Tetrabromobisphenol A Exposure Research Articles

Tetrabromobisphenol A reduces male rats reproductive organ coefficients and disrupting sexual hormone by causing oxidative stress

Tetrabromobisphenol A (TBBPA) has become a topic of public attention due to its pervasive detection in the environment and organisms in recent decades. However, limited information is available regarding the toxicity of TBBPA on reproductive ability of male mammals. Herein, the reproductive toxicity of TBBPA was investigated in male rats to fill the knowledge gap. In this study, male rats were exposed to TBBPA (0, 10, 100, and 1000 mg/kg) for 6 weeks. Subsequently, body and organ indexes, histopathological evaluation of testis and epididymis, ultrastructural observation of sperm, testosterone and progesterone levels, and oxidative stress indicators were conducted to reveal corresponding mechanisms. Results obtained showed that compare to the control group, the body weight, testes weight, epididymis weight, seminal vesicle and coagulation glands weight of rats in the 1000 mg/kg group lost 8.30%, 16.84%, 20.16%, 19.72% and 26.42%, respectively. Intriguingly, exposure to TBBPA (10, 100, 100 mg/kg) resulted in substantial pathological damage in testis, epididymis and sperm. TBBPA exposure also increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, as well as superoxide dismutase (T-SOD) and catalase (CAT) activities in testicular tissue. What’s more, the testosterone and progesterone levels in male rat serum were significantly decreased after exposure to TBBPA for 6 weeks. Meanwhile, results of molecular docking showed that TBBPA has a strong affinity with estrogen receptors (ERs). These findings demonstrated that TBBPA exposure negatively impacts the reproductive ability of male rats, thus providing new insights for risk assessment for reproductive health under TBBPA exposure.

Environmentally Relevant Concentrations of Tetrabromobisphenol A Exposure Impends Neurovascular Formation through Perturbing Mitochondrial Metabolism in Zebrafish Embryos and Human Primary Endothelial Cells.

Tetrabromobisphenol A (TBBPA), the most extensively utilized brominated flame retardant, has raised growing concerns regarding its environmental and health risks. Neurovascular formation is essential for metabolically supporting neuronal networks. However, previous studies primarily concerned the neuronal injuries of TBBPA, its impact on the neurovascularture, and molecular mechanism, which are yet to be elucidated. In this study, 5, 30, 100, 300 μg/L of TBBPA were administered to Tg (fli1a: eGFP) zebrafish larvae at 2-72 h postfertilization (hpf). The findings revealed that TBBPA impaired cerebral and ocular angiogenesis in zebrafish. Metabolomics analysis showed that TBBPA-treated neuroendothelial cells exhibited disruption of the TCA cycle and the Warburg effect pathway. TBBPA induced a significant reduction in glycolysis and mitochondrial ATP production rates, accompanied by mitochondrial fragmentation and an increase in mitochondrial reactive oxygen species (mitoROS) production in neuroendothelial cells. The supplementation of alpha-ketoglutaric acid, a key metabolite of the TCA cycle, mitigated TBBPA-induced mitochondrial damage, reduced mitoROS production, and restored angiogenesis in zebrafish larvae. Our results suggested that TBBPA exposure impeded neurovascular injury via mitochondrial metabolic perturbation mediated by mitoROS signaling, providing novel insight into the neurovascular toxicity and mode of action of TBBPA.

Green tea polyphenols inhibit TBBPA-induced lung injury via enhancing antioxidant capacity and modulating the NF-κB pathway in mice.

Tetrabromobisphenol A (TBBPA) is a global pollutant. When TBBPA is absorbed by the body through various routes, it can have a wide range of harmful effects on the body. Green tea polyphenols (GTPs) can act as antioxidants, resisting the toxic effects of TBBPA on animals. The effects and mechanisms of GTP and TBBPA on oxidative stress, inflammation and apoptosis in the mouse lung are unknown. Therefore, we established in vivo and in vitro models of TBBPA exposure and GTP antagonism using C57 mice and A549 cells and examined the expression of factors related to oxidative stress, autophagy, inflammation and apoptosis. The results of the study showed that the increase in reactive oxygen species (ROS) levels after TBBPA exposure decreased the expression of autophagy-related factors Beclin1, LC3-II, ATG3, ATG5, ATG7 and ATG12 and increased the expression of p62; oxidative stress inhibits autophagy levels. The increased expression of the pro-inflammatory factors IL-1β, IL-6 and TNF-α decreased the expression of the anti-inflammatory factor IL-10 and activation of the NF-κB p65/TNF-α pathway. The increased expression of Bax, caspase-3, caspase-7 and caspase-9 and the decreased expression of Bcl-2 activate apoptosis-related pathways. The addition of GTP attenuated oxidative stress levels, restored autophagy inhibition and reduced the inflammation and apoptosis levels. Our results suggest that GTP can attenuate the toxic effects of TBBPA by modulating ROS, reducing oxidative stress levels, increasing autophagy and attenuating inflammation and apoptosis in mouse lung and A549 cells. These results provide fundamental information for exploring the antioxidant mechanism of GTP and further for studying the toxic effects of TBBPA.

Photoaging enhances combined toxicity of microplastics and tetrabromobisphenol A by inducing intestinal damage and oxidative stress in Caenorhabditis elegans

Microplastics (MPs) are emerging environmental contaminants that often co-exist with tetrabromobisphenol A (TBBPA) in the environment. However, the joint effect of TBBPA and photoaged MPs at ambient concentrations remains unknown largely. In this study, the combined toxicity of ultraviolet-aged polystyrene (UV-PS) and TBBPA was investigated in Caenorhabditis elegans. UV irradiation could change the physical and chemical characteristics of polystyrene (PS), and UV-PS (90.218 μg/g) showed a stronger adsorption capacity than PS of 79.424 μg/g. Toxicity testing showed that 1 μg/L UV-PS enhanced the toxic effect of 1 μg/L TBBPA by reducing body length, locomotion behavior, and brood size in nematodes. Using ROS production, lipofuscin accumulation, and expression of gst-4::GFP as endpoints, the combined exposure of UV-PS and TBBPA induced stronger oxidative stress than TBBPA alone. Joint exposure to UV-PS and TBBPA significantly increased of Nile red and blue food dye in its intestinal tract compared to that in the TBBPA exposure group, indicating that co-exposure enhanced intestinal permeability. After co-exposure to UV-PS and TBBPA, the expression of the associated genes detected increased significantly. Therefore, UV-PS enhances the adverse effects of TBBPA through intestinal damage and oxidative stress in nematodes. These findings suggest that the co-presence of photoaged PS and TBBPA results in high environmental risks.

Tetrabromobisphenol A induces neuronal cytotoxicity by inhibiting PINK1-Parkin-mediated mitophagy via upregulating ATF3 expression

Tetrabromobisphenol A (TBBPA), as a widely used brominated flame retardant, has been implicated as a potential neurotoxicant. However, the mechanism of TBBPA-induced neurotoxicity has not been fully elucidated yet. In this study, using mouse hippocampal neuron cell HT22 as the in vitro model, the neuronal cytotoxicity of TBBPA and the mechanism by focusing on mitophagy have been studied. We found that neuronal cytotoxic effects were indeed induced by TBBPA exposure at concentrations of >20 μM for 24 h, including decreased cell viability (to 92.38 % at 20 μM; 18.25 % at 80 μM), enhanced ROS (enhanced 53.26 % at IC50 of 60 μM, compared with that in the control group) and mitochondrial ROS (mtROS) levels (enhanced 24.12 % at 60 μM), reduced mitochondrial membrane potential (MMP) (decreased 33.60 % at 60 μM). As a protective mechanism in cells, autophagy was initiated; however, mitophagy was inhibited, where PINK1 (PINK1-Parkin activation is critical in the depolarized MMP-induced mitophagy) expression was found to be repressed and decreased, further leading to the failure of Parkin recruitment to the damaged mitochondria. Mitophagy activator, nicotinamide mononucleotide (β-NMN) that activates the PINK1-Parkin pathway, could alleviate TBBPA-induced mitophagy deficiency and further reduce the neuronal cytotoxicity, demonstrating that TBBPA-induced PINK1-Parkin-mediated mitophagy deficiency contributed to the neuronal cytotoxicity. Furthermore, we found TBBPA caused the upregulation of Atf3 (activating transcription factor 3) gene transcription and expression levels, alongside reduced Pink1 levels; whereas enhanced Pink1 transcript levels were observed after ATF3 depletion even under TBBPA treatment, demonstrating TBBPA-induced overexpression of ATF3 should be responsible for the reduced PINK1 expression. Therefore, for the first time, here we demonstrate that TBBPA can inhibit PINK1-Parkin-mediated mitophagy via upregulating ATF3 expression, which further contributes to its neuronal cytotoxicity. This study should be able to improve our understanding of the mechanism of TBBPA-induced neuronal cytotoxicity.

Co-occurrence of tetrabromobisphenol a and debromination products in human hair across China: Implications for exposure sources and health effects on metabolic syndrome

The large usage of Tetrabromobisphenol A (TBBPA) in consumer products leads to ubiquitous distribution globally, however, studies on the occurrence of their debromination compounds were rather scarce. Also, though many studies illustrate the effectiveness of hair analysis to assess human exposure to organic pollutants, evidence on the associations with health implications is still fairly limited. Herein, 598 participants from across China were employed to investigate chronic, low-level exposure to TBBPA and debromination products by hair analysis. The geomean concentrations of TBBPA, 2,2′,6-tribromobisphenol A (Tri-BBPA), 2,2′- and 2,6-dibromobisphenol A (Di-BBPA), and 2-monobromobisphenol A (Mo-BBPA) were 1.07, 0.145, 0.135, and 0.894 ng/g, respectively, indicating nonnegligible health risks of debromination products. Hair analyte levels correlated with population age and population density among sampling regions. Sexual- and spatial-variations were observed with higher concentrations in females and in E-waste recycling sites. Logistic regression models showed that TBBPA exposure (adjusted odds ratio (OR): 1.02, 95 % confidential interval (CI): 1.01–1.05) was positively associated with risk of metabolic syndrome by adjusting for various covariates. These findings imply usefulness of hair as an alternative biomonitoring tool to assess human exposure to TBBPA and relative health effects, which highlights public concerns on co-exposure to these chemicals.

Long-Term Tetrabromobisphenol A Exposure Induces Gut Microbiota Imbalance and Metabolic Disorders via the Peroxisome Proliferator-Activated Receptor Signaling Pathway in the Regenerated Gut of Apostichopus japonicus.

Tetrabromobisphenol A (TBBPA), a commonly utilized brominated flame retardant, is found in many types of abiotic and biotic matrices. TBBPA can increase oxidative stress, disrupt the endocrine system, cause neurodevelopmental disorders and activate peroxisome proliferator-activated receptors to modulate lipid deposits in aquatic animals. However, the toxic mechanism of TBBPA on the gut microbiota and intestinal health remains unclear. Apostichopus japonicus is an ideal model for studying the relationship between environmental contaminants and intestinal health due to its unique capacity for evisceration and quickly regenerated intestine. In the present study, we investigated the toxic mechanism of TBBPA on the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. The results show that TBBPA exposure decreased the health of the regenerated intestine and the enzymatic activities, alpha diversity indices, and the relative abundance of the gut microbiota. Transcriptome analysis shows that TBBPA exposure affected lipid metabolism via the PPAR signaling pathway during the process of intestinal regeneration in A. japonicus, suggesting that TBBPA exposure can affect the composition and function of the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. These results provide a basis for further research on the potential toxicity of TBBPA to the intestinal health in animals.

TBBPA and lead co-exposure induces grass carp liver cells apoptosis via ROS/JAK2/STAT3 signaling axis

Tetrabromobisphenol A (TBBPA) and lead (Pb) are widely used in industrial field, which poses a serious threat to human and animal health. In particular, a large volume of wastewater containing TBBPA and Pb was discharged into the aquatic environment, causing a seriously negative impact on fish. Currently, whether TBBPA and Pb have a synergistic toxicity on fish remains unclear. In this study, we used the grass carp hepatocytes (L8824 cell line) exposed to either TBBPA or Pb, or both to determine their potential impacts on fish. The results showed that Pb or TBBPA induced oxidative stress and the loss of mitochondrial membrane potential in grass carp hepatocytes. In contrast to the control cells, the levels of JAK2, p-JAK2, STAT3 and p-STAT3 were significantly upregulated after exposure to TBBPA and Pb. Furthermore, the levels of Caspase3, Caspase9 and Bax were all increased while the level of Bcl2 was decreased in hepatocytes exposed to TBBPA or Pb. Results of flow cytometry and AO/EB staining reveled significant increases in the number of apoptotic cells in the TBBPA and Pb group compared to the controls. Notably, cells exposed to both TBBPA and Pb exhibited more severe damage than the single exposure, manifested by a higher number of apoptotic cells in the co-exposure group than the single exposure groups. Nevertheless, N-acetyl-l-cysteine (NAC) treatment could remarkably alleviate oxidative damage and loss of membrane potential in grass carp hepatocytes induced by TBBPA and Pb. Altogether, our study showed that combined exposure of TBBPA and Pb has a synergistic toxicity due to, inducing oxidative stress to activate JAK2/STAT3 signaling pathway, resulting in apoptosis of carp hepatocytes. This study shed a new light on the toxicological mechanism of exposure of TBBPA and Pb and provided a potential treatment of toxicity induced by TBBPA and Pb.

Toxicological evaluation of TBBPA by common carp (Cyprinus carpio) about the in vivo/vitro disturbance of the AHR pathway

Tetrabromobisphenol A (TBBPA) is a widely used plastic additive with high bioaccumulation potential and toxicity on both humans and wildlife. Currently, research on its ecotoxicity and the underlying mechanism is limited. Using common carp (Cyprinus carpio), we evaluated the toxicity of TBBPA, especially focusing on its alteration of a key metabolism-related pathway aryl hydrocarbon receptor (AHR), using in vivo/vitro assays and in silico simulation. The 96 h LC50 of TBBPA of common carp was 4.2 mg/L and belonged to the acute toxic level II. The bioaccumulation potential of TBBPA follows the role of liver > gill > brain and varies between 3- and 14-day exposure. On the AHR pathway respect, as expected, the metabolism-related cyp1a1 and cyp1b1 were upregulated in the liver and brain. Ahr2, the receptor, was also upregulated in the brain under TBBPA exposure. The alteration of gene expression was tissue-specific while the difference between 3- or 14-day exposure was minor. AHR inhibition assay indicated the 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AHR transactivation can be inhibited by TBBPA suggesting it is not a potent agonist but a competitive antagonist. In silico analysis indicated TBBPA can be successfully docked into the binding cavity with similar poses but still have AHR-form-specific interactions. Molecular dynamics simulation proved TBBPA can be more flexible than the coplanar ligand TCDD, especially in ccaAHR1b with greater root-mean-square deviation (RMSD), of which TCDD-induced transactivation seemed not to be blocked by TBBPA. This research increased the understanding of TBBPA toxicity and alteration of the AHR pathway, and pointed out the need to perform additional toxicology evaluation of emerging contaminants, especially on non-model species.

TBBPA causes apoptosis in grass carp hepatocytes involving destroyed ER-mitochondrial function

Tetrabromobisphenol A (TBBPA) is the most-produced brominated flame retardant, which can be found in various industrial and household products. Studies have shown that TBBPA has hepatotoxicity, and could pose a risk to aquatic animals. The endoplasmic reticulum (ER) and mitochondria are two important organelles that are highly dynamic in cells, the homeostasis and orchestrated interactions of which are crucial to maintaining cellular function. The aim of this study was to explore the involvement of ER-mitochondria crosstalk in TBBPA-induced toxicity in aquatic animals' hepatocytes. Herein, we exposed grass carp hepatocytes (L8824 cells) to different concentrations of TBBPA. Our experimental results suggested that TBBPA exposure suppressed cell viability and caused apoptosis of L8824 cells. TBBPA treatment upregulated expressions of ER stress markers, increased reactive oxygen species (ROS) and mitochondrial Ca2+ levels, and reduced mitochondrial membrane potential (MMP) in L8824 cells. However, the pretreatment of 2-aminoethoxydiphenyl borate (2-APB) could alleviate TBBPA-induced cell apoptosis, ER stress, and mitochondrial dysfunction. Additionally, 2-APB pretreat relieved ER-mitochondrial contact and the expression of ER-mitochondrial function-related genes induced by high-dose TBBPA. Taken together, these results indicated that TBBPA caused grass carp hepatocyte apoptosis by destroying ER-mitochondrial crosstalk.

Tetrabromobisphenol a and its alternative tetrachlorobisphenol a induce oxidative stress, lipometabolism disturbance, and autophagy in the liver of male Pelophylax nigromaculatus

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) have been widely used as flame retardants. However, their potential health risks to organisms have raised concerns, particularly for liver toxicity. Present study aimed to explore the toxic effects of TCBPA and TBBPA on black-spotted frogs (Pelophylax nigromaculatus) liver oxidative stress, autophagy, and lipid accumulation. After exposure to 0.001, 0.01, 0.1, and 1 mg/L TBBPA and TCBPA for 14 days, the content of cholesterol and triglyceride were significantly elevated. In addition, the malondialdehyde level rose greatly in dose dependent. However, the glutathione level declined in high TBBPA groups (0.01 and 0.1 mg/L). Furthermore, expressions of Beclin1, Atg5, and Atg7 were significantly increased, while p62 was markedly declined, respectively. Results obstained suggested that TBBPA and TCBPA exposure induced liver toxicity in black-spotted frog. This study provided insights into the toxicity mechanism of bisphenol flame retardants in amphibians and will aid in the ecological risk assessment of flame retardants.

Concentrations of Tetrabromobisphenol-A and hexabromocyclododecane in Thai child daycare centre dust and the exposure risk for young children

Children spend one-third of their day in child daycare centres, where they may be exposed to toxic chemicals, such as tetrabromobisphenol-A (TBBPA) and hexabromocyclododecane (HBCDD), from indoor dust. However, studies on the exposure of TBBPA and HBCDD in schools remain scarce, especially in Thailand, where no such study has yet been reported. Therefore, in this study, we collected dust samples from 20 child daycare centres in Thailand and analysed them for flame retardants, TBBPA and HBCDD. TBBPA was detected in all samples with a median concentration of 35 ng g−1 (range, 14–5017.7 ng g−1). The median level of HBCDD was lower than the quantitation limit (LOQ) with <LOQ to 86.6 ng g−1 of dust sample. The electronic density score was calculated from the number of electronic appliances divided by each sampled surface floor area that revealed an abundance of TBBPA in the dust in rooms with many electronic items. The use of electronic devices, especially printers, that were found to be related to the high TBBPA concentration in the room, should be minimised in child daycare centres. The children's exposure to these chemicals from dust was estimated for dust ingestion and dermal absorption. The combined exposure was lower than the established reference dose value, and the hazard quotient for children via these two pathways were ranged 0.7 × 10−6 – 2.7 × 10−4 for TBBPA and 1.8 × 10−5 – 4.9 × 10−5 for HBCDD, which did not exceed 1.0. Although there is uncertainty regarding the potential health effects of long-term exposure to these substances, it is undeniable that child daycare centres represent a source of exposure to these substances for children. Further investigation of other intake routes of several flame retardants in child daycare centres and identification of the sources of these substances is warranted to decrease children's health risks from exposure to these harmful substances in child daycare centres.

TBBPA induced ROS overproduction promotes apoptosis and inflammation by inhibiting autophagy in mice lung

Tetrabromobisphenol A (TBBPA), a non-degradable environmental pollutant, was discharge into the air during the manufacture, use and recycling of plastic products. Respiratory exposure is the main way to inhalation of TBBPA. However, the research on the damage of TBBPA to the respiratory system is still extremely few. The aim of this experiment was to explore the mechanism of TBBPA toxicity to the lungs. Forty C57BL/6 J mice randomly divided into 4 groups, and the experimental groups with TBBPA at 10 n M/kg, 20 n M/kg and 40 n M/kg for 14 consecutive days. Histopathological and ultrastructural analysis showed that the inflammatory cells infiltrated and tissue structure damaged in the lung of mice with exposing to TBBPA. The ROS and MDA levels increase and the T-AOC, GSH-Px, CAT, SOD activities inhibition was found in lung tissue with TBBPA exposure. The expression of autophagy-related factors Beclin-1, P62, LC3-II, ATG5, and ATG7 decreased. The activation of NF-κB/TNF-α pathway indicates the occurrence of inflammation. The expression of Bax, caspase3, caspase7, caspase 9 increase, the expression of Bcl-2 decreased, and the apoptosis pathway activated. The autophagy inducer rapamycin can reverse the adverse effects of inflammation and apoptosis. Taken together, TBBPA inhibits autophagy-induced pneumonia and apoptosis by overproduction ROS.

Growth inhibition of offspring larvae caused by the maternal transfer effects of tetrabromobisphenol A in zebrafish

Tetrabromobisphenol A (TBBPA) is an industrial chemical and the most widely used brominated flame retardant, and has raised environmental health concerns. However, the maternal transfer toxicity of TBBPA is less studied in fish despite its frequency in the water environment, and limited evidence exists to confirm the major contributing factors. In this study, we performed a 28-d experiment on female and male zebrafish exposed to TBBPA (0, 5, 50, and 500 μg/L), and shortened body length of offspring larvae was observed at the maximum exposure concentration. By cross-mating control and exposed zebrafish (male or female), our results showed that the observed growth inhibition in the progeny was attributed to the maternal transfer effect. Although 28-d exposure resulted in the existence of TBBPA in ovaries and ova, the maternal transfer of TBBPA was not responsible for the shortened body length of offspring larvae, as evidenced through TBBPA embryo microinjection. Moreover, proteomic analyses in ova indicated that the abundance of apolipoproteins (apoa1, apoa1b, apoa2, apoa4b, and apoc1) was significantly downregulated in the ova, which may be partially responsible for the shortened body length of offspring larvae. Interestingly, these proteins did not differentially express in the ovaries. Therefore, our results demonstrate that TBBPA exposure disturbed maternal protein transfer from the ovaries to the ova, providing novel insights into the underlying maternal transfer effects.

Tetrabromobisphenol A and hexabromocyclododecanes from interior and surface dust of personal computers: implications for sources and human exposure.

Tetrabromobisphenol A (TBBPA) and hexabromocyclododecane isomers (HBCDs) are widely detected in indoor environments, but the research on the accumulation, contamination, and human exposure of TBBPA and HBCDs in electronic products dust is still limited. It is unclear whether electronic products might pose human health risk via dust ingestion and dermal absorption. In this study, the levels and distributions of TBBPA and HBCDs were investigated in the personal computer (PC) interior dust and PC surface (upper and bottom) wipes. The median concentrations of TBBPA in PC interior dust, upper, and bottom surface wipes were 168.1ng/g, 13.2ng/m2, and 15.2ng/m2, respectively. These levels were generally higher than those of HBCDs, which were 95.2ng/g, 11.7ng/m2, and 12.3ng/m2, respectively. No significant correlations were found among the PC upper and bottom surface wipes, and interior dust, indicating different sources of TBBPA and HBCDs in PC interior and surface dust. The TBBPA and HBCDs in the PC interior dust were mainly released from inner PC materials, while the sources of target compounds on the surface wipes were likely from external environments. The exposure values of two occupational populations (including PC owners and PC repair workers) to TBBPA and HBCDs were measured by PC interior dust and upper surface wipes. The results imply dust ingestion (including hand-to-mouth uptake) is the main contributor of the exposure route to TBBPA and HBCDs for both PC owners and repair workers. Compared to PC owners, PC repair workers showed the greater risk in exposure assessment, which should be paid more attention.

Abscisic acid plays a key role in the mechanism of photosynthetic and physiological response effect of Tetrabromobisphenol A on tobacco

The toxicity of bromide to animals and microorganisms has been widely studied, but the mechanism by which bromide toxicity affects plants is rarely studied. This study used the bromophenol compound Tetrabromobisphenol A (TBBPA) as a representative of bromide to explore the physiological and molecular response mechanism of tobacco leaves to TBBPA. In addition, physiological determination, transcriptomics, weighted gene co-expression network analysis (WGCNA) analysis, and random forest prediction model were conducted. The findings from this study indicated that TBBPA limited the photoreaction process by destroying the light-catching antenna protein of tobacco leaves, the activity of the photosystem reaction centers (PSII and PSI), and the linear electron transport efficiency. TBBPA also reduced the rate of the Calvin-Benson cycle by inhibiting the activities of gene such as Rubisco, PGK, and TPI, and finally destroyed the photosynthesis process. Although cyclic electron transport was enhanced under stress conditions, it could not reverse the damage caused by TBBPA on photosynthesis. TBBPA exposure resulted in the accumulation of reactive oxygen species (ROS) in tobacco leaves, and the activities of Superoxide dismutase (SOD), Ascorbate peroxidase (APX), and Glutathione peroxidase (GPX) and their coding genes were significantly down-regulated. Although POD activity and proline (Pro) content were increased, they were insufficient to remove excess O2·- free radicals to relieve ROS stress. WCGNA and random forest models predicted that the damage of TBBPA to the above processes in tobacco was closely related to the increase in abscisic acid (ABA) content. TBBPA affects the Calvin cycle by inducing ABA signal transduction and stomatal closure, which leads to a series of chain reactions, such as electron transport chain obstruction, excess of ROS, decrease in chlorophyll synthesis, and photosystem reaction center damage.

Eucalyptol antagonized the apoptosis and immune dysfunction of grass carp hepatocytes induced by tetrabromobisphenol A by regulating ROS/ASK1/JNK pathway.

Tetrabromobisphenol A (TBBPA) is a common environmental pollutant which has multi-organ toxicity to mammals. Eucalyptol (EUC) has super antioxidant biological activity. However, in this experimental study, we probed into the mechanism of toxic of TBBPA exposure on Grass carp hepatocytes (L8824 cells) and the antagonistic impact of EUC on TBBPA. We treated L8824 cells with 8μg/ml TBBPA and/or 20 μM EUC for 24 h in this test research. The experiment results suggested that TBBPA exposure induced elevated levels of reactive oxygen species (ROS), led to oxidative stress, decreased SOD and CAT activities, decreased GSH and T-AOC contents, exacerbated MDA accumulation, activated ASK1/JNK signaling pathway, and further increased the contents of mitochondrial dependent apoptosis pathway related indicators (Cyt-C, Bax, Caspase 9, Caspase 3), while Bcl-2 expression decreased. In addition, TBBPA exposure induced increased expression of TNF-α, IL-6, IL-1β, and decreased expression of IL-2, IFN-γ, Hepcidin, β-defensin, LEAP2. The oxidative stress level, ASK1/JNK signal pathway expression level, apoptosis ratio and cellular immune function of cells exposed to EUC alone did not change significantly. Combined exposure of TBBPA and EUC significantly reduced the proportion of apoptosis and restored cellular immune function. Therefore, these results suggest that EUC can effectively antagonize TBBPA-induced apoptosis and immune dysfunction of L8824 cells by regulating ROS/ASK1/JNK signaling pathway.

The joint effects of nanoplastics and TBBPA on neurodevelopmental toxicity in Caenorhabditis elegans.

Both of nanoplastics (NPs) and Tetrabromobisphenol A (TBBPA) are organic pollutants widely detected in the environment and organisms. The large specific surface area of NPs makes them ideal vectors for carrying various toxicants, such as organic pollutants, metals, or other nanomaterials, posing potential threats to human health. This study used Caenorhabditis elegans (C. elegans) to investigate the neurodevelopmental toxicity induced by combined exposure of TBBPA and polystyrene NPs. Our results showed that combined exposure caused synergistic inhibitory effects on the survival rate, body length/width, and locomotor ability. Furthermore, the overproduction of reactive oxygen species (ROS), lipofuscin accumulation, and dopaminergic neuronal loss suggested that oxidative stress was involved in induction of neurodevelopmental toxicity in C. elegans. The expressions of Parkinson's disease related gene (pink-1) and Alzheimer's disease related gene (hop-1) were significantly increased after combined exposure of TBBPA and polystyrene NPs. Knock out of pink-1 and hop-1 genes alleviated the adverse effects such as growth retardation, locomotion deficits, dopaminergic loss, and oxidative stress induction, indicating that pink-1 and hop-1 genes play an important role in neurodevelopmental toxicity induced by TBBPA and polystyrene NPs. In conclusion, TBBPA and polystyrene NPs had synergistic effect on oxidative stress induction and neurodevelopmental toxicity in C. elegans, which was mediated through increased expressions of pink-1 and hop-1.

TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination

Tetrabromobisphenol A (TBBPA) and its derivatives widely exist in various environments and biota. Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer (EC), the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear. The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC, and the crucial mechanism on the progression of EC caused by bromine flame retardants exposure. In this research, TBBPA and two of the most common TBBPA derivatives including TBBPA bis (2-hydroxyethyl ether) (TBBPA-BHEE) and TBBPA bis (dibromopropyl ether) (TBBPA-BDBPE) were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model. Under environmental concentrations, TBBPA promoted the proliferation of EC, the main derivatives of TBBPA (TBBPA-BHEE and TBBPA-BDBPE) did not present the similar facilitation effects. The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation, which resulted in the increase of downstream cell cycle and decrease of apoptosis. The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome. This finding revealed the effects of TBBPA and its derivatives on EC proliferation, thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

Selenium mitigates the inhibitory effect of TBBPA on NETs release by regulating ROS/MAPK pathways-induced carp neutrophil apoptosis and necroptosis

Tetrabromobisphenol A (TBBPA) is one of the most common and persistent organic pollutants found in the environment. When TBBPA is ingested by organisms through various pathways and stored in the body, it shows obvious harmful effects. Selenium (Se) works as an antioxidant in the body, allowing it to withstand the poisonous effects of dangerous substances. The effects and mechanisms of Se and TBBPA on carp neutrophil immune function, apoptosis, and necroptosis, however, are unknown. As a result, we created TBBPA exposure and Se antagonism models using carp neutrophils as study objects, and we investigated the expression of genes implicated in extracellular traps (NETs), cytokines, apoptosis, and necroptosis. The findings demonstrated that extracellular traps neutrophils in the TBBPA group displayed the inhibition of NETs, apoptosis, and necrosis, as well as an increase in Reactive oxygen species (ROS) levels and activation of the MAPK pathway. The expression of genes related to the mitochondrial apoptosis pathway (Bax, Cyt-c, Bcl-2 and Caspase-3) and necroptosis pathway (MLKL, RIPK1, RIPK3, Caspase-8 and FADD) were activated. The expression of inflammatory factors IL-1 and TNF-α were increased, and the expression of IL-2 and IFN-γ were decreased. But an appropriate concentration of Se can mitigate the effects of TBBPA. Our results suggest that Se can mitigate the inhibitory effect of TBBPA on NETs release by regulating apoptosis and necroptosis of carp neutrophil via ROS/MAPK pathways. These results provide a basis information for exploring the toxicity of TBBPA, and enrich the anti-toxicity mechanism of trace element Se in the body.