reading

References

Nov 5, 1997·The New England Journal of Medicine·S H Safe
Apr 4, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·L H PottengerJ M Waechter
Jul 14, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·S YoshiharaS Ohta
Sep 18, 2001·Biological & Pharmaceutical Bulletin·T NiwaM Katagiri
Dec 24, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shin'ichi YoshiharaShigeru Ohta
Jan 7, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shigeyuki KitamuraShigeru Ohta
Nov 18, 2005·Toxicology·Jeong-Hun KangFusao Kondo
Jan 6, 2006·Environmental Health Perspectives·Paloma Alonso-MagdalenaAngel Nadal
Oct 3, 2006·Nature Genetics·Jason S CarrollMyles Brown
Feb 28, 2007·Carbohydrate Research·Carl Johan ArewångAnna-Karin Tidén
Jun 26, 2007·Environmental Health Perspectives·Devra Lee DavisRikuo Doi
Aug 21, 2007·Reproductive Toxicology·Ruth A KeriGail S Prins
Jan 30, 2008·Basic & Clinical Pharmacology & Toxicology·Ana M SotoCarlos Sonnenschein
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·N Ben-Jonathan, R Steinmetz
Oct 23, 2008·Environmental Health Perspectives·Minerva Mercado-Feliciano, Robert M Bigsby
Apr 30, 2010·Environmental Health Perspectives·Ayami MatsushimaYasuyuki Shimohigashi
Jul 27, 2010·Toxicology and Applied Pharmacology·Daniel R DoergeJeffrey W Fisher
Jun 4, 2011·Biology of Reproduction·Kristen Weber Lozada, Ruth A Keri
Aug 9, 2011·Toxicology and Applied Pharmacology·Daniel R DoergeJeffrey W Fisher
Jan 5, 2012·Environmental Health Perspectives·Yipeng SuiChangcheng Zhou
Sep 22, 2012·Neurotoxicity Research·Soyoung LeeSang-Hyun Kim
Mar 9, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jan SchmidtLucija Peterlin Mašič

❮ Previous
Next ❯

Citations

Oct 31, 2016·Environmental Toxicology and Pharmacology·Darja Gramec Skledar, Lucija Peterlin Mašič
Jan 14, 2020·Environmental Science and Pollution Research International·Ajibola A BayodeEmmanuel I Unuabonah
Apr 2, 2021·Environmental Science & Technology·Nan ZhaoHangbiao Jin
Nov 25, 2020·Journal of the American Society for Mass Spectrometry·Ons Ousji, Lekha Sleno
Dec 16, 2017·Environmental Science & Technology·Hangbiao JinZongwei Cai

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
nuclear magnetic resonance
NMR

Related Concepts

Related Feeds

Autoimmune Polyendocrinopathies

Autoimmune polyendocrinopathies, also called polyglandular autoimmune syndromes (PGASs), or polyendocrine autoimmune syndromes(PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. Discover the latest research on autoimmune polyendocrinopathies here.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Autoimmune Polyendocrine Syndromes

This feed focuses on a rare genetic condition called Autoimmune Polyendocrine Syndromes, which are characterized by autoantibodies against multiple endocrine organs. This can lead to Type I Diabetes.