Catalytic activation of persulfate by nanoscale zero-valent iron-derived supported boron-doped porous carbon for bisphenol A degradation.

In this study, boron-doped porous carbon materials (BCs) with high surface areas were synthesized employing coffee grounds as carbon source and sodium bicarbonate and boric acid as precursors; afterward, nanoscale zero-valent iron (nZVI) and BCs composites (denoted as nZVI@BCs) were further prepared through reduction of FeSO4 by NaBH4 along with stirring. The performance of the nZVI@BCs for activating persulfate (PS) was evaluated for the degradation of bisphenol A (BPA). In comparison with nZVI@Cs/PS, nZVI@BCs/PS could greatly promote the degradation and mineralization of BPA via both radical and non-radical pathways. On the one hand, electron spin resonance and radical quenching studies represented that •OH, SO4•-, and O2•- were mainly produced in the nZVI@BCs/PS system for BPA degradation. On the other hand, the open circuit voltages of nZVI@BCs and nZVI@Cs in different systems indicated that non-radical pathway still existed in our system. PS could grab the unstable unpaired electron on nZVI@BCs to form a carbon material surface-confined complex ([nZVI@BCs]*) with a high redox potential, then accelerate BPA removal efficiency via direct electron transfer. Furthermore, the performances and mechanisms for BPA degradation were examined by PS activation with nZVI@BC composites at various conditions including dosages of nZVI@BCs, BPA and PS, initially pH value, temperature, common anions, and humid acid. Therefore, this study provides a novel insight for development of high-performance carbon catalysts toward environmental remediation.

UV and pulsed electron beam radiation for effective bisphenol A degradation.

The paper presents the results of studying the efficiency of the bisphenol A transformation in water exposed to ultraviolet radiation and a high-energy-pulse-electron beam (e-beam). It has been shown that in both cases, degradation of dissolved bisphenol A occurs, accompanied by an increase in the absorption coefficient in the wavelength region of more than 300 nm. After exposure, products were recorded that fluoresced in the region of more than λ = 400 nm. The fluorescent transformation product of bisphenol A in water (λ = 425 nm) was maximum formatted after an KrCl excilamp irradiated, and under the action of an e-beam, the accumulation of this product was minimal. Under e-beam radiation (170 keV) the efficiency of bisphenol A (1 mM) removal reached 97%. The data obtained allow us to develop ideas about photolysis and radiolysis in natural water systems when knowledge about targeted and optimal conditions for the degradation of bisphenol A is needed.

Structural insight into the mechanisms and interacting features of endocrine disruptor Bisphenol A and its analogs with human estrogen-related receptor gamma.

Bisphenol A (BPA) is a very important chemical from the commercial perspective. Many useful products are made from it, so its production is increasing day by day. It is widely known that Bisphenol A (BPA) and its analogs are present in the environment and that they enter our body through various routes on a daily basis as we use things made of this chemical in our daily lives. BPA has already been reported to be an endocrine disruptor. Studies have shown that BPA binds strongly to the human estrogen-related receptor gamma (ERRγ) and is an important target of it. This study seeks to understand how it interacts with ERRγ. Molecular docking of BPA and its analogs with ERRγ was performed, and estradiol was taken as a reference. Then, physico-chemical and toxicological analysis of BPA compounds was performed. Subsequently, the dynamic behavior of ERRγ and ERRγ-BPA compound complexes was studied by molecular dynamics simulations over 500 ns, and using this simulated data, their binding energies were again calculated using the MM-PBSA method. We observed that the binding affinity of BPA and its analogs was much higher than that of estradiol, and apart from being toxic, they can be easily absorbed in our body as their physicochemical properties are similar to those of oral medicines. Therefore, this study facilitates the understanding of the structure-activity relationship of ERRγ and BPA compounds and provides information about the key amino acid residues of ERRγ that interact with BPA compounds, which can be helpful to design competitive inhibitors so that we can interrupt the interaction of BPA with ERRγ. In addition, it provides information on BPA and its analogs and will also be helpful in developing new therapeutics.

A novel pencil graphite electrode modified with an iron-based conductive metal-organic framework exhibited good ability in simultaneous sensing bisphenol A and bisphenol S.

Bisphenol A (BPA) and its substitute bisphenol S (BPS) are desirable materials widely used in manufacturing plastic products but can pose carcinogenic risks to humans. A new conductive iron-based metal-organic framework (Fe-HHTP)-modified pencil graphite electrode (PGE) for electrochemically sensing BPA and BPS was prepared and fully characterized by SEM, TEM, FT-IR, XRD, and XPS. Results showed that the optimal conditions for preparing Fe-HHTP/PGE were a pH of 6.5, a Fe-HHTP concentration of 2 mg·mL-1, a deposition potential of 0 V, and a deposition time of 100 s. The Fe-HHTP/PGE prepared under such conditions harbored a significant electrocatalytic activity with a detection limit of 0.8 nM for BPA and 1.7 nM for BPS (S/N = 3). Correspondingly, the electrochemical response current was linearly correlated to BPA and BPS, ranging from 0.01 to 100 µM. Fe-HHTP/PGE also obtained satisfactory recoveries by 93.8-102.1% and 96.0-101.3% for detecting BPA and BPS in plastic food packaging samples. Our work has provided a novel electrochemical tool to simultaneously detect BPA and BPS in food packaging samples and environmental matrixes.

Enhanced inhibition of human and rat aromatase activity by benzene ring substitutions in bisphenol A: QSAR structure-activity relationship and in silico docking analysis.

Bisphenol A (BPA) is a widely used plastic material, but its potential endocrine disrupting effect has restricted its use. The BPA alternatives have raised concerns. This study aimed to compare inhibitory potencies of 11 BPA analogues on human and rat placental aromatase (CYP19A1). The inhibitory potency on human CYP19A1 ranged from bisphenol H (IC50, 0.93 µM) to tetramethyl BPA and tetrabromobisphenol S (ineffective at 100 µM) when compared to BPA (IC50, 73.48 µM). Most of them were mixed/competitive inhibitors and inhibited estradiol production in human BeWo cells. Molecular docking analysis showed all BPA analogues bind to steroid active site or in between steroid and heme of CYP19A1 and form a hydrogen bond with catalytic residue Met374. Pharmacophore analysis showed that there were 4 hydrophobic regions for BPA analogues, with bisphenol H occupying 4 regions. Bivariate correlation analysis showed that LogP (lipophilicity) and LogS (water solubility) of BPA analogues were correlated with their IC50 values. Computerized drug metabolism and pharmacokinetics analysis showed that bisphenol H, tetrabromobisphenol A, and tetrachlorobisphenol A had low solubility, which might explain their weaker inhibition on estradiol production on BeWo cells. In conclusion, BPA analogues mostly can inhibit CYP19A1 and the lipophilicity determines their inhibitory strength.

Hormone effects of eighteen bisphenol analogues and their effects on cellular homeostasis and the typical signal pathways.

Through the transfer chain of surroundings from feed to the farmed-animals and ultimately the corresponding livestock and poultry products, people are exposed to large amounts of bisphenol analogues (BPs), such as rational emissions from manufacturing plants, feed packaging bags and food packaging contact. Some BPs have been reported to show certain toxicological effects, especially, estrogen and endocrine disrupting effect. With the increasing application of BPs, the problem is becoming more and more serious. We systematically studied the hormonal effects of 18 BPs and their effects on cell homeostasis and classical signaling pathways by using classical E-SCREEN assay, fluorescent probes and western blotting. The results confirmed the estrogen-like effect of 13 BPs and 6 BPs obtained high docking scores (Scores < -9.0) for the three receptors simultaneously with the main interactions of hydrophobic, hydrogen and π-stacking of T-type bonds. BPAP regulates cells via apoptosis and steroid signaling pathway by intracellular ROS and mitochondrial followed the caspase pathway. BPE and BPS were involved in the classical NF-κB and Hippo signaling pathways. All data provides scientific basis for the safety risk assessment of endocrine disrupting and cellular homeostasis evaluation of BPs as chronic environmental pollution.

Melatonin and Vitamins as Protectors against the Reproductive Toxicity of Bisphenols: Which Is the Most Effective? A Systematic Review and Meta-Analysis.

Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.

Twelve natural estrogens and ten bisphenol analogues in eight drinking water treatment plants: Analytical method, their occurrence and risk evaluation.

Bisphenol analogues (BPs) and natural estrogens (NEs) as two important groups of endocrine-disrupting compounds (EDCs) in drinking water treatment plants (DWTPs) have been hardly investigated except bisphenol A (BPA) and three major NEs including estrone (E1), 17ß-estradiol (E2) and estriol (E3). In this study, a GC-MS analytical method was firstly established and validated for trace simultaneous determination of ten BPs and twelve NEs in drinking water, which included BPA, bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), bsiphenol F (BPF), bsiphenol P (BPP), bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AF (BPAF), bisphenol AP (BPAP), E1, E2, E3, 17α-estradiol (17α-E2), 2-hydroestrone (2OHE1), 16hydroxyestrone (16α-OHE1), 4-hydroestrone (4OHE1), 2-hydroxyesstradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 17-epiestriol (17epiE3), 16-epiestriol (16epiE3) and 16keto-estraiol (16ketoE2). This investigation showed that eighteen out of twenty-two targeted compounds were detected in drinking source waters of eight DWTPs with concentrations ranging from not detected to 142.8 ng/L. Although the conventional treatment process of DWTP could efficiently remove both BPs and NEs with respective removal efficiencies of 74.1%-90.9% and 74.5%-100%, BPA, BPS, BPE, BPZ, E1, 2OHE1, and 2OHE2 were found in the finished drinking waters. Chlorination could remove part of BPs and NEs, but the efficiency varied greatly with DWTP and the reason was unknown. In the finished drinking waters of eight DWTPs, the highest chemically calculated estrogen equivalence (EEQ) derived from BPs and NEs was up to 6.11 ngE2/L, which was over 22 times that could do harm to zebrafish, indicating a potential risk to human health. Given the fact that many chlorination products of BPs and NEs likely have higher estrogenic activities, the estrogenic effect of BPs and NEs in finished drinking water should be accurately examined urgently with the inclusion of BPs, NEs as well as their main chlorinated by-products. This study shed new light on the occurrence, removal, and potential estrogenic effects of BPs and NEs in DWTPs.

Combined Toxic Effects of BPA and Its Two Analogues BPAP and BPC in a 3D HepG2 Cell Model.

Bisphenol A (BPA) is one of the most commonly used substances in the manufacture of various everyday products. Growing concerns about its hazardous properties, including endocrine disruption and genotoxicity, have led to its gradual replacement by presumably safer analogues in manufacturing plastics. The widespread use of BPA and, more recently, its analogues has increased their residues in the environment. However, our knowledge of their toxicological profiles is limited and their combined effects are unknown. In the present study, we investigated the toxic effects caused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP and BPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed that BPA did not reduce cell viability in HepG2 spheroids after 24-h exposure. In contrast, BPAP and BPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC) decreased cell viability in a dose-dependent manner, but the significant difference was only observed for the combination of BPA/BPC (both at 40 µM). After 96-h exposure, none of the BPs studied affected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cell viability in a dose-dependent manner that was significant for the combination of 4 µM BPA and 4 µM BPAP. None of the BPs and their binary mixtures studied affected the surface area and growth of spheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggered oxidative stress, as measured by the production of reactive oxygen species and malondialdehyde, at both exposure times. Overall, the results suggest that it is important to study the effects of BPs as single compounds. It is even more important to study the effects of combined exposures, as the combined effects may differ from those induced by single compounds.

In vivo and in silico assessments of estrogenic potencies of bisphenol A and its analogs in zebrafish (Danio rerio): Validity of in silico approaches to predict in vivo effects.

This study assessed the estrogen-like potencies of bisphenol A (BPA) and its analogs (BPs) using in vivo and in silico approaches in zebrafish. Zebrafish embryos were exposed to 16 BPs, most of which concentration-dependently induced cytochrome P450 19A1b (CYP19A1b) expression. BPs-induced CYP19A1b expression was suppressed by fulvestrant, a nonselective high affinity antagonist for estrogen receptor (Esr) subtypes. For BPs that concentration-dependently induced CYP19A1b expression, we estimated their 50 % effective concentration (EC50) and relative potencies (REPs) with respect to the potency of BPA for inducing CYP19A1b expression. BP C2, Bis-MP, and BPAF showed lower EC50 than BPA, BPE, and BPF, while BPZ and BPB showed moderate EC50. The REP order of the BPs was BP C2 (26) > Bis-MP (24) > BPAF (21) > BPZ (5.8) > BPB (2.7) > BPE (1.5) > BPF (0.63) > 2,4'-BPF (0.22), indicating that some BPs showed greater estrogenic potencies than BPA in our system. We also constructed in silico homology models of ligand binding domains for zebrafish Esr subtypes, including Esr1, Esr2a, and Esr2b. Molecular docking simulations of ligands with the Esr subtypes revealed the interaction energies of some BPs were lower than that of BPA. The interaction energies showed significant positive correlations with their EC50 values for inducing CYP19A1b expression in vivo. This study showed that some BPA analogs have greater estrogenic potencies than BPA and that in silico simulations of interactions between ligands and Esr subtypes may help predict in vivo estrogenic potencies of untested chemicals.

Risk assessment of bisphenol related compounds in canned convenience foods, olives, olive oil, and canned soft drinks in Turkey.

The presence of Bisphenol A (BPA), Bisphenol A Diglycidyl Ether (BADGE), and their derivatives in seventy-nine samples of food products available in Turkish stores was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Among Bisphenol A and its analogues, BPA was the most detected migrant with 56.97%. Fish products had the highest level of BPA with 0.102 mg/kg although only three fish samples exceeded the Specific Migration Limit (SML) for BPA of 0.05 mg/kg of food. The BPF, BPS, and BPB in all analyzed foods ranged between 0-0.021, 0-0.036, and 0.072 mg/kg, respectively. BADGE derivates, BADGE·2H2O and cyclo-di-BADGE (CdB) were present in 57 and 52 samples with concentrations ranging between 0-0.354, and 0-1.056 mg/kg, respectively. All the analyzed traditional Turkish ready-to-eat meals and fish products were contaminated with BADGE·2H2O and CdB. The overall levels of BADGE and the derivates were below the specific migration limit. CdB was found at higher concentrations in traditional Turkish ready-to-eat meals, up to 1.056 mg/kg. The CdB concentration in most of the samples was above the highest figure with 0.05 mg/kg authorized by the German Federal Institute for Risk Assessment. The predominant chlorinated derivative was BADGE·H2O·HCl which was found in thirty-seven samples in the range of 0.007-0.061 mg/kg.

Optimized fabrication of Cu-doped ZnO/calcined CoFe‒LDH composite for efficient degradation of bisphenol a through synergistic visible-light photocatalysis and persulfate activation: Performance and mechanisms.

A novel magnetically separable Cu/ZnO/CoFe‒CLDH composite, whose synthesis was optimized using the Taguchi approach, was optimally synthesized by hydrothermally coupling Cu-doped ZnO and calcined CoFe-LDH. The synthesized Cu/ZnO/CoFe‒CLDH was applied to construct a synergistic process of integrating visible-light photocatalysis (VPC) with persulfate activation (PSA) and to degrade bisphenol A (BPA). Various characterizations proved that Cu/ZnO/CoFe‒CLDH possessed excellent physicochemical, optoelectronic and magnetic properties, thereby enhancing the catalytic performance. The Cu/ZnO/CoFe‒CLDH composite achieved highly efficient BPA degradation during the synergistic VPC‒PSA process, and its reaction rate constant (0.74 h-1) was 6.17-, 4.11-, and 2.85-fold higher than that of Cu/ZnO, CoFe‒CLDH, and Cu/ZnO/CoFe‒CLDH (VPC only), respectively. Moreover, the effects of the catalyst dosage, initial pollutant concentration, solution pH, persulfate dosage and coexisting ions on BPA degradation were comprehensively investigated. Radical-trapping experiments revealed that the contributions of ·OH, SO4·â€’, ·O2-, and 1O2 involved in BPA degradation. Based on the intermediates identified by LC/MS, the main BPA degradation pathways were determined, the overall trend of which reflects a decreasing ecotoxicity. This study verified the effectiveness of the synergistic VPC‒PSA process with Cu/ZnO/CoFe‒CLDH, which could be used as a new reference for removing organic micropollutants from water.

In silico profiling of endocrine-disrupting potential of bisphenol analogues and their halogenated transformation products.

Due to its endocrine-disrupting properties, bisphenol A (BPA) is being phased out from plastics, thermal paper and epoxy resins, and its replacements are being introduced into the market. Bisphenols are released into the environment, where they can undergo halogenation. Unlike BPA, the endocrine-disrupting potential of BPA analogues and their halogenated transformation products has not been extensively studied. The aim of this study was to evaluate the endocrine-disrupting potential of 18 BPA analogues and their halogenated derivatives by calculating affinities for 14 human nuclear receptors utilizing the Endocrine Disruptome and VirtualToxLab™ in silico tools. Our simulations identified AR, ERs, and GR as the most favorable targets of bisphenols and their derivatives. Several BPA analogues displayed a higher predicted potential for endocrine disruption than BPA. Our models highlighted BPZ and BPPH as the most hazardous in terms of predicted endocrine activities. Halogenation, in general, was predicted to increase the binding affinity of bisphenols for AR, ERß, MR, GR, PPARγ, and TRß. Notably, mono- or 2,2'-di-halogenated bisphenols exhibited the highest potential for endocrine disruption. In vitro corroboration of the obtained results should be the next milestone in evaluating the safety of BPA substitutes and their halogenated transformation products.

System-wide health risk prediction for 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene(MBP), a major active metabolite of environmental pollutant and food contaminant - Bisphenol A.

Human exposure to plastic contaminated foods and environmental micro/nano plastic derived chemicals necessitates system-wide health risk assessment. Hence, current study intend to explore the mode of action (MoA) based adverse outcome pathways of 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), the major active metabolite of bisphenol A (BPA). The computational study employed broad range of target prediction, systems biology tools and molecular docking protocols. Further, validation of MBP targets was done using protein-ligand fluorescence quenching assay, endothelial cell culture and chicken embryo vascular angiogenesis models. Interestingly, the current results illustrate that various physiological signaling pathways (MAPK and VEGF related angiogenesis signaling) and disease progression pathways (hypertension, cancer and endocrine disorders) were enriched as potential targets of MBP. Further, docking studies highlights the possible binding mechanism of MBP with important targets including endothelial nitric oxide synthase (eNOS) and serum albumin (BSA). In addition, the validation studies on MBP-BSA interaction (fluorescence quenching), eNOS derived nitric oxide (NOx) generation in endothelial cells and chicken embryo angiogenesis support the system-wide impacts of MBP with highlights on cardiovascular pathogenesis. Thus, the current observation provides novel insights into the system wide impacts of MBP for the futuristic health risk assessment of plastic derived chemicals.

Adverse (geno)toxic effects of bisphenol A and its analogues in hepatic 3D cell model.

Bisphenol A (BPA) is one of the most widely used and versatile chemical compounds in polymer additives and epoxy resins for manufacturing a range of products for human applications. It is known as endocrine disruptor, however, there is growing evidence that it is genotoxic. Because of its adverse effects, the European Union has restricted its use to protect human health and the environment. As a result, the industry has begun developing BPA analogues, but there are not yet sufficient toxicity data to claim that they are safe. We investigated the adverse toxic effects of BPA and its analogues (BPS, BPAP, BPAF, BPFL, and BPC) with emphasis on their cytotoxic and genotoxic activities after short (24-h) and prolonged (96-h) exposure in in vitro hepatic three-dimensional cell model developed from HepG2 cells. The results showed that BPFL and BPC (formed by an additional ring system) were the most cytotoxic analogues that affected cell viability, spheroid surface area and morphology, cell proliferation, and apoptotic cell death. BPA, BPAP, and BPAF induced DNA double-strand break formation (γH2AX assay), whereas BPAF and BPC increased the percentage of p-H3-positive cells, indicating their aneugenic activity. All BPs induced DNA single-strand break formation (comet assay), with BPAP (≥0.1 µM) being the most effective and BPA and BPC the least effective (≥1 µM) under conditions applied. The results indicate that not all of the analogues studied are safer alternatives to BPA and thus more in-depth research is urgently needed to adequately evaluate the risks of BPA analogues and assess their safety for humans.

Potential toxicity of bisphenol A to α-chymotrypsin and the corresponding mechanisms of their binding.

Bisphenol A (BPA) is an endocrine disruptor widely existing in plastics and resins, which can accumulate in animals and human bodies, posing a potential threat to the physiological and biochemical reactions of human beings or other organisms. α-Chymotrypsin is a kind of proteolytic enzyme existing in humans and animals, which can cause diseases when its activity is excessive. However, there is a lack of research on the mechanism of endocrine disruptors affecting α-chymotrypsin activity. In this study, the interaction between BPA and α-chymotrypsin was proved via multiple spectroscopic approaches, enzyme activity change, isothermal titration calorimetry and molecular docking. Results showed that α-chymotrypsin's polypeptide chains were unfolded, and protein skeletons were loosened with the exposure to BPA. α-Helix content increased and ß-sheet content was decreased. The particle size of the BPA-α-chymotrypsin complex became smaller. Fluorescence sensitization may also be explained by a perturbation of the chromophore Trp 141. The thermodynamic parameters of the binding reaction were measured by isothermal titration calorimetry (ITC), which showed that there was hydrophobic interaction between BPA and α-chymotrypsin, which was consistent with the results of molecular docking. Moreover, BPA may stop near the active center of α-chymotrypsin and interact with the key residues His 57 and Ser 195. The above phenomenon explained the result that the activity of α-chymotrypsin increased to 139% when exposed to high dose BPA (40 µM). Taken together, the effects of BPA on the structure and function of α-chymotrypsin were clarified at the molecular level, which made up the gap in the mechanism of BPA on the proteolytic enzyme, and provided a reliable basis for disease avoidance and prevention.

Detection of Bisphenol A and Four Analogues in Atmospheric Emissions in Petrochemical Complexes Producing Polypropylene in South America.

Because of its toxicity and impacts on the environment and human health, bisphenol A (BPA) has been controlled in numerous industrialized nations, increasing demand for bisphenol analogues (BP) for its replacement. However, the consequences of these chemicals on the environment and the health of persons exposed to their emissions are still being researched. The emissions from polypropylene manufacturing facilities in Colombia and Brazil were evaluated in this study, and the presence of bisphenol A and four BPs was detected among the gaseous compounds released, with total concentrations of BPs (∑BP) between 92 and 1565 ng g-1. As the melt flow index (MFI) of the polymer rises, so does the quantity of volatiles in its matrix that are eliminated during deodorization, indicating that the MFI and the amount of bisphenol released have a directly proportional connection.

Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies.

BPA is a known endocrine-disrupting agent that is capable of binding to the estrogen receptor and has exhibited adverse effects in many laboratory animal and in vitro studies. Moreover, it also been shown to have estrogenic, antiandrogenic, inflammatory, and oxidative properties. The widespread presence of BPA in the environment presents a considerable threat to humans. BPA has been shown to be leached into the human ecosystem, where it is commonly found in food products consumed by humans. Although the concentration is relatively low, its prolonged consumption may cause a variety of deleterious health effects. The liver is an important organ for metabolizing and detoxifying toxic metabolites to protect organisms from potentially toxic chemical insults. BPA that is ingested will be eliminated by the liver. However, it has also induced hepatoxicity and injury via various mechanisms. To find research demonstrating the effects of BPA on kidney, a number of databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched. Thus, this review summarizes the research on the relationship between BPA and its effects on the liver-derived from animals and cellular studies. The underlying mechanism of liver injury caused by BPA is also elucidated.

Inhibition of the angiotensin II type 2 receptor AT2R is a novel therapeutic strategy for glioblastoma.

Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (AT2R) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through AT2R. We repurposed EMA401, an AT2R antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of AT2R-expressing GBM spheroids and blocks their invasiveness and angiogenic capacity. The crystal structure of AT2R bound to EMA401 was determined and revealed the receptor to be in an active-like conformation with helix-VIII blocking G-protein or ß-arrestin recruitment. The architecture and interactions of EMA401 in AT2R differ drastically from complexes of AT2R with other relevant compounds. To enhance central nervous system (CNS) penetration of EMA401, we exploited the crystal structure to design an angiopep-2-tethered EMA401 derivative, A3E. A3E exhibited enhanced CNS penetration, leading to reduced tumor volume, inhibition of proliferation, and increased levels of apoptosis in an orthotopic xenograft model of GBM.

The alternative analog plasticizer BPS displays similar phenotypic and metabolomic responses to BPA in HepG2 and INS-1E cells.

Bisphenols A (BPA) and S (BPS) are endocrine-disrupting chemicals that affect energy metabolism, leading to impairment of glucose and lipid homeostasis. We aimed at identifying metabolic pathways regulated by both compounds in human liver cells and rat pancreatic ß-cells that could impair energy homeostasis regulation. We assessed the effects on growth, proliferation, and viability of hepatocarcinoma (HepG2) and insulinoma (INS-1E) cells exposed to either BPA or BPS in a full range concentration between 0.001 and 100 µM. Both the dose and duration of exposure caused a differential response on growth and viability of both cells. Effects were more pronounced on HepG2, as these cells exhibited non-linear dose-responses following exposure to xenobiotics. For INS-1E, effect was observed only at the highest concentration. In addition, we profiled their intracellular state by untargeted metabolomics at 24, 48, and 72 h of exposure. This analysis revealed time- and dose-dependently molecular changes for HepG2 and INS-1E that were similar between BPA and BPS. Both increased levels of inflammatory mediators, such as metabolites pertaining to linolenic and linoleic acid metabolic pathway. In summary, this study shows that BPS also disrupts molecular functions in cells that regulate energy homeostasis, displaying similar but less pronounced responses than BPA.