Biomimetic androgen receptor-based AIE biosensor for detecting bisphenol analogues: An integrating in silico topological analysis, molecular docking, and experimental validation study.

Bisphenol analogues are the typical class of endocrine disrupting chemicals (EDCs) that interfere with binding of endogenous hormones to androgen receptor (AR). With the expansion of industrial activities and the intensification of environmental pollution, an increasing array of bisphenol analogues is being released into the environment and food chain. This highlights the urgency to develop sensitive methods for the detection of bisphenol analogues. Here, we propose a biomimetic AR-based biosensor platform for detecting bisphenol analogues (BPF, TBBPA, and TBBPS) by binding with Aggregation-Induced Emission (AIE) probes. Following a comparison of the PROSS and ABACUS methods, biomimetic AR was designed using the ABACUS approach and subsequently expressed in vitro via the E. coli expression system. Through molecular docking and the observation of fluorescence changes upon binding with biomimetic AR, BS-46006 was selected as the AIE probe for the biosensor. The biomimetic AR-based biosensor showed sensitive detections of BPF, TBBPA, and TBBPS within a range of 0-50 mM. To further elucidate the multi-residue recognition mechanism, molecular orbitals, Electron Localization Function (ELF), and Localized Orbital Locator (LOL) were systematically calculated in this study. Lowest unoccupied molecular orbital and highest occupied molecular orbital indicated the energy gap of BPF, TBBPA, and TBBPS, which correspond to 0.12812, 0.19689, and 0.18711 eV, respectively. ELF and LOL offered clearer perspective through heat maps to visually represent the electron delocalization in BPF, TBBPA, and TBBPS. The matrix effect analysis suggested that the responses of bisphenol analogues in soil matrices could be effectively mitigated through sample pretreatment. The analysis of spiked soil samples showed the acceptable recoveries ranged from 91 % to 105 %. Additionally, the biomimetic AR-based AIE biosensor, which combines multi-residue detection with Tolerable Daily Intakes, shows great promise for the risk assessment of bisphenol analogues. This research may present a viable approach for the analysis of environmental pollutants.

Developmental exposures to common environmental pollutants result in long-term Reprogramming of hypothalamic-pituitary axis in mice.

Humans are exposed to a range of endocrine disrupting chemicals (EDCs). Many studies demonstrate that exposures to EDCs during critical windows of development can permanently affect endocrine health outcomes. Most experimental studies address changes in secretion of hormones produced by gonads, thyroid gland and adrenals, and little is known about the ability of EDCs to produce long-term changes in the hypothalamic-pituitary (HP) control axes. Here, we examined the long-term effects of three common EDCs on male mouse HP gene expression, following developmental exposures. Pregnant mice were exposed to 0.2 mg/ml solutions of bisphenol S (BPS), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), or 3,3',5,5'-tetrabromobisphenol A (TBBPA) from pregnancy day 8 through lactation day 21 (weaning day). Male offspring were left untreated until postnatal day 140, where pituitaries and hypothalami were collected. Pituitaries were assed for gene expression via RNA sequencing, while specific genes were assessed for expression in hypothalami via RT-qPCR. Differential expression, as well as gene enrichment and pathway analysis, indicated that all three chemicals induced long-term changes, (mostly suppression) in pituitary genes involved in its endocrine function. BPS and BDE-47 produced effects overlapping significantly at the level of effected genes and pathways. All three chemicals altered pathways of gonad and liver HP axes, while BPS altered HP-adrenal and BDE-47 altered HP-thyroid pathways specifically. All three chemicals reduced expression of immune genes in the pituitaries. Targeted gene expression in the hypothalamus indicates down regulation of hypothalamic endocrine control genes by BPS and BDE-47 groups, concordant with changes in the pituitary, suggesting that these chemicals suppress overall HP endocrine function. Interestingly, all three chemicals altered pituitary genes of GPCR-mediated intracellular signaling molecules, key signalers common to many pituitary responses to hormones. The results of this study show that developmental exposures to common EDCs have long-term impacts on hormonal feedback control at the hypothalamic-pituitary level.

Phototransformation of tetrabromobisphenol A bis (allyl ether) in an aqueous solution: Role of environmentally persistent free radicals.

Tetrabromobisphenol A bis (allyl ether) (TBBPA-BAE) represents an extensively used brominated flame retardant (BFRs) in the production of many fields and their phototransformation in natural water is still unclear. The environmentally persistent free radicals (EPFRs) with preserved activities could exist in the environment for a long time and involve in the phototransformation of many organic pollutants. Here, the photodegradation of TBBPA-BAE with the degradation rate constant (k = 0.060 h-1) under simulate sunlight and the promoting effect of EPFRs on TBBPA-BAE photodegradation (k = 0.135 h-1) were investigated. According to the detected photogenerated electrons (e-) and singlet oxygen (1O2) rather than hydroxyl radicals (•OH) by the electron paramagnetic resonance (EPR), the effect mechanism may not be related to the typical •OH induced by EPFRs. The possible transformation pathways of the ether cleavage, hydrolysis and hydroxylation of propenyl bond and the debromination were proposed by the primary byproducts identified by UPLC-Q-Exactive Orbitrap MS. EPFRs caused a further debromination and ether cleavage and probably be due to EPFRs directly providing electrons to TBBPA-BAE which promoted the photodegradation of TBBPA-BAE, and their reaction mechanism needed further attention. Overall, this study provided useful information to understand the role of EPFRs on phototransformation of TBBPA-BAE in water.

Green tea polyphenols alleviate TBBPA-induced gastric inflammation and apoptosis by modulating the ROS-PERK/IRE-1/ATF6 pathway in mouse models.

Green tea polyphenols (GTP), an important phytochemical in the daily human diet, bind to various cellular receptors and exert anti-inflammatory and antioxidant benefits. The environmental contaminant tetrabromobisphenol A (TBBPA) enters the digestive system through multiple pathways, resulting in oxidative stress (OS), gastroenteritis, and mucosal injury. The aim of this study was to explore the molecular mechanisms of TBBPA-induced gastritis in mice treated with GTP in vivo and in an in vitro model. The results showed that exposure to TBBPA increased reactive oxygen species (ROS) levels, activated oxidative stress (OS) induced endoplasmic reticulum stress (ERS), and the expression of endoplasmic reticulum stress-related factors (e.g., GRP78, PERK, IRE-1, ATF-6, etc.) increased. The inflammatory pathway NF-κB was activated, and the pro-inflammatory factors TNF-α, IL-1ß, and IL-6 increased, while triggering a cascade reaction mediated by caspase-3. However, the addition of GTP could inhibit OS, restore the balance of endoplasmic reticulum homeostasis, and improve the inflammatory infiltration and apoptosis of gastric mucosal epithelial cells. Therefore, GTP alleviated ERS, reduced inflammation and apoptosis, and restored the gastric mucosal barrier by alleviating TBBPA-induced OS in mouse gastric tissues and GES-1 cells. This provides basic information for exploring the antioxidant mechanism of GTP and further investigating the toxic effects of TBBPA on mouse gastric mucosa.

Combining transcriptomics and metabolomics to assess neurodevelopmental alteration caused by in utero exposure of mice to three putative thyroid hormone system disruptors.

Gestating mice were exposed to three chemicals, tetrabromo-bisphenol A (TBBPA; 2 mg/kg/day), amitrole (25 and 50 mg/kg/day) and pyraclostrobin (0.4 and 2 mg/kg/day) to assess their capacity to act as thyroid hormone disruptors and compromise neurodevelopment. Propyl-thio-uracyl, a known pharmacological inhibitor of thyroid gland secretion, was used at both high and low dose as a reference thyroid hormone system disruptor (1 ppm, 1500 ppm). A combination of plasma metabolomics and striatum transcriptomics revealed the induced change in pups at the postnatal stages. Although the underlying mechanism is unlikely to involve thyroid hormone disruption, these chemicals had a detectable effect on pups' neurodevelopment.

Low concentrations of tetrabromobisphenol A promote the biofilm formation of methicillin-resistant Staphylococcus aureus.

The effect and underlying mechanism of tetrabromobisphenol A (TBBPA), a plastic additive, on biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA USA300) remain unknown. This study first investigated the impact of different concentrations of TBBPA on the growth and biofilm formation of USA300. The results indicated that a low concentration (0.5 mg/L) of TBBPA promoted the growth and biofilm formation of USA300, whereas high concentrations (5 mg/L and 10 mg/L) of TBBPA had inhibitory effects. Further exploration revealed that the low concentration of TBBPA enhance biofilm formation by promoting the synthesis of extracellular proteins, release of extracellular DNA (eDNA), and production of staphyloxanthin. RTqPCR analysis demonstrated that the low concentration of TBBPA upregulated genes associated with extracellular protein synthesis (sarA, fnbA, fnbB, aur) and eDNA formation (atlA) and increased the expression of genes involved in staphyloxanthin biosynthesis (crtM), suggesting a potential mechanism for enhanced resistance of USA300 to adverse conditions. These findings shed light on how low concentrations of TBBPA facilitate biofilm formation in USA300 and highlight the indirect impact of plastic additives on pathogenic bacteria in terms of human health. In the future, in-depth studies about effects of plastic additives on pathogenicity of pathogenic bacteria should be conducted. CAPSULE: The protein and eDNA contents in biofilms of methicillin-resistant Staphylococcus aureus are increased by low concentrations of TBBPA.

Encapsulation and release of tetrabromobisphenol A in microplastics: Trade-off in their individual toxicity to Xenopus tropicalis tadpoles.

The toxicity of microplastics (MPs) to aquatic animals is closely related to the presence and release kinetics of contained additives, as most plastic products contain various additives. However, the relationship between the occurrence and release of additives from MPs, and their individual or combined toxicity remains unclear. In this study, the nanoscale distribution and release of tetrabromobisphenol A (TBBPA, a common flame retardant with endocrine-disrupting effect) in polystyrene (PS) MPs, and the long-term (60 days) toxicity of TBBPA and MPs containing TBBPA (at doses of 0 %, 1 %, 10 %, w/w) to Xenopus tropicalis tadpoles were investigated. Exposure to 10 µg/L TBBPA alone was the most toxics, while the encapsulation of TBBPA in MPs significantly delayed its lethal toxicity to tadpoles by inhibiting the rapid and extensive release of TBBPA. PS MPs alone and MPs containing 10 % TBBPA exhibited delayed survival toxicity compared to TBBPA alone, whereas PS MPs containing 1 % TBBPA did not show this effect but inhibited growth. These findings suggest that chronic toxicity assessments should be based on long-term (months or even years) exposure experiments due to the encapsulation-controlled slow release of toxic additives.

Olfactory toxicity of tetrabromobisphenol A to the goldfish Carassius auratus.

Tetrabromobisphenol A (TBBPA) is one of the most extensively used brominated flame retardants and its increasing use in consumer products has raised concerns about its ecotoxicity. Given the ubiquity of TBBPA in aquatic environments, it is inevitable that these chemicals will enter the olfactory chambers of fish via water currents. Nevertheless, the olfactory toxicity of TBBPA to aquatic organisms and the underlying toxic mechanisms have yet to be elucidated. Therefore, we investigated the olfactory toxicity of TBBPA in the goldfish Carassius auratus, a model organism widely used in sensory biology. Results showed that exposure to TBBPA resulted in abnormal olfactory-mediated behaviors and diminished electro-olfactogram (EOG) responses, indicating reduced olfactory acuity. To uncover the underlying mechanisms of action, we examined the structural integrity of the olfactory epithelium (OE), expression levels of olfactory G protein-coupled receptors (GPCRs), enzymatic activities of ion transporters, and fluctuations in neurotransmitters. Additionally, comparative transcriptomic analysis was employed to investigate the molecular mechanisms further. Our study demonstrates for the first time that TBBPA at environmentally relevant levels can adversely affect the olfactory sensitivity of aquatic organisms by interfering with the transmission of aqueous stimuli to olfactory receptors, impeding the binding of odorants to their receptors, disrupting the olfactory signal transduction pathway, and ultimately affecting the generation of action potentials.

[Research progress on the developmental toxicity and mechanism of brominated flame retardants during pregnancy exposure on offspring].

Brominated flame retardants (BFRs) are a kind of brominated compounds widely used in electronic and electrical appliances, textiles, construction materials and other industrial products to improve the flame retardant property. Because of its strong chemical stability, environmental persistence, long-distance transmission, biological accumulation, the exposure of humans and organisms in the ecosystem is increasing, and its potential biological effects are of great concern. Now BFRs can be detected in breast milk, serum, placenta and cord blood. Studies have shown that exposure to BFRs during pregnancy can lead to adverse birth outcomes such as low birth weight, malformation, gestational age changes and impairment of neurobehavioral development. This article summarizes the pollution and population exposure of three traditional BFRs, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), as well as the impact and mechanism of prenatal exposure on offspring birth outcomes and growth and development. It explores the harm of prenatal exposure to BFRs to offspring and proposes preventive measures for occupational populations for reference.

Association between brominated flame retardants (PBDEs and PBB153) exposure and hypertension in U.S. adults: results from NHANES 2005-2016.

BACKGROUND: Brominated Flame Retardants (BFRs) have attracted widespread concern due to their environmental persistence and potential toxicity. This study aims to examine the association between BFRs exposure and hypertension. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2016 for the cross-sectional analysis. To evaluate the individual and combined impacts of BFRs exposure on hypertension, we utilized multivariate models, including generalized additive models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. RESULTS: 9882 individuals (48% male) aged ≥ 20 were included in the final analysis, of whom 4114 had hypertension. After controlling for potential covariates, higher serum concentrations of PBDE100 (OR: 1.26; 95% CI: 1.01, 1.57) and PBDE153 (OR: 1.50; 95% CI: 1.18, 1.88) were significantly associated with hypertension. A nonlinear relationship between PBDE28 and hypertension was observed (P = 0.03). Moreover, BFRs mixture were positively associated with the prevalence of hypertension in both the WQS (ß:1.09; 95% CI: 1.02, 1.17; P = 0.02) and BKMR models. CONCLUSION: Our study suggested that BFRs exposure is positively associated with hypertension in the general population. To confirm this association and elucidate the mechanisms, further research is required.

Visible light-induced photocatalytic degradation of tetrabromobisphenol A on platinized tungsten oxide.

In this study, we investigated the degradation of the flame retardant tetrabromobisphenol A (TBBPA) using platinized tungsten oxide (Pt/WO3), synthesized via a simple photodeposition method, under visible light. The results of degradation experiments show a significant enhancement in TBBPA degradation upon surface platinization of WO3, with the degradation rate increasing by 13.4 times compared to bare WO3. The presence of Pt on the WO3 surface stores conduction band electrons, which facilitates the two-electron reduction of oxygen and enhances the production of valence band holes (hVB+) and hydroxyl radicals (●OH). Both hVB+ and ●OH are significantly involved in the degradation of TBBPA in the visible light-irradiated Pt/WO3 system. This was verified through fluorescence spectroscopy employing coumarin as a chemical probe and oxidizing species-quenching experiments. The analysis of degradation products and their toxicity assessment demonstrate that the toxicity of TBBPA-contaminated water is significantly reduced after Pt/WO3 photocatalysis. The degradation rate of TBBPA increased with increasing Pt/WO3 dosage, reached an optimum at a Pt content of 0.5 wt%, but decreased with increasing TBBPA concentration. The decrease in degradation efficiency of Pt/WO3 was minor, both in the presence of various anions and after repeated use. This study proposes that Pt/WO3 is a viable photocatalyst for the degradation of TBBPA in water under visible light.

Distribution, transformation, and toxic effects of the flame retardant tetrabromobisphenol S and its derivatives in the environment: A review.

As widely used alternative brominated flame retardants, tetrabromobisphenol S (TBBPS) and its derivatives have attracted increasing amounts of attention in the field of environmental science. Previous studies have shown that TBBPS and its derivatives easily accumulate in environmental media and may cause risks to environmental safety and human health. Therefore, to explore the environmental behaviours of TBBPS and its derivatives, in this paper, we summarized relevant research on the distribution of these compounds in water, the atmosphere, soil and food/biota, as well as their transformation mechanisms (biological and nonbiological) and toxic effects. The summary results show that TBBPS and its derivatives have been detected in water, the atmosphere, soil, and food/biota globally, making them a ubiquitous pollutant. These compounds may be subject to adsorption, photolysis or biological degradation after being released into the environment, which in turn increases their ecological risk. TBBPS and its derivatives can cause a series of toxic effects, such as neurotoxicity, hepatotoxicity, cytotoxicity, thyrotoxicity, genotoxicity and phytotoxicity, to cells or living organisms in in vitro and in vivo exposure. Toxicological studies suggest that TBBPS as an alternative to TBBPA is not entirely environmentally friendly. Finally, we propose future directions for research on TBBPS and its derivatives, including the application of new technologies in studies on the migration, transformation, toxicology and human exposure risk assessment of TBBPS and its derivatives in the environment. This review provides useful information for obtaining a better understanding of the behaviour and potential toxic effects of TBBPS and its derivatives in the environment.

Highly sensitive response to the toxicity of environmental chemicals in transparent casper zebrafish.

The response sensitivity to toxic substances is the most concerned performance of animal model in chemical risk assessment. Casper (mitfaw2/w2;mpv17a9/a9), a transparent zebrafish mutant, is a useful in vivo model for toxicological assessment. However, the ability of casper to respond to the toxicity of exogenous chemicals is unknown. In this study, zebrafish embryos were exposed to five environmental chemicals, chlorpyrifos, lindane, α-endosulfan, bisphenol A, tetrabromobisphenol A (TBBPA), and an antiepileptic drug valproic acid. The half-lethal concentration (LC50) values of these chemicals in casper embryos were 62-87 % of that in the wild-type. After TBBPA exposure, the occurrence of developmental defects in the posterior blood island of casper embryos was increased by 67-77 % in relative to the wild-type, and the half-maximal effective concentration (EC50) in casper was 73 % of that in the wild-type. Moreover, the casper genetic background significantly increased the hyperlocomotion caused by chlorpyrifos and lindane exposure compared with the wild-type. These results demonstrated that casper had greater susceptibility to toxicity than wild-type zebrafish in acute toxicity, developmental toxicity and neurobehavioral toxicity assessments. Our data will inform future toxicological studies in casper and accelerate the development of efficient approaches and strategies for toxicity assessment via the use of casper.

Insights into brominated flame retardant neurotoxicity: mechanisms of hippocampal neural cell death and brain region-specific transcriptomic shifts in mice.

Brominated flame retardants (BFRs) reduce flammability in a wide range of products including electronics, carpets, and paint, but leach into the environment to result in continuous, population-level exposure. Epidemiology studies have correlated BFR exposure with neurological problems, including alterations in learning and memory. This study investigated the molecular mechanisms mediating BFR-induced cell death in hippocampal cells and clarified the impact of hexabromocyclododecane (HBCD) exposure on gene transcription in the hippocampus, dorsal striatum, and frontal cortex of male mice. Exposure of hippocampus-derived HT-22 cells to various flame retardants, including tetrabromobisphenol-A (current use), HBCD (phasing out), or 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, phased out) resulted in time, concentration, and chemical-dependent cellular and nuclear morphology alterations, alterations in cell cycle and increases in annexin V staining. All 3 BFRs increased p53 and p21 expression; however, inhibition of p53 nuclear translocation using pifthrin-α did not decrease cell death. Transcriptomic analysis upon low (10 nM) and cytotoxic (10 µM) BFR exposure indicated that HBCD and BDE-47 altered genes mediating autophagy-related pathways. Further evaluation showed that BFR exposure increased LC3-II conversion and autophagosome/autolysosome formation, and co-exposure with the autophagy inhibitor 3-methyladenine (3-MA) attenuated cytotoxicity. Transcriptomic assessment of select brain regions from subchronically HBCD-exposed male mice demonstrated alteration of genes mediating vesicular transport, with greater impact on the frontal cortex and dorsal striatum compared with the dorsal and ventral hippocampus. Immunoblot analysis demonstrated no increases in cell death or autophagy markers, but did demonstrate increases in the SNARE binding complex protein SNAP29, specifically in the dorsal hippocampus. These data demonstrate that BFRs can induce chemical-dependent autophagy in neural cells in vitro and provide evidence that BFRs induce region-specific transcriptomic and protein expression in the brain suggestive of changes in vesicular trafficking.

Brominated flame retardants in surface sediment from Western Guangdong, South China: Occurrence, distribution and toxicity in Caenorhabditis elegans.

Sediment is the ultimate sink of environmental pollutants. A total of 128 surface sediment samples were collected from 8 rivers and 3 reservoirs in Maoming City, Guangdong Province. This study assessed the content and distribution of brominated flame retardants in sediments. The acute toxicity effects of tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDs) in sediments were evaluated using Caenorhabditis elegans as model organisms. The concentration of TBBPA in sediments ranged from not detected (ND) to 12.59 µg/kg and was mainly distributed in the central area, which was affected by the emission of TBBPA from residential and factory. The concentration of HBCDs ranged from ND to 6.31 µg/kg, and the diastereoisomer distribution was consistent, showing a trend close to the South China Sea. The composition pattern of HBCDs in the surface sediments from rivers were 41.73%-62.33%, 7.89%-25.54%, and 18.76%-40.65% for α-, ß-, and γ-HBCD, respectively, and in the sediments from reservoirs were 26.15%-45.52%, 7.44%-19.23%, and 47.04%-61.89% for α-, ß-, and γ-HBCD, respectively. When the sum of concentrations of TBBPA and HBCD in sediments were above high levels, reactive oxygen species in nematodes significantly increased, resulting in an oxidative stress response. Intestinal permeability was also enhanced, causing intestinal damage. In addition, in terms of this study, TBBPA had a greater impact on biotoxicity compared to HBCDs, and more attention should be paid to the toxic effects of the river ecosystem organisms in Maoming City, Guangdong Province. This study can complement the pollution database in the study area and provide basic data for pollution control.

Anaerobic treatment removing tetrabromobisphenol A and biota safety: How do tropical aquatic species respond to effluent toxicity over short- and long-term exposures?

Wastewater containing tetrabromobisphenol A (TBBPA), a commonly used flame retardant found in wastewater, can present significant toxic effects on biota, yet its impact on tropical freshwater environments is not well understood. This study explores the effectiveness of two independent anaerobic treatment systems, the acidogenic reactor (AR) and the methanogenic reactor (MR), for the ecotoxicity reduction of TBBPA-rich wastewater in four tropical freshwater species. Despite presenting good physicochemical performance and reduced toxicity of the influent for most species, AR and MR treatments remain acute and chronic toxicity. Overall, MR exhibited greater efficacy in reducing influent toxicity compared with AR. TBBPA bioaccumulation was observed in Chironomus sancticaroli after short-term exposure to 100% MR effluent. Multigenerational exposures highlighted changes in the wing length of C. sancticaroli, showing decreases after influent and AR exposures and increases after MR exposures. These findings underscore the need for ecotoxicological tools in studies of new treatment technologies, combining the removal of emerging contaminants with safeguarding aquatic biota. PRACTITIONER POINTS: Acidogenic and methanogenic reactors reduced the acute and chronic toxicity of wastewater containing tetrabromobisphenol A. Both treatments still exhibit toxicity, inducing short- and long-term toxic effects on four native tropical species. The aquatic species Pristina longiseta was most sensitive to effluents from acidogenic and methanogenic reactors. TBBPA concentrations recovered from Chironomus sancticaroli bioaccumulation analysis ranged from 1.07 to 1.35 µg g-1. Evaluating new treatment technologies with multiple species bioassays is essential for a comprehensive effluent toxicity assessment and ensuring aquatic safety.

Assessment of the disruption effects of tetrabromobisphenol A and its analogues on lipid metabolism using multiple in vitro models.

Tetrabromobisphenol A (TBBPA), a widely-used brominated flame retardant, has been revealed to exert endocrine disrupting effects and induce adipogenesis. Given the high structural similarities of TBBPA analogues and their increasing exposure risks, their effects on lipid metabolism are necessary to be explored. Herein, 9 representative TBBPA analogues were screened for their interference on 3T3-L1 preadipocyte adipogenesis, differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) to brown adipocytes, and lipid accumulation of HepG2 cells. TBBPA bis(2-hydroxyethyl ether) (TBBPA-BHEE), TBBPA mono(2-hydroxyethyl ether) (TBBPA-MHEE), TBBPA bis(glycidyl ether) (TBBPA-BGE), and TBBPA mono(glycidyl ether) (TBBPA-MGE) were found to induce adipogenesis in 3T3-L1 preadipocytes to different extends, as evidenced by the upregulated intracellular lipid generation and expressions of adipogenesis-related biomarkers. TBBPA-BHEE exhibited a stronger obesogenic effect than did TBBPA. In contrast, the test chemicals had a weak impact on the differentiation process of C3H10T1/2 MSCs to brown adipocytes. As for hepatic lipid formation test, only TBBPA mono(allyl ether) (TBBPA-MAE) was found to significantly promote triglyceride (TG) accumulation in HepG2 cells, and the effective exposure concentration of the chemical under oleic acid (OA) co-exposure was lower than that without OA co-exposure. Collectively, TBBPA analogues may perturb lipid metabolism in multiple tissues, which varies with the test tissues. The findings highlight the potential health risks of this kind of emerging chemicals in inducing obesity, non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism disorders, especially under the conditions in conjunction with high-fat diets.

Tetrabromobisphenol S (TBBPS) exposure causes gastric cell senescence and inflammation by inducing iron overload.

Tetrabromobisphenol S (TBBPS) is a brominated flame retardants (BFRs). TBBPS is widely used as a new type of BFR to replace TBBPA. Here, we used gastric cells as a model for evaluating the effect of TBBPS on the toxicology of gastric cells. Biochemical assays such as indirect immunofluorescence, cell proliferation assay were performed to analyze the toxicological effects of TBBPS on gastric cells. Cell proliferation analysis showed that TBBPS caused inhibition of gastric cell proliferation, and TBBPS induced gastric cell death. Further analysis showed that TBBPS led to ferroptosis and senescence of gastric cells by detecting ferroptosis-related marker molecules. Further work showed that TBBPS treatment resulted in lowered ferritin expression alongside heightened transferrin levels, which may be a potential molecular mechanism for TBBPS-induced ferroptosis and senescence in gastric cells. Here, our team investigates the effects of TBBPS on gastric cells in an in vitro model, and found that TBBPS caused toxicological damage to gastric cells. This study indicates potential toxic effects of TBBPS on the gastric cells, thereby providing a basis for further research into the toxicology of TBBPS.

Sub-inhibitory concentrations of tetrabromobisphenol A induce the biofilm formation of methicillin-resistant Staphylococcus aureus.

Biofilm formation by methicillin-resistant Staphylococcus aureus (MRSA) on indwelling medical devices complicates the treatment of infection. Tetrabromobisphenol A (TBBPA), a synthetic, lipophilic, halogenated aromatic compound widely used as an additive in plastics and electronic products, has raised environmental concerns due to its potential for bioaccumulation. This study investigated the impact of sub-inhibitory concentrations of TBBPA on MRSA biofilm formation. Crystal violet staining and confocal laser scanning microscopy analysis demonstrated that 1/8 MIC (0.5 µg/mL) of TBBPA significantly stimulated MRSA biofilm formation (P < 0.0001). MTT assays indicated that the metabolic activity within the biofilms increased by 15.60-40.85% compared to untreated controls. Dot blot immunoassay, autolysis assay, and extracellular DNA (eDNA) quantification further revealed TBBPA enhanced the production of polysaccharide intercellular adhesin (PIA) and eDNA, which are key biofilm components. Additionally, TBBPA was found to enhance the production of staphyloxanthin, facilitating MRSA survival under oxidative conditions and in human whole blood. RT-qPCR analysis showed that TBBPA significantly upregulated genes associated with biofilm formation (icaA, atlA, sarA), staphyloxanthin biosynthesis (crtM and sigB), and oxidative stress responses (sodA and katA). These findings suggest that TBBPA promotes MRSA biofilm development and enhances bacterial resistance to adverse conditions, thereby potentially exacerbating risks to human health.

Neurotoxicity of tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) through the GABAergic and serotonergic neurotransmission in Caenorhabditis elegans.

Tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a novel additive brominated flame retardant, is being developed for use in polyolefin and copolymers. Despite its emerging application, the neurotoxicity and mechanisms of action of TBBPA-BDBPE remain unexplored. Caenorhabditis elegans was utilized as the model organism to study the neurotoxic effects of TBBPA-BDBPE across environmental concentrations ranging from 0 to 100 µg/L. This investigation focused on various toxicological endpoints such as locomotive behavior, neuronal injury, neurotransmitter transmission, and the regulation of nervous system-related gene expression. Acute exposure to TBBPA-BDBPE at concentrations of 10-100 µg/L significantly impaired nematode movement, indicating potential neurotoxicity. In transgenic nematodes, this exposure also caused damage to γ-aminobutyric acid (GABAergic) and serotonergic neurons, along with notable changes in the levels of GABAergic and serotonergic neurotransmitters. Further molecular studies indicated alterations in neurotransmission-related genes (cat-4, mod-1, unc-25, and unc-47). Molecular docking analysis confirmed the binding affinity of TBBPA-BDBPE to key neurotransmission proteins-CAT-4, MOD-1, UNC-25, and UNC-47. These findings demonstrate that TBBPA-BDBPE exerts neurotoxic effects by impacting GABAergic and serotonergic neurotransmission in nematodes. This study provides new insights into the potential environmental risks of TBBPA-BDBPE.