Novel Pathway of Metabolic Activation of Bisphenol A-Related Compounds for Estrogenic Activity

Okuda, Kunio; Fukuuchi, Tomoko; Takiguchi, Mitsuyoshi; Yoshihara, Shu

doi:10.1124/dmd.111.040121

Cited by 63 publications

(30 citation statements)

References 34 publications

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“…This is possibly due to decreased epithelial thickness ( t ; Figure 4G) in the BPA late exposure group, when the mucous cells make up a higher percentage of a thinner epithelium. The effects of BPA exposure on Muc5B may be due to the binding of the parent molecule or its metabolites to estrogen receptors (Okuda et al 2011). Estrogen (17β-estradiol) is known to induce Muc5B expression in airway epithelial cells (Choi et al 2009) via estrogen receptor-α.…”

Section: Discussionmentioning

confidence: 99%

Fetal Exposure of Rhesus Macaques to Bisphenol A Alters Cellular Development of the Conducting Airway by Changing Epithelial Secretory Product Expression

Winkle¹,

Murphy²,

Boetticher³

et al. 2013

Environ Health Perspect

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Background: Bisphenol A (BPA) exposure early in life results in organizational changes in reproductive organs, but the effect of BPA on conducting airway cellular maturation has not been studied. Late gestation is characterized by active differentiation of secretory cells in the lung epithelium.Objective: We evaluated the hypothesis that BPA exposure disrupts epithelial secretory cell development in the fetal conducting airway of the rhesus macaque.Methods: We exposed animals to BPA during either the second (early term) or the third (late term) trimester. There were four treatment groups: a) sham control early term, b) sham control late term, c) BPA early term (BPA-early), and d) BPA late term (BPA-late). Because cellular maturation occurs nonuniformly in the lung, we defined mRNA and protein expression by airway level using microdissection.Results: BPA exposure of the dam during late term significantly accelerated secretory cell maturation in the proximal airways of the fetus; both Clara cell secretory protein (CCSP) and MUC5AC/5B mRNA and protein expression increased.Conclusions: BPA exposure during late gestation accelerates secretory cell maturation in the proximal conducting airways. We identified a critical window of fetal susceptibility for BPA effects on lung epithelial cell maturation in the third trimester. This is of environmental health importance because increases in airway mucins are hallmarks of a number of childhood lung diseases that may be affected by BPA exposure.

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Section: Discussionmentioning

confidence: 99%

Fetal Exposure of Rhesus Macaques to Bisphenol A Alters Cellular Development of the Conducting Airway by Changing Epithelial Secretory Product Expression

Winkle¹,

Murphy²,

Boetticher³

et al. 2013

Environ Health Perspect

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“…In an in vitro study using murine cells, exposure to BPA at concentrations ranging from 10 −10 to 10 −8 M (approximately 0.023 to 2.3 ng ml -1 ) markedly induced spermatogonial proliferation (Sheng & Zhu 2011). Acute toxicity, genotoxicity and estrogenic activity of BPS, BPB and BPF have been reported (Chen et al 2002;Rivas et al 2002;Okuda et al 2011;Pisapia et al 2012). One study showed that exposure to BPAF considerably reduced testosterone levels in adult male rats (Feng et al 2012).…”

Section: Please Scroll Down For Articlementioning

confidence: 95%

A survey of bisphenol A and other bisphenol analogues in foodstuffs from nine cities in China

Liao

Kannan

2014

Food Additives & Contaminants: Part A

295

112

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Bisphenol A (BPA) is a high-production-volume chemical that is widely used in polycarbonate plastics and epoxy food-can coatings. Following several studies that have reported adverse effects of BPA over the past decade, other bisphenol analogues, such as bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF), and bisphenol B (BPB), have been gradually developed as substitutes for BPA in several applications. Nevertheless, few studies have reported on the occurrence of compounds other than BPA in foodstuffs. In this study, 289 food samples (13 categories: cereals and cereal products, meat and meat products, fish and seafood, eggs, milk and milk products, bean products, fruits, vegetables, cookies/snacks, beverages, cooking oils, condiments, and others), collected from nine cities in China, were analysed for eight bisphenol analogues using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BPA and BPF were found widely in foodstuffs at concentrations ranging from below the limit of quantitation (LOQ) to 299 ng g(-1) (mean = 4.94 ng g(-1)) and from below the LOQ to 623 ng g(-1) (mean = 2.50 ng g(-1)), fresh weight, respectively. The highest total concentrations of bisphenols (∑BPs: sum of eight bisphenols) were found in the category of vegetables that included canned products (mean = 27.0 ng g(-1)), followed by fish and seafood (16.5 ng g(-1)) and beverages (15.6 ng g(-1)). ∑BP concentrations (mean = 2-3 ng g(-1)) in milk and milk products, cooking oils, and eggs were low. Food samples sold in metallic cans contained higher mean ∑BP concentrations (56.9 ng g(-1)) in comparison with those packaged in glass (0.43 ng g(-1)), paper (11.9 ng g(-1)), or plastic (6.40 ng g(-1)). The daily dietary intakes of bisphenols were estimated, based on the mean concentrations measured and daily consumption rates of foods, to be 646 and 664 ng kg(-1) bw day(-1) for men and women, respectively.

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“…BPA can be glucuronided by microsomal UGT2B1, which is an isoform of UDP-glucuronosyltransferase (UGT)1718. It has been suggested that metabolic activation to MBP may occur in the detoxification pathway of BPA when glucuronidation cannot work efficiently, although the MBP metabolic activation may not be significant under usual circumstances19. Previous study has shown that the MBP metabolic activation can occur in the rat fetal livers18.…”

Section: Discussionmentioning

confidence: 99%

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth

Liu

Lee

et al. 2016

Sci Rep

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Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (Kfc), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway.

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Novel Pathway of Metabolic Activation of Bisphenol A-Related Compounds for Estrogenic Activity

Cited by 63 publications

References 34 publications

Fetal Exposure of Rhesus Macaques to Bisphenol A Alters Cellular Development of the Conducting Airway by Changing Epithelial Secretory Product Expression

Fetal Exposure of Rhesus Macaques to Bisphenol A Alters Cellular Development of the Conducting Airway by Changing Epithelial Secretory Product Expression

A survey of bisphenol A and other bisphenol analogues in foodstuffs from nine cities in China

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth

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