Hypothalamic vasopressin sex differentiation is observed by embryonic day 15 in mice and is disrupted by the xenoestrogen bisphenol A.

Arginine vasopressin (AVP) neurons of the hypothalamic paraventricular region (AVPPVN) mediate sex-biased social behaviors across most species, including mammals. In mice, neural sex differences are thought to be established during a critical window around birth ( embryonic (E) day 18 to postnatal (P) day 2) whereby circulating testosterone from the fetal testis is converted to estrogen in sex-dimorphic brain regions. Here, we found that AVPPVN neurons are sexually dimorphic by E15.5, prior to this critical window, and that gestational bisphenol A (BPA) exposure permanently masculinized female AVPPVN neuronal numbers, projections, and electrophysiological properties, causing them to display male-like phenotypes into adulthood. Moreover, we showed that nearly twice as many neurons that became AVP+ by P0 were born at E11 in males and BPA-exposed females compared to control females, suggesting that AVPPVN neuronal masculinization occurs between E11 and P0. We further narrowed this sensitive period to around the timing of neurogenesis by demonstrating that exogenous estrogen exposure from E14.5 to E15.5 masculinized female AVPPVN neuronal numbers, whereas a pan-estrogen receptor antagonist exposed from E13.5 to E15.5 blocked masculinization of males. Finally, we showed that restricting BPA exposure to E7.5-E15.5 caused adult females to display increased social dominance over control females, consistent with an acquisition of male-like behaviors. Our study reveals an E11.5 to E15.5 window of estrogen sensitivity impacting AVPPVN sex differentiation, which is impacted by prenatal BPA exposure.

Modulation of Sirtuin 3 by N-Acetylcysteine Preserves Mitochondrial Oxidative Phosphorylation and Restores Bisphenol A-Induced Kidney Damage in High-Fat-Diet-Fed Rats.

Bisphenol A (BPA) and high-fat diets (HFD) are known to adversely affect the kidneys. However, the combined effects of both cases on kidney health and the potential benefits of N-acetylcysteine (NAC) in mitigating these effects have not been investigated. To explore these aspects, male Wistar rats were fed with HFD and allocated to receive a vehicle or BPA. At week twelve, the BPA-exposed rats were subdivided to receive a vehicle or NAC along with BPA until week sixteen. Rats fed HFD and exposed to BPA showed renal dysfunction and structural abnormalities, oxidative stress, inflammation, and mitochondrial dysfunction, with alterations in key proteins related to mitochondrial oxidative phosphorylation (OXPHOS), bioenergetics, oxidative balance, dynamics, apoptosis, and inflammation. Treatment with NAC for 4 weeks significantly improved these conditions. The findings suggest that NAC is beneficial in protecting renal deterioration brought on by prolonged exposure to BPA in combination with HFD, and modulation of sirtuin 3 (SIRT3) signaling by NAC appears to play a key role in the preservation of homeostasis and integrity within the mitochondria by enhancing OXPHOS activity, maintaining redox balance, and reducing inflammation. This study provides valuable insights into potential therapeutic strategies for preserving kidney health in the face of environmental and dietary challenges.

Cyanidin improves spatial memory and cognition in bisphenol A-induced rat model of Alzheimer's-like neuropathology by restoring canonical Wnt signaling.

INTRODUCTION: Research has unveiled the neurotoxicity of Bisphenol A (BPA) linked to neuropathological traits of Alzheimer's disease (AD) through varied mechanisms. This study aims to investigate the neuroprotective properties of cyanidin, an anthocyanin, in an in vivo model of BPA-induced Alzheimer's-like neuropathology. METHODS: Three-week-old Sprague-Dawley rats were randomly assigned to four groups: vehicle control, negative control (BPA exposure), low-dose cyanidin treatment (BPA + cyanidin 5 mg/kg), and high-dose cyanidin treatment (BPA + cyanidin 10 mg/kg). Spatial memory was assessed through behavioral tests, including the Y-maze, novel object recognition, and Morris water maze. After behavioral tests, animals were euthanized, and brain regions were examined for acetylcholinesterase inhibition, p-tau, Wnt3, GSK3ß, and ß-catenin levels, antioxidant activities, and histopathological changes. RESULTS: BPA-exposed groups displayed memory impairments, while cyanidin-treated groups showed significant memory improvement (p < 0.0001). Cyanidin down regulated p-tau and glycogen synthase kinase-3ß (GSK3ß) and restored Wnt3 and ß-catenin levels (p < 0.0001). Moreover, cyanidin exhibited antioxidant properties, elevating catalase and superoxide dismutase levels. The intervention significantly reduced the concentrations of acetylcholinesterase in the cortex and hippocampus in comparison to the groups treated with BPA (p < 0.0001). Significant gender-based disparities were not observed. CONCLUSION: Cyanidin demonstrated potent neuroprotection against BPA-induced Alzheimer's-like neuropathology by enhancing antioxidant defenses, modulating tau phosphorylation by restoring the Wnt/ß-catenin pathway, and ameliorating spatial memory deficits. This study highlights the therapeutic potential of cyanidin in countering neurotoxicity linked to BPA exposure.

Food contamination from packaging material with special focus on the Bisphenol-A.

Additives, such as bisphenol A (BPA) that are added to packaging material to enhance functionality may migrate into food products creating a concern for food safety. BPA has been linked to various chronic diseases, such as: diabetes, obesity, prostate cancer, impaired thyroid function, and several other metabolic disorders. To safeguard consumers, BPA migration limits have been defined by regulatory bodies. However, it is important to address the underlying factors and mechanisms so that they can be optimized in order to minimize BPA migration. In this review, we determine the relative importance of the factors, i.e. temperature, contact time, pH, food composition, storage time and temperature, package type, cleaning, and aging, and packaging damage that promote BPA migration in foods. Packaging material seems to be the key source of BPA and the temperature (applied during food production, storage, can sterilization and cleaning processes) was the critical driver influencing BPA migration.

Bisphenol a downregulates GLUT4 expression by activating aryl hydrocarbon receptor to exacerbate polycystic ovary syndrome.

BACKGROUND: Bisphenol A (BPA) levels are high in women with polycystic ovary syndrome (PCOS). The mechanism by which BPA induces abnormal glucose metabolism in PCOS patients is largely unknown. METHODS: Serum and urine samples were collected from women with and without PCOS (control) at the reproductive medicine center with informed consent. Non-PCOS patients who received in vitro fertilization were recruited for collection of ovarian follicular fluid and granular cells. Wild-type C57BL/6 and AhR -/- mice were used to verify the effects of BPA on PCOS. Real-time PCR, western blotting, and ELISA were conducted to analyze the function of BPA. Chip-qPCR verified the role of AhR in GLUT4 transcription. Flow cytometry was performed to determine glucose uptake. RESULTS: A positive correlation was observed between BPA concentration and serum BPA levels in PCOS patients. BPA aggravated the changes in PCOS with abnormal glucose metabolism, impaired fertility, and increased body fat. Mechanistically, we showed that BPA activated AhR and led to decreased glucose transport via GLUT4 downregulation in ovarian granular cells. Therefore, the use of inhibitors or knockout of AhR could effectively rescue BPA-induced metabolic disorders in PCOS mice. CONCLUSIONS: Our results revealed that BPA suppressed GLUT4 expression and induced abnormal glucose metabolism by activating AhR, causing insulin resistance, and is thus a potential contributor to the development of PCOS. Therefore, AhR could be a potential new therapeutic target for PCOS. Video Abstract.

A prioritization strategy for functional alternatives to bisphenol A in food contact materials.

The use of bisphenol A (BPA), a substance of very high concern, is proposed to be banned in food contact materials (FCMs) in the European Union. To prevent regrettable substitution of BPA by alternatives with similar or unknown hazardous properties, it is of importance to gain the relevant toxicological information on potential BPA alternative substances and monitor them adequately. We created an inventory of over 300 substances mentioned as potential BPA alternatives in regulatory reports and scientific literature. This study presents a prioritization strategy to identify substances that may be used as an alternative to BPA in FCMs. We prioritized 20 potential BPA alternatives of which 10 are less familiar. We subsequently reviewed the available information on the 10 prioritized less familiar substances regarding hazard profiles and migration potential obtained from scientific literature and in silico screening tools to identify a possible risk of the substances. Major data gaps regarding the hazard profiles of the prioritized substances exist, although the scarce available data give some indications on the possible hazard for some of the substances (like bisphenol TMC, 4,4-dihydroxybenzophenone, and tetrachlorobisphenol A). In addition, very little is known about the actual use and exposure to these substances. More toxicological research and monitoring of these substances in FCMs are, therefore, required to avoid regrettable substitution of BPA in FCM.

Plastic compounds and liver diseases: Whether bisphenol A is the only culprit.

Plastics, while providing modern conveniences, have become an inescapable source of global concern due to their role in environmental pollution. Particularly, the focus on bisphenol A (BPA) reveals its biohazardous nature and association with liver issues, specifically steatosis. However, research indicates that BPA is just one facet of the problem, as other bisphenol analogues, microplastics, nanoplastics and additional plastic derivatives also pose potential risks. Notably, BPA is implicated in every stage of non-alcoholic fatty liver disease (NAFLD) onset and progression, surpassing hepatitis B virus as a primary cause of chronic liver disease worldwide. As plastic contamination tops the environmental contaminants list, urgent action is needed to assess causative factors and mitigate their impact. This review delves into the molecular disruptions linking plastic pollutant exposure to liver diseases, emphasizing the broader connection between plastics and the rising prevalence of NAFLD.

Unveiling the potential of estrogen: Exploring its role in neuropsychiatric disorders and exercise intervention.

Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) and Parkinson's disease (PD), and other neuropsychiatric disorders as well in their sex differences. In nervous system, estrogen is an important regulator of cell development, synaptic development, and brain connectivity. Therefore, this review aimed to investigate the potential of estrogen system in the exercise intervention of neuropsychiatric disorders to better understand the exercise in neuropsychiatric disorders and its sex specific. Exercise can exert a protective effect in neuropsychiatric disorders through regulating the expression of estrogen and estrogen receptors, which are involved in neuroprotection, neurodevelopment, and neuronal glucose homeostasis. These processes are mediated by the downstream factors of estrogen signaling, including N-myc downstream regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), etc. In addition, exercise can act on the estrogen response element (ERE) fragment in the genes of estrogenic downstream factors like ß-amyloid precursor protein cleavase 1 (BACE1). However, there are few studies on the relationship between exercise, the estrogen signaling pathway, and neuropsychiatric disorders. Hence, we review how the estrogen signaling mediates the mechanism of exercise intervention in neuropsychiatric disorders. We aim to provide a theoretical perspective for neuropsychiatric disorders affecting female health and provide theoretical support for the design of exercise prescriptions.

Exposure to bisphenol A and fiber-type microplastics induce oxidative stress and cell damage in disk abalone Haliotis discus hannai: Bioaccumulation and toxicity.

Along with environmental pollution caused by rapid economic development and industrialization, plastic waste is emerging as a global concern in relation to marine ecosystems and human health. Among the microplastics, fiber-type microfibers (MF) and bisphenol A (BPA), which are widely used as plasticizers, do not decompose well in the ocean, and tend to accumulate in organisms, generating an increased oxidative stress response. This study investigated the abalones' antioxidant and cell death responses following exposure to the environmental pollutants MF and BPA. Levels of malondialdehyde (MDA) and DNA damage increased over time, demonstrating the degree of lipid peroxidation and DNA damage in abalones exposed to individual and combined environmental conditions of MF and BPA. Compared to the single MF and BPA exposure groups, the combined exposure group showed a higher expression of antioxidant enzymes. A similar pattern was seen in the expression of the apoptosis enzyme caspase-3. Both MF and BPA caused oxidative stress and antioxidant enzymes were expressed to alleviate it, but it is believed that cell damage occurred because the stress level exceeded the allowed range.

A novel long non-coding RNA linc-93.2 participates in bisphenol induced oxidative stress and macrophage polarization in red common carp (Cyprinus carpio).

Previous studies show that bisphenol A (BPA) and its analogs induce oxidative stress and promote inflammatory response. However, the key molecules in regulating this process remain unclear. Here, we report significant inductive effects of BPA and bisphenol AF (BPAF) on a newly found long non-coding RNA linc-93.2 accompanied by oxidative stress and activation of pro-inflammatory pathways in treated fish and fish primary macrophages. Silencing linc-93.2 in fish primary macrophages in vitro or fish in vivo significantly promotes the expression of anti-oxidative stress-related genes and anti-inflammatory cytokines. This inhibition of pro-inflammatory cytokine expression, showing cell status disruption towards to M2 polarization. Followed by exposure to BPA or BPAF, silencing linc-93.2 in vitro or in vivo significantly attenuates the increased production of reactive oxygen species and malondialdehyde level aroused by bisphenol treatment, possibly owing to the enhancement of total antioxidant capacity observed in cells and tissue after linc-93.2 knockdown. RNA-sequencing further revealed regulation of nuclear factor-kappa b (NF-κB) in linc-93.2's downstream network, combining with our previous observation on the upstream regulation of linc-93.2 via NF-κB, which together suggest a critical role of linc-93.2 in promoting NF-κB positive feedback loop that may be an important molecular event initiating the immunotoxicity of bisphenols.

TAN (tannic acid) inhibits BPA-induced pyroptosis of L8824 (grass carp hepatocytes) by regulating PTEN/PI3K/AKT pathway.

Bisphenol A (BPA) and its analogues are still one of the most important substances that pollute aquatic systems and pose a threat to aquatic organisms. Tannic acid (TAN) is a kind of glycosyl compound, which has the functions of anti-oxidation, anti-inflammation and anti-apoptosis. However, it is unknown if BPA can regulate PTEN/PI3K/AKT pathway to induce pyroptosis of grass carp hepatocytes (L8824) and the antagonistic effect of tannic acid (TAN) through oxidative stress. Therefore, we established the grass carp hepatocytes (L8824) cell model treated with BPA. The oxidative stress indexes (SOD, CAT, GSH, H2O2 and T-AOC) were detected by oxidative stress kit, mRNA and protein expression of associated genes were examined using qRT-PCR and western blotting. The results showed that BPA treatment increased the content of hydrogen peroxide and decreased the activities of antioxidant enzymes and antioxidants (SOD, CAT, GSH, and T-AOC) in L8824 cells. We also found that PTEN/PI3K/AKT pathway was activated dramatically and the expression of pyroptosis-related genes (GSDMD, NLRP3, Caspase1, ASC and IL-1ß) was increased significantly. In addition, TAN could significantly reduce the toxicity of BPA on L8824 cells. After the addition of PTEN specific inhibitor SF1670, the activation of PTEN/PI3K/AKT pathway decreased by BPA was inhibited and the expression of scorch related genes was decreased. On the whole, TAN inhibits BPA-induced pyroptosis of L8824 by modulating the PTEN/PI3K/AKT pathway. The present study provides a novel perspective for toxicological mechanism of BPA, and new insights into the detoxification mechanism of TAN.

Distinct epigenetic modulation of differentially expressed genes in the adult mouse brain following prenatal exposure to low-dose bisphenol A.

Bisphenol A (BPA) is a common component in the manufacture of daily plastic consumer goods. Recent studies have suggested that prenatal exposure to BPA can increase the susceptibility of offspring to mental illness, although the underlying mechanisms remain unclear. In this study, we performed transcriptomic and epigenomic profiling in the adult mouse brain following prenatal exposure to low-dose BPA. We observed a sex-specific transcriptional dysregulation in the cortex, with more significant differentially expressed genes was observed in adult cortex from male offspring. Moreover, the upregulated genes primarily influenced neuronal functions, while the downregulated genes were significantly associated with energy metabolism pathways. More evidence supporting impaired mitochondrial function included a decreased ATP level and a reduced number of mitochondria in the cortical neuron of the BPA group. We further investigated the higher-order chromatin regulatory patterns of DEGs by incorporating published Hi-C data. Interestingly, we found that upregulated genes exhibited more distal interactions with multiple enhancers, while downregulated genes displayed relatively short-range interactions among adjacent genes. Our data further revealed decreased H3K9me3 signal on the distal enhancers of upregulated genes, whereas increased DNA methylation and H3K27me3 signals on the promoters of downregulated genes. In summary, our study provides compelling evidence for the potential health risks associated with prenatal exposure to BPA, and uncovers sex-specific transcriptional changes with a complex interplay of multiple epigenetic mechanisms.

Multiphase Ozonolysis of Bisphenol A: Chemical Transformations on Surfaces in the Environment.

High global plastic production volumes have led to the widespread presence of bisphenol compounds in human living and working environments. The most common bisphenol, bisphenol A (BPA), despite being endocrine disruptive and estrogenic, is still not fully banned worldwide, leading to continued human exposure via particles in air, dust, and surfaces in both outdoor and indoor environments. While its abundance is well documented, few studies have addressed the chemical transformations of BPA, the properties of its reactive products, and their toxicity. Here, the first gas-surface multiphase ozonolysis experiment of BPA thin films, at a constant ozone mixing ratio of 100 ppb, was performed in a flow tube for periods up to 24 h. Three transformation products involving the addition of 1, 2, and 3 oxygen atoms to the molecule were identified by LC-ESI-HRMS analyses. Exposure of indoor air to thin BPA surface films and BPA-containing thermal paper over periods of days validated the flow tube experiments, demonstrating the rapid nature of this multiphase ozonolysis reaction at atmospherically relevant ozone levels. Multiple transformation pathways are proposed that are likely applicable to not only BPA but also emerging commercial bisphenol products.

The Impact of Bisphenol A on the Anaerobic Sulfur Transformation: Promoting Sulfur Flow and Toxic H2S Production.

Bisphenol A (BPA), as a typical leachable additive from microplastics and one of the most productive bulk chemicals, is widely distributed in sediments, sewers, and wastewater treatment plants, where active sulfur cycling takes place. However, the effect of BPA on sulfur transformation, particularly toxic H2S production, has been previously overlooked. This work found that BPA at environmentally relevant levels (i.e., 50-200 mg/kg total suspended solids, TSS) promoted the release of soluble sulfur compounds and increased H2S gas production by 14.3-31.9%. The tryptophan-like proteins of microbe extracellular polymeric substances (EPSs) can spontaneously adsorb BPA, which is an enthalpy-driven reaction (ΔH = -513.5 kJ mol-1, ΔS = -1.60 kJ mol-1K -1, and ΔG = -19.52 kJ mol-1 at 35 °C). This binding changed the composition and structure of EPSs, which improved the direct electron transfer capacity of EPSs, thereby promoting the bioprocesses of organic sulfur hydrolysis and sulfate reduction. In addition, BPA presence enriched the functional microbes (e.g., Desulfovibrio and Desulfuromonas) responsible for organic sulfur mineralization and inorganic sulfate reduction and increased the abundance of related genes involved in ATP-binding cassette transporters and sulfur metabolism (e.g., Sat and AspB), which promoted anaerobic sulfur transformation. This work deepens our understanding of the interaction between BPA and sulfur transformation occurring in anaerobic environments.

Screening of the Antagonistic Activity of Potential Bisphenol A Alternatives toward the Androgen Receptor Using Machine Learning and Molecular Dynamics Simulation.

Over the past few decades, extensive research has indicated that exposure to bisphenol A (BPA) increases the health risks in humans. Toxicological studies have demonstrated that BPA can bind to the androgen receptor (AR), resulting in endocrine-disrupting effects. In recent investigations, many alternatives to BPA have been detected in various environmental media as major pollutants. However, related experimental evaluations of BPA alternatives have not been systematically implemented for the assessment of chemical safety and the effects of structural characteristics on the antagonistic activity of the AR. To promote the green development of BPA alternatives, high-throughput toxicological screening is fundamental for prioritizing chemical tests. Therefore, we proposed a hybrid deep learning architecture that combines molecular descriptors and molecular graphs to predict AR antagonistic activity. Compared to previous models, this hybrid architecture can extract substantial chemical information from various molecular representations to improve the model's generalization ability for BPA alternatives. Our predictions suggest that lignin-derivable bisguaiacols, as alternatives to BPA, are likely to be nonantagonist for AR compared to bisphenol analogues. Additionally, molecular dynamics (MD) simulations identified the dihydrotestosterone-bound pocket, rather than the surface, as the major binding site of bisphenol analogues. The conformational changes of key helix H12 from an agonistic to an antagonistic conformation can be evaluated qualitatively by accelerated MD simulations to explain the underlying mechanism. Overall, our computational study is helpful for toxicological screening of BPA alternatives and the design of environmentally friendly BPA alternatives.

Advances in optical and electrochemical sensing of bisphenol a (BPA) utilizing microfluidic Technology: A mini perspective.

Continuous exposure to toxic pollutants highlights the need for sensitive detection technologies that can be rapidly applied in the current world for quick screening of real samples. Bisphenol A (BPA) is one of the most common environmental contaminants, and it has the potential to harm both the environment and human health, notably causing reproductive disorders, cancer, heart disease, infertility, mental disorders, etc. Thus, significant attention has been paid to the detection of BPA and microplastics to promote food safety, environmental health, and human health on a sustainable earth. Among the current technologies, microfluidic based systems have garnered a lot of interest as future diagnostic tools for healthcare applications. Microfluidic devices can be deployed for quick screening and real-time monitoring, with inherent advantages like portability, miniaturisation, highly sensing tool and ease of integration with various detection systems. Optical and electrochemical sensors are two major analytical tools found in almost all microfluidic-based devices for ultrasensitive BPA and microplastics determination. In this review, we have evaluated and discussed microfluidic-based detection methods for BPA and microplastics.

Molecularly imprinted photopolymers combined with smartphone-based optical sensing for selective detection of bisphenol A in foods.

Bisphenol A (BPA), known for its endocrine-disrupting properties and potential to leach into food products, has led to significant food safety concerns. Therefore, the development of sensitive and selective BPA rapid detection methods is crucial. In this study, molecularly imprinted solid-phase extraction coupled to a colorimetric method was adopted for the smartphone-based determination of BPA. The molecularly imprinted polymer (MIP) was prepared via photopolymerization and used as a selective adsorbent material for SPE columns. The solid-phase extraction (SPE) columns with multiple cycles significantly reduced the extraction time to only 30 min. The developed method demonstrates useful sensitivity for BPA (LOD = 30 ppb). Furthermore, BPA migration from plastic packaging was evaluated under different storage conditions, revealing that microwave treatment for 5 min led to BPA release from polycarbonate packaging in juice and basic solutions. The MIP selective extraction/clean-up and smartphone-based optical sensor were successfully applied to BPA standard solutions and complex food samples (e.g., juice and tap water), resulting in reproducible and selective BPA determination (RSD ≤ 6%, n = 3). This rapid and cost-effective method of producing MIPs for BPA offers a promising solution for fast and low-cost sensing for on-site fresh food analysis.

Exposure to low dose of Bisphenol A (BPA) intensifies kidney oxidative stress, inflammatory factors expression and modulates Angiotensin II signaling under hypertensive milieu.

Humans are constantly exposed to low concentrations of ubiquitous environmental pollutant, Bisphenol A (BPA). Due to the prevalence of hypertension (one of the major risk factors of cardiovascular disease [CVD]) in the population, it is necessary to explore the adverse effect of BPA under hypertension associated pathogenic milieu. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME) induced hypertensive Wistar rats to low dose BPA (50 µg/kg) for 30 days period. In tissue samples immunohistochemistry, real-time quantitative polymerase chain reaction and enzymatic assays were conducted. Moreover, studies on primary kidney cell culture were employed to explore the impact of low dose of BPA exposure at nanomolar level (20-80 nM range) on renal cells through various fluorescence assays. The observed results illustrate that BPA exposure potentiates/aggravates hypertension induced tissue abnormalities (renal fibrosis), oxidative stress (ROS generation), elevated angiotensin-converting enzyme activity, malfunction of the antioxidant and tricarboxylic acid cycle enzymes, tissue lipid abnormalities and inflammatory factor expression (both messenger RNA and protein level of TNF-α and IL-6). Further, in vitro exposure of nM levels of BPA to primary kidney cells modulates oxidative stress (both superoxide and total ROS), mitochondrial physiology (reduced mitochondrial transmembrane potential-∆ψm) and lipid peroxidation in a dose dependent manner. In addition, angiotensin II induced ROS generation was aggravated further by BPA during coexposure in kidney cells. Therefore, during risk assessment, a precise investigation on BPA exposure in hypertensive (CVD vulnerable) populations is highly suggested.

Bisphenol A regulates bladder cells responses via control of G2/M-phase cell cycle, apoptotic signaling, MAPK pathway, and transcription factor-associated MMP modulation.

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, is widely used to produce polycarbonate plastics. The widely used BPA has been detected in human urine samples, raising public anxiety about the detrimental effects of BPA on the bladder. In this study, we explored regulatory mechanisms for the adverse effects of BPA in human bladder BdFC and T24 cells. BPA induced extrinsic and intrinsic apoptosis and G2/M cell cycle arrest caused by the ATM-CHK1/CHK2-CDC25c-CDC2 signaling, which ultimately inhibited the growth of human bladder cells. We also found that BPA decreased the binding activity of AP-1 and NF-κB transcription factors in human bladder cells, which inhibited migration and invasion through matrix metallopeptidase-2 and -9 inactivation. Phosphorylation of MAPKs was implicated with BPA-mediated detrimental effects in human bladder cells. Collectively, our results provide a novel explanation for the underlying molecular mechanisms that BPA induces cytotoxicity in human bladder cells.

18ß-Glycyrrhetinic acid exerts cardioprotective effects against BPA-induced cardiotoxicity through antiapoptotic and antioxidant mechanisms.

Bisphenol A (BPA) is a synthetic environmental pollutant widely used in industry, as well as is an endocrine disrupting chemicals and has a toxic effects on heart tissue. The aim of this study is to reveal the cardioprotective effects of 18ß-glycyrretinic acid (GA) against BPA-induced cardiotoxicity in rats. In this study, 40 male rats were used and five different groups (each group includes eight rats) were formed. The rats were applied BPA (250 mg/kg b.w.) alone or with GA (50 and 100 mg/kg b.w.) for 14 days. Rats were killed on Day 15 and heart tissues were taken for analysis. GA treatment decreased serum lactate dehydrogenase and creatine kinase MB levels, reducing BPA-induced heart damage. GA treatment showed ameliorative effects against lipid peroxidation and oxidative stress caused by BPA by increasing the antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase, and catalase) and GSH level of the heart tissue and decreasing the MDA level. In addition, GA showed antiapoptotic effect by increasing Bcl-2, procaspase-3, and -9 protein expression levels and decreasing Bax, cytochrome c, and P53 protein levels in heart tissue. As a result, it was found that GA has cardioprotective effects on heart tissue by exhibiting antioxidant and antiapoptotic effects against heart damage caused by BPA, an environmental pollutant. Thus, it was supported that GA could be a potential cardioprotective agent.