Mechanism Of Bisphenol A Research Articles

Bisphenol-A Abrogates Proliferation and Differentiation of C2C12 Mouse Myoblasts via Downregulation of Phospho-P65 NF-κB Signaling Pathway.

Previous studies showed that bisphenol-A (BPA), a monomer of polycarbonate plastic, is leached out and contaminated in foods and beverages. This study aimed to investigate the effects of BPA on the myogenesis of adult muscle stem cells. C2C12 myoblasts were treated with BPA in both proliferation and differentiation conditions. Cytotoxicity, cell proliferation and differentiation, antioxidant activity, apoptosis, myogenic regulatory factors (MRFs) gene expression, and mechanism of BPA on myogenesis were examined. C2C12 myoblasts exposed to 25-50 µM BPA showed abnormal morphology, expressing numerous and long cytoplasmic extensions. Cell proliferation was inhibited and was accumulated in subG1 and S phases of the cell cycle, subsequently leading to apoptosis confirmed by nuclear condensation and the expression of apoptosis markers, cleaved caspase-9 and caspase-3. In addition, the activity of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase was significantly decreased. Meanwhile, BPA suppressed myoblast differentiation by decreasing the number and size of multinucleated myotubes via the modulation of MRF gene expression. Moreover, BPA significantly inhibited the phosphorylation of P65 NF-κB in both proliferation and differentiation conditions. Altogether, the results revealed the adverse effects of BPA on myogenesis leading to abnormal growth and development via the inhibition of phospho-P65 NF-κB.

Fabrication of Ti3+/N/B-TiO2@NGQDs composite photocatalyst with significantly enhanced visible light catalytic activity

A two-step hydrothermal process was used to successfully create Ti3+, N, and B co-doped TiO2 modified with nitrogen doped graphene quantum dots (Ti3+/N/B-TiO2@NGQDs (TNBTN)) composite photocatalyst for photodegradation of bisphenol A (BPA) and methyl orange (MO) under visible-light illumination. The prepared TNBTN composite demonstrated significantly enhanced visible light catalytic performance. Especially, the apparent rate constant of BPA degradation with TNBTN was approximately 56.9 times that of pure TiO2, which was attributed to broader visible light absorbance and faster transmission and separation of photoinduced charge. In addition, the mechanism of BPA and MO degradation with TNBTN was distinct.

Increased levels of IL-17 and autoantibodies following Bisphenol A exposure were associated with activation of PI3K/AKT/mTOR pathway and abnormal autophagy in MRL/lpr mice

Bisphenol A (BPA) is a common environmental endocrine disruptor which mimic the effect of estrogen. The immunotoxicity of BPA has attracted widespread attention in recent years. However, the effects and mechanism of BPA on autoimmune disease were rarely reported. Systemic lupus erythematosus (SLE) is a typical autoimmune disease, and its etiology and mechanism are complex and unclear. Currently, inflammation and the production of autoantibodies are considered to be important pathological mechanisms of SLE, and estrogen contributes to the occurrence and development of SLE. Therefore, in order to explore whether BPA exposure can affect the development of SLE and its possible mechanism, we used MRL/lpr (lupus-prone mice) and C57/BL6 female mice exposed to 0.1 and 0.2 µg/mL BPA for 6 weeks. We discovered that BPA exposure increased the concentration of serum anti-dsDNA antibody and IL-17, and the level of RORγt protein (the transcription factor of Th17 cells). Moreover, there were higher expression of p-PI3K, p-AKT, p-mTOR, ULK, Rubicon, P62, Becline1 and LC3 protein in spleen tissue of BPA exposed MRL/lpr mice compared with the control. However, there were no significant changes in the expression of IL-17, RORγt or mTOR in C57 mice exposed to BPA at the same dose. Our study implied that BPA exposure induced the development of SLE, which might be related to the up-regulation of PI3K/AKT/mTOR signaling pathway and abnormal autophagy. Our study indicated that lupus mice were more susceptible to BPA, and provided a new insight into the mechanism by which BPA exacerbated SLE. Therefore, our study suggested that autoimmune patients and susceptible population should be considered when setting thresholds for environmental BPA exposure.

Bisphenol A adsorption and transport in loess and cationic surfactant/hydrophilic polymer modified bentonite liners

Bisphenol A (BPA) is a toxic endocrine disruptor often found in landfill leachate. Adsorption behaviors and mechanisms of BPA onto organo-bentonites amended loess, e.g., Hexadecyltrimethylammonium chloride-bentonite (HTMAC-B) and Carboxymethylcellulose-bentonite (CMC-B) were experimentally investigated. The adsorption capacity of loess amended by HTMAC-B (LHB) and CMC-B (LCB) is 4.2 and 4 times greater than that of loess (L), respectively. It is attributed to the increase of hydrogen bonds and hydrophobic lateral interactions between the adsorbent and the adsorbate. The binary (Pb2+-BPA) systems may enhance BPA adsorption onto the samples by the formation of coordination bonds between the hydroxyl group of BPA and Pb2+ ions. A cycled column test was used for investigating the transport behavior of BPA in LHB and LCB samples. The hydraulic conductivity of loess amended by the organo-bentonite (e.g., HTMAC-B, CMC-B) is generally lower than 1 × 10−9 m/s. Especially for CMC-B amended loess, the hydraulic conductivity can be reduced to 1 × 10−12 m/s. This guarantees the hydraulic performance of the liner system. Transport behavior of BPA in cycled column test is explained by the mobile-immobile model (MIM). Modelling results showed that loess amended by organo-bentonites can increase the breakthrough time of BPA. In comparison to loess-based liner, the breakthrough time of BPA for LHB and LCB can be increased by a factor of 10.4 and 7.5, respectively. These results indicate that organo-bentonites can serve as a potentially effective amendment for improving the adsorption of loess-based liners.

Abnormal histone replacement following BPA exposure affects spermatogenesis and fertility sequentially

Bisphenol A (BPA) is an endocrine-disrupting chemical widely distributed in the environment. Its exposure has been linked to male infertility in animals and humans due to its ability to induce epigenetic modification. Despite extensive research confirming the impact of BPA on epigenetic regulation, fundamental concerns about how BPA causes epigenetic changes and the underlying mechanism of BPA on the male reproductive system remain unresolved. Therefore, we sought to investigate the effects of BPA on epigenetic regulation and the histone-to-protamine (PRM) transition, which is fundamental process for male fertility in testes and spermatozoa by exposing male mice to BPA for 6 weeks while giving the mice in the control group corn oil by oral gavage. Our results demonstrated that the mRNA levels of the histone family and PRMs were significantly altered by BPA exposure in testes and spermatozoa. Subsequently, core histone proteins, the PRM1/PRM2 ratio, directly linked to male fertility, and transition proteins were significantly reduced. Furthermore, we discovered that BPA significantly caused abnormal histone-to-protamine replacement during spermiogenesis by increased histone variants-related to histone-to-PRM transition. The levels of histone H3 modification in the testes and DNA methylation in spermatozoa were significantly increased. Consequently, sperm concentration/motility/hyperactivation, fertilization, and early embryonic development were adversely affected as a consequence of altered signaling proteins following BPA exposure. To our knowledge, this is the first study to indicate that BPA exposure influences the histone-to-PRM transition via altering epigenetic modification and eventually causing reduced male fertility.

Bisphenol A and 17α-Ethinylestradiol Removal from Water by Hydrophobic Modified Acicular Mullite

The hydrophilicity and hydrophobicity of adsorbents have an important influence on organic pollutants adsorption. To effectively remove bisphenol A (BPA) and 17-acetylene estradiol (EE2) from water, acicular mullite was modified by cetyl trimethyl ammonium bromide (CTMAB) to increase the hydrophobicity of the mullite. The adsorption process and mechanism of BPA and EE2 by modified acicular mullite were studied in detail. Results indicated that the concentration of CTMAB solution was related to the contact angle of CTMAB-modified mullite (CTMAB-M). The optimal concentration of CTMAB was 4 mmol/L. The CTMAB-M could adsorb more hydrophobic organic pollutants than virgin acicular mullite. Due to the electrostatic attraction and hydrophobic partitioning, the adsorption amount of BPA and EE2 on CTMAB-M increased with increasing pH. The adsorption amounts of BPA and EE2 on CTMAB-M increase with increasing ionic strength. The adsorption kinetics of BPA and EE2 adsorption on CTMAB-M could be best described by the pseudo second-order kinetics model. Thermodynamic analysis showed that the low temperature favored the adsorption of BPA and EE2 on CTMAB-M, and the adsorption was driven by entropy increase. Site energy studies indicated that BPA and EE2 firstly occupy high-energy adsorption sites and then switch to low-energy sites during the adsorption process. The average adsorption site energy μ(E*) of EE2 on CTMAB-M is smaller than BPA. CTMAB modification can significantly improve the removal efficiency of ceramsite on EDCs.

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 β-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.

Bisphenol A reveals its obesogenic effects through disrupting glucose tolerance, oxidant-antioxidant balance, and modulating inflammatory cytokines and fibroblast growth factor in zebrafish.

Obesogens affect lipid metabolism, and genetic or epigenetic factors may also contribute to the progression of obesity. Endocrine-disrupting chemicals (EDCs) are the most striking among obesogens. Bisphenol A (BPA) is an estrogenic EDC used in food containers, adhesives, dye powders, and dental fillers. We aimed to elucidate molecular mechanisms of BPA's obesogenic effects focusing on obesogenic pathways in the liver including fibroblast growth factor (FGF) and Dnmt3a which is its epigenetic regulator, oxidant-antioxidant status, and inflammatory cytokines. Zebrafish were divided into three groups as control, low-dose BPA (1μm BPA), and high-dose BPA groups (10μm BPA). At the end of 30days, oral glucose tolerance test (OGTT) was performed, fasting blood glucose levels were measured, and hepatopancreas tissues were taken. Malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione S-transferase (GST), and nitric oxide (NO) activities were examined in the hepatopancreas. Inflammatory cytokines, lepa, fgf21, and dnmt3a expressions were determined by RT-PCR. BPA exposure increased the body weights, il1ß, tnfα, il6, lepa, fgf21, and dnmt3a expressions, impaired glucose tolerance, and oxidant-antioxidant status in a dose-dependent manner. Hepatocyte degeneration, lipid vacuolization, and vasocongestion were observed in both BPA-exposed groups. Our study suggests impaired glucose tolerance, oxidant-antioxidant balance, increased inflammatory response, fgf21 expression, and dnmt3a expressions as the possible mechanisms for the BPA-induced obesity model in zebrafish.

Bisphenol A disrupts apolipoprotein E expression through estrogen-related receptor gamma and DNA methlylation in the liver of male rare minnow Gobiocypris rarus

An increasing number of studies show that bisphenol A (BPA) can cause lipid metabolism disorder. However, few studies focused on the effect of BPA on lipid transport. Apolipoprotein E (ApoE) plays important roles in triglyceride (TG) transportation. Our previous study found that ApoE was a sensitive gene in response to BPA exposure in male rare minnow. To investigate the effect and mechanism of BPA on hepatic ApoE, adult male rare minnow Gobiocypris rarus were exposed to environmentally relevant concentrations of BPA (15 μg/L) for 1, 3 and 5 weeks. Results showed that BPA inhibited ApoE expression at week 1 and 5, while induced its expression at week 3. A positive estrogen-related receptor gamma (Esrrg) response element was identified in the promoter region of ApoE. The change of the Esrrg recruitment was consistent with ApoE mRNA expression. Moreover, the methylation status of the CpG sites near and on the Esrrg binding sites changed opposite to the ApoE mRNA level, which may be the main cause for the change in Esrrg recruitment. The expression of ApoE protein was significantly enhanced following long-term BPA exposure. Consistently, the TG accumulation was significantly increased in the plasma. The present study demonstrates that BPA could affect rare minnow ApoE expression, which is probably one of the ways for BPA disturbing fish lipid metabolism.

Bisphenol A drives di(2-ethylhexyl) phthalate promoting thyroid tumorigenesis via regulating HDAC6/PTEN and c-MYC signaling

Bisphenol A (BPA) and di-(2-ethylhcxyl) phthalate (DEHP) are exist widespread in the environment and produce adverse effect to human as environmental disruptors (EDCs). Epidemiological studies have found that the exposure of DEHP and BPA could increase the susceptibility to thyroid diseases including thyroid cancer and benign thyroid nodules. Due to the existence of multiple pollutants in our daily life, the mixed toxic effects of exposure and their interrelationships may distinguish from the exposure to a single chemical, so it is of great significance to explore the mixed toxic effect of DEHP and BPA co-exposure. Thyroid, as one of the target organs of EDCs, is prone to tumor occurrence, however, whether the mixture of BPA and DEHP will affect the occurrence of thyroid cancer is still obscure. We aim to investigate the effect of single or combined exposure to BPA and DEHP on the occurrence of thyroid cancer. An animal model of exposure to BPA and DEHP was firstly established to evaluate their effect on DMD-induced thyroid cancer. Additionally, human thyroid cancer cells BCPAP and thyroid cells Nthy-ori3–1 were used to further clarify some possible mechanisms of BPA and MEHP, the main metabolite of DEHP. Consequently, we found that BPA alone could increase the incidence of thyroid tumors in female rats compared with DEHP, and DEHP enhanced the effect of BPA on cancer promotion. BPA alone and in combination with DEHP mainly induced the expression of HDAC6, inhibited tumor suppressor gene PTEN upregulated the expression of oncogene c-MYC, and eventually elevate the susceptibility to thyroid tumors. Mechanistically, BPA alone and in combination with MEHP could significantly induce the proliferation of BCPAP cells depending on HDAC6, which could modulate H3K9ac to inhibit PTEN, activate AKT signaling pathway, and simultaneously upregulate the expression of c-MYC. Interestingly, we found that BPA alone and in combination with MEHP could significantly induce the proliferation of Nthy-ori3–1 cells independent on HDAC6 via activating ERK signaling pathway. Taken together, these findings not only provide new evidence of the promoting effect of BPA and DEHP on thyroid cancer but also discusses some possible mechanisms underlying these effects.

Systems toxicology approach explores target-pathway relationship and adverse health impacts of ubiquitous environmental pollutant bisphenol A

ABSTRACT The effects of environmental chemicals on health outcomes may be underestimated due to deficiency of knowledge regarding the actions of compounds on toxico-pathogenic mechanisms underlying biological systems outcomes. In this regard, the current study aimed to explore the potential target-pathway-disease relationship attributed to bisphenol A (BPA) responses in target tissues. Computational methods including reverse pharmacophore mapping approach, structural similarity based search and kinome wide interaction profiling were employed with molecular docking validation. Gene ontology (GO) enrichment analysis and protein-protein interaction (PPI) network based illustrations were utilized to prioritize target-pathway and disease relationships. Data illustrated that BPA possessed multi-target nature since this chemical potentially interacted with various protein targets where many of these were validated through docking. Potential BPA targets were significantly enriched to various cellular signaling pathways including steroid biosynthesis, peroxisome proliferator-activated receptor gamma (PPARℽ) and cancer. Further, hypertension was prioritized as disease target. In addition, BPA targeted 17 cell signaling kinases encompassed in the human kinome. In addition, inflammatory (5-LO) and apoptosis regulators (Bcl-X and Bcl-2) were also explored as novel targets. Evidence indicates that the multi-target nature and plausible mechanisms underlying BPA actions in a system wide manner aids toward understanding of adverse effects. This observation may lead us to more precise method to elucidate the toxico-pathogenic mechanisms of BPA with an environmental health perspective.

The association between urinary bisphenol A levels and nonalcoholic fatty liver disease in Korean adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017

BackgroundNonalcoholic fatty liver disease (NAFLD) is becoming a global health problem. Bisphenol A (BPA), one of most widely used environmental chemicals, is suspected to be a contributor to the development NAFLD. This study was performed to examine the relationship between human BPA levels and risk of NAFLD.MethodsThe data (n = 3476 adults: 1474 men and 2002 women) used in this study were obtained from the Korean National Environmental Health Survey III (2015-2017). BPA levels were measured in urine samples. NAFLD was defined using hepatic steatosis index after exclusion of other causes of hepatic diseases.ResultsThere was a significant linear relationship between the elevated urinary BPA concentrations and risk of NAFLD. In a univariate analysis, odds ratio (OR) of the highest quartile of urinary BPA level was 1.47 [95% confidence interval (CI) 1.11-1.94] compared to the lowest quartile. After adjusted with covariates, the ORs for NAFLD in the third and fourth quartiles were 1.31 [95% CI 1.03-1.67] and 1.32 [95% CI 1.03–1.70], respectively.ConclusionsUrinary BPA levels are positively associated with the risk of NAFLD in adults. Further experimental studies are needed to understand the molecular mechanisms of BPA on NAFLD prevalence.

BPA-induced prostatic hyperplasia in vitro is correlated with the unbalanced gene expression of AR and ER in the epithelium and stroma

As a typical environmental endocrine disruptor (EED), bisphenol A (BPA) can induce pathological hyperplasia of the prostatic epithelium and stroma. This study concentrates mainly on the effect and underlying mechanisms of BPA on prostatic hyperplasia, which is based on the culture of primary human prostate epithelial cells (HPEpiC) and human prostate fibroblasts (HPrF). In an effect to screen the optimal pro-survival BPA levels, HPEpiC and HPrF were, respectively, exposed to concentration gradients of BPA (10-12M-10-4M) solution diluted with two corresponding medium and incubated for 72h at 37°C. CCK-8 assay showed that 10-9 M-10-5M BPA could facilitate the proliferation of HPEpiC, while similar proliferative effect of HPrF only needed 10-11 M-10-7M BPA. HPrF were more sensitive to BPA than HPEpiC. The qualification of PCNA gene expression measured using quantitative real-time polymerase chain reaction (qRT-PCR) also mirrored the BPA-induced cell proliferation. Additionally, our results considered that androgen receptor (AR), estrogen receptor (ERα, ERβ), and NFKB1 gene expressions exhibited up-regulation in HPEpiC treated with 10-9M BPA for 72h. However, in HPrF, the identical BPA treatment could activate ERα, ERβ, and NFKB1 gene expressions and down-regulated the expression of AR levels. It is further confirmed that low-dose BPA can indeed promote the proliferation of human prostate cells in vitro, and the mechanisms of BPA for prostatic epithelial and stromal hyperplasia may not be consistent.

Bisphenol A impairs cognitive function and 5-HT metabolism in adult male mice by modulating the microbiota-gut-brain axis

Bisphenol A (BPA) has been found to promote hepatotoxicity, reproductive toxicity, and developmental toxicity. However, the neurotoxicity and mechanism of BPA on cognitive function are still unclear. To that end, eight-week-old adult male and female C57BL/6J mice were exposed to 0.05, 0.5, 5, and 50 mg/kg BPA by dietary supplementation for 22 weeks. BPA exposure impaired learning and memory in male mice, associated with increased neuroinflammation and damaged blood-brain barrier. BPA exposure reduced the tight junctions in the colon, resulting in dysfunction of the gut barrier. The levels of neurotransmitters in the serum, hippocampus, and colon of male mice, including tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, were all decreased by BPA, together with reduced expression of tryptophan and 5-HT metabolism-related genes. Cecal microbiota analysis revealed that the diversity and composition of the microbiota in male mice were markedly altered by BPA, leading to functional profile changes in the microbial community. These results suggest that the neurotoxicity of BPA in male mice may be partly regulated by the interactions of the microbiota-gut-brain axis. However, BPA has little effect on the cognitive function in female mice, which might be caused by the microbial differences and the role of estrogen receptors.

Bisphenol A and Its Analogues Exhibit Different Cytotoxic and Mitochondrial Dysfunction Potential in Human Granulosa Cells

Bisphenol A (BPA) is an environmental endocrine disruptor and has been strongly associated with the development of numerous diseases, including ovarian follicle development disorders. BPA is being replaced by structurally similar chemicals, such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). However, the toxicity of these analogues in female reproduction is unclear. Here, we investigated the induction of cytotoxicity and mitochondrial dysfunction in the human granulosa cell line KGN by BPA and its selected analogues. We found that BPA and its analogues, especially BPAF, significantly reduced cell viability and caused cytotoxicity. Furthermore, we observed that BPA and BPAF significantly reduced mitochondrial function, including decreasing ATP generation, promoting ROS production and increasing intracellular Ca2+ levels. An oxidative-antioxidant imbalance was also detected after exposure to these chemicals. In contrast, the total antioxidant capacity was significantly reduced. To our knowledge, this is the first report on the evaluation of the potential of BPA and its analogues to induce cytotoxicity and mitochondrial dysfunction in ovarian granulosa cells. Our study revealed the possible mechanism of BPA and its analogues inducing granulosa cell damage and suggested that mitochondrial dysfunction may play an important regulatory role in bisphenol-induced follicular development disorders.

Comparative Study of Bisphenol A and Its Selected Analogues on the Induction of Mitochondrial Mass Loss and Apoptosis in Human Granulosa Cells

It has been confirmed that the occurrence of a variety of chronic diseases including female infertility is closely related to bisphenol A (BPA) exposure. BPA is now being gradually replaced by its analogues. Although the adverse health effects of BPA have been extensively studied, little is known about the female reproductive toxicity of its analogues, particularly BPS, BPF and BPAF. The present study evaluated the effects of BPA and its analogues BPS, BPF and BPAF on mitochondrial mass and potential to induce apoptosis in KGN cells. We observed that BPA and its analogues, especially BPA and BPAF exposure can significantly reduce mitochondrial mass. This reduction in mitochondrial mass was confirmed by flow cytometry after labelling the NAO probe. The significant induction effect of BPA and its analogues on KGN cell apoptosis was detected using flow cytometry. Compared with BPA and BPAF, the interference effect of BPS and BPF on KGN cells was smaller, although there were significant differences between the high-concentration treatment groups and the control group. Our study revealed the possible mechanisms of BPA and its analogues on granulosa cell damage and female sterility. In addition, it also suggests that the safety of BPA analogues in female reproduction needs to be reconsidered.

Bisphenol A and thyroid hormones: Bibliometric analysis of scientific publications.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical which can cause potential health risks and interfere with thyroid hormones through multiple avenues. This study aimed to evaluate the hotspots and emerging trends on BPA and thyroid hormones by using a bibliometric method.Publications related on BPA and thyroid hormones were downloaded from Science Citation Index-Expanded database. Annual outputs, high yield journals, countries, institutions, authors and their cited times were summarized. In addition, keywords co-occurrence, burst references and citation networks were bibliometric analyzed.From 2000 to 2019, 418 articles were published. Both of the Environment International and Environmental Health Perspectives, United States, Chinese Academy of Sciences and Antonia M. Calafat were the most recorded journals, countries, institutions and authors, respectively. The main research area was Toxicology. In addition of the retrieve term “bisphenol-a” and “thyroid-hormone”, “in-vitro”, “exposure” and “endocrine disruptors”, were the hotspot keywords and “triclosan”, “oxidative stress” and “united-states” were the most recent trends keywords. “Thyroid hormone action is disrupted by Bisphenol A as an antagonist” published on The Journal of Clinical Endocrinology & Metabolism by Kenji Moriyama in 2002 got both the highest burst score and citation score. Six groups were clustered and the mechanism of BPA's effect on thyroid hormones, and the exposure of BPA and potential risks in children and pregnant women were the two main large fields.The number of publications in the field of BPA and thyroid hormones has increased tremendously since 2000. The research hotspot ranged from mechanism researches in animal models to epidemiological studies. “Thyroid hormone action is disrupted by bisphenol A as an antagonist” of Kenji Moriyama provided important building blocks in the field. The impact of BPA on thyroid hormones, especially pregnant women and children, was the latest research frontiers and might be the future direction of this filed in the following years.

Regulating Age-Related Hearing Loss with Bisphenol A via the Long Non-Coding RNA X Inactive Specific Transcript and MicroRNA-34a-5p Pathways

Age-related hearing loss (AHL) is a common, high-incidence, perceptual disease in the elderly population worldwide. Since bisphenol A (BPA) has been reported to associate with cell apoptosis, we hypothesize that BPA can inhibit the neuronal apoptosis in AHL. Forty Wistar rats were recruited to model AHL; they were then treated with different doses of BPA. We used auditory brainstem response testing to measure the BPA-induced improvement in the rats’ hearing. We examined the proliferation and apoptosis of the auditory cortical neurons in the rats with MTT assay and flow cytometry. Also, to delineate the underlying mechanism of BPA’s effect on AHL, we quantitated the expression level of long non-coding RNA X inactive specific transcript (lncRNA XIST) and miR-34a-5p in the rats’ auditory cortex with a novel method called nanoparticle PCR. We found that BPA intervention improved the hearing of AHL model rats, enhanced neuronal cell proliferation, restricted neuronal cell apoptosis, upregulated miR-34a-5p levels, and downregulated lncRNA XIST levels. The dual-luciferase reporter (DLR) assay revealed that BPA inhibited the apoptosis of auditory cortex neurons by targeting miR-34a-5p with lncRNA XIST and regulated the process of AHL. Therefore, we come to a conclusion that BPA contributes to the improvement of AHL, which may be achieved by upregulating miR-34a-5p and inhibiting the apoptosis of auditory cortex neurons via lncRNA XIST.

Degradation and transformation of bisphenol A in UV/Sodium percarbonate: Dual role of carbonate radical anion

The bicarbonate and carbonate ions (HCO3− &CO32−) will consume hydroxyl radical (HO•) to generate carbonate radical anion (CO3•−) in hydroxyl radical based advanced oxidation processes (HO•−AOPs) resulting in reduced oxidation efficiencies of the systems. However, despite the HO• quenching effect of carbonate species, the contribution of CO3•− to the degradation of bisphenol A (BPA) was observed in UV/sodium percarbonate (UV/SPC). In order to study the performance of UV/SPC for BPA degradation and the role of CO3•− in this process, the degradation kinetics and mechanisms of BPA in UV/SPC and in UV/hydrogen peroxide (UV/H2O2) were compared at equivalent concentration of H2O2. In this study, the observed degradation rates of BPA by UV/SPC and by UV/H2O2 in Milli-Q water were similar. Variation of the BPA degradation rates in the presence of radical quenchers, tert-butanol and phenol, suggested that both CO3•− and HO• contributed to the degradation of BPA in UV/SPC. Second order rate constant of CO3•− towards BPA (kCO3•−+BPA = 2.23 × 108 M−1 s−1) and steady state concentrations of CO3•− ([CO3•−]ss = 2.3 × 10−12 M) and HO• ([HO•]ss = 1.82 × 10−14 M) in UV/SPC were determined with competition kinetics at 1 mM SPC and pH 8.5. The high [CO3•−]ss observed in UV/SPC compensated for the smaller kCO3•−+BPA compared to kHO•+BPA and the consumption of HO• making the degradation rate of BPA in UV/SPC comparable to that in UV/H2O2. Detailed studies on identification of transformation products (TPs) of BPA in UV/SPC revealed that phenol ring and isopropylidene bridge were the main reactive sites of BPA. Degradation pathways were proposed accordingly. The results of kinetic and mechanistic studies provide better fundamental understanding of the degradation of BPA in UV/SPC and HCO3−&CO32− impact on BPA degradation by HO•−AOPs. This also demonstrates potential for CO3•− based water purification technologies.

Vitis vinifera (grape) seed extract and resveratrol alleviate bisphenol-A-induced metabolic syndrome: Biochemical and molecular evidences.

The mechanisms of bisphenol-A (BPA)-induced metabolic syndrome as well as the protective role of grape seed extract (GSE) and resveratrol were investigated. Rats were treated with BPA (0 and 35mg·kg-1 ·day-1 , gavage) plus resveratrol (25, 50, and 100mg·kg-1 ·day-1 , i.p.) or GSE (3, 6, 12mg·kg-1 ·day-1 , i.p.) or vitamin E (200IU/kg/every other day, i.p.). After 2months, mean systolic blood pressure, serum lipid profile, glycaemia, and fat index were examined. By enzyme-linked immunosorbent assay, the serum concentrations of insulin, leptin, adiponectin, and paraoxonase 1, and by real-time polymerase chain reaction as well as western blotting, key liver elements in cholesterol hemostasis (LDLR, CYP7A1, ABCG5 and 8) and insulin signaling (p-Akt/Akt and p-PI3K/PI3K) were measured. BPA increased mean systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol and reduced paraoxonase1 and the hepatic expression of both ABCG5 and ABCG8. It increased the body fat index, leptin, adiponectin, insulin, and glycaemia level and decreased the hepatic protein expression of p-Akt/Akt and p-PI3K/PI3k. GSE, resveratrol, or vitamin E coadministration along with BPA restored the detrimental effects of BPA in some levels. Herein, the predisposing effects of BPA-induced metabolic syndrome were restored by GSE and resveratrol, linked to the regulation of insulin signaling, ABCG8 expression, and their antioxidant properties.