Combined toxic impact of polystyrene nanoplastics and a flame retardant tetrabromobisphenol A (TBBPA) on freshwater algae Scenedesmus obliquus

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.

Tetrabromobisphenol A (TBBPA), one of the most widely used global brominated flame retardants, is used to improve fire safety of laminates in electrical and electronic equipment. To investigate the nephrotoxic potential of TBBPA and its toxicokinetic profile in rats, single-dose and daily 14-d repeated-dose toxicity studies at 200, 500, or 1000 mg/kg were performed. Several biochemical parameters were analyzed to evaluate nephrotoxicity of TBBPA. High-dose 1000 mg/kg TBBPA significantly elevated renal thiobarbituric acid-reactive substance (TBARS) levels, and superoxide dismutase (SOD) activity was increased at all 3 doses administered. This was associated with no change in the activity of catalase (CAT). Our results suggest that acute 1-d high-dose administration of TBBPA produced transient renal changes at 5 h. Subsequently, TBBPA in serum, urine, and kidney was determined by liquid chromatography–mass spectroscopy (LC/MS). Toxicokinetic studies indicated that TBBPA shows relatively a short half-life (7–9 h) and was eliminated almost completely in feces by 2 d. Based on the results from the 14-d repeated-dose study, TBBPA did not accumulate in the rat, and was eliminated in feces. The present results suggested that TBBPA may not be toxic to kidney, as the chemical is not bioavailable and is not present in renal tissue.

Using primary cultures of rat cerebellar granule cells (CGC) we examined the role of calcium transients induced by tetrabromobisphenol A (TBBPA) in triggering oxidative stress and cytotoxicity. CGC were exposed for 30 min to 10 or 25 µM TBBPA. Changes in intracellular calcium concentration ([Ca2+]i), in the production of reactive oxygen species (ROS), and in the potential of mitochondria (∆Ψm) were measured fluorometrically during the exposure. The intracellular glutathione (GSH) and catalase activity were determined after the incubation; cell viability was evaluated 24 h later. TBBPA concentration-dependently increased [Ca2+]i and ROS production, and reduced GSH content, catalase activity, ∆Ψm and neuronal viability. The combination of NMDA and ryanodine receptor antagonists, MK-801 and bastadin 12 with ryanodine, respectively, prevented Ca2+ transients and partially reduced cytotoxicity induced by TBBPA at both concentrations. The antagonists also completely inhibited oxidative stress and depolarization of mitochondria evoked by 10 µM TBBPA, whereas these effects were only partially reduced in the 25 µM TBBPA treatment. Free radical scavengers prevented TBBPA-induced development of oxidative stress and improved CGC viability without having any effect on the rises in Ca2+ and drop in ∆Ψm. The co-administration of scavengers with NMDA and ryanodine receptor antagonists provided almost complete neuroprotection. These results indicate that Ca2+ imbalance and oxidative stress both mediate acute toxicity of TBBPA in CGC. At 10 µM TBBPA Ca2+ imbalance is a primary event, inducing oxidative stress, depolarization of mitochondria and cytotoxicity, whilst at a concentration of 25 µM TBBPA an additional Ca2+-independent portion of oxidative stress and cytotoxicity emerges.

Tetrabromobisphenol A (TBBPA) is a high-production chemical widely used in printed circuit boards and other polymeric materials for inflaming. As an environmental pollutant, it is widely found in various abiotic and biological media. Usually, the TBBPA could enter the body through skin contact, respiratory exposure and the dietary intake, among which respiratory exposure may be a most important exposure route. Previous studies reported that TBBPA possesses the endocrine, liver and kidney toxicity. However, few studies focused on the effects of TBBPA on respiratory toxicity. Therefore, it is urgent to study the toxic effects of TBBPA on respiratory system. In this study, human bronchial cells Beas2B and pulmonary epithelial cells 16HBE were used as subjects to study the exposure toxicity of TBBPA. Firstly, the viability and permeability of cells were assayed during the TBBPA exposure process. When TBBPA was in low concentration range (0−0.4 μmol/L), 24 h of exposure cannot significantly affect cell viability. When concentration of TBBPA was greater than 10 μmol/L, the inhibitory effect on cell activity was obviously observed. When concentration of TBBPA was up to 50 μmol/L, the cell viabilities of 16HBE and Beas2B cells decreased to 80.9% and 86.2%. It is worth noting that, as compared with bronchial epithelial cell 16HBE, lung epithelial cell Beas2B has a higher tolerance to TBBPA, which may be due to the different cell structures. In addition, the oxidation stress of cells was also determined by assaying the cell intracellular reactive oxygen species (ROSs), antioxidant enzymatic activity of superoxide dismutase (SOD) and catalase (CAT) during the whole expose duration. The results showed that the levels of intracellular ROSs obviously increased in both cells, indicating that peroxidation occurred in the cells during TBBPA exposure. Correspondingly, the enzymatic activities of SOD and CAT also increased, indicating that oxidative stress happened in cells. After that, flow cytometry was applied to analyze cell apoptosis. The results showed that partial apoptosis occurred after 24 h of TBBPA exposure, indicating that TBBPA could induce cell apoptosis. Besides, with the increase of exposure concentration, the apoptosis rate of the two kinds of cells also increased. Furthermore, the q-PCR was used to determine the apoptosis-related gene expression. The results revealed that the expression levels of apoptosis-related genes p53, Survivin , bax , bcl-2 , caspase-3 , caspase-9 were all up-regulated to different degrees, further confirming that cells were apoptotic caused by TBBPA. Further, compared with the 12-h exposure data, 24-h exposure would stimulate more intense expression up-regulation. In all, this research mainly investigated the toxicity of typical generation bromide flame retardants TBBPA on human bronchial epithelial cells 16 HBE and lung epithelial cells Beas2B. Results showed that the exposure of TBBPA could cause damage to cell viability and elicit oxidative stress in cells, which could further induce cell apoptosis. The results of cytotoxicity related to human respiratory system in this work can provide a scientific basis for revealing the health risk of toxic organic pollutants to human respiratory system.

Identification and quantification of TBBPA and its metabolites in adult zebrafish by high resolution liquid chromatography tandem mass spectrometry

Breast adipose metabolites mediates the association of tetrabromobisphenol a with breast cancer: A case-control study in Chinese population

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

Microplastics (MPs) and nanoplastics (NPs) in the environment pose significant risks to organisms of different trophic levels. While the toxicity of MPs and NPs have been extensively investigated, it remains unknown whether these particles affect microbial transformation of organic pollutants. Here, we show that 20 and 100 nm polystyrene NPs (PS-NPs) can inhibit the transformation of tetrabromobisphenol A (TBBPA) by Gram-positive bacterium Rhodococcus jostii in a concentration-dependent manner. We found that smaller PS-NPs were more inhibitory than larger ones and that both PS-NPs affected biotransformation in several ways. PS-NPs adsorbed TBBPA on their surface and reduced the bioavailable concentration of TBBPA for transformation by R. jostii. Furthermore, PS-NPs induced oxidative stress, increased membrane permeability, and downregulated O-methyltransferase enzymes that transform TBBPA into their methylated derivatives. Our results demonstrate that PS-NPs can impact microbial transformation of organic pollutants, and these effects should be accounted for in future environmental risk assessments.

Tetrabromobisphenol A disturbs zinc homeostasis in cultured cerebellar granule cells: A dual role in neurotoxicity

TBBPA caused multiple intestinal injuries via ROS/NF-κB signal in common carp

ABSTRACTThis study was undertaken to investigate the possible involvement of oxidative stress in tetrabromobisphenol A (TBBPA)-induced toxicity in osteoblastic MC3T3-E1 cells. To examine the potential effect of TBBPA on cultured osteoblastic cells, we measured cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, cardiolipin content, cytochrome c release, cyclophilin levels, and differentiation markers in osteoblastic MC3T3-E1 cells. TBBPA exposure for 48 h caused the apoptosis and cytotoxicity of MC3T3-E1 cells. TBBPA also induced ROS and mitochondrial superoxide production in a concentration-dependent manner. These results suggest that TBBPA induces osteoblast apoptosis and ROS production, resulting in bone diseases. Moreover, TBBPA induced cardiolipin peroxidation, cytochrome c release, and decreased ATP levels which induced apoptosis or necrosis. TBBPA decreased the differentiation markers, collagen synthesis, alkaline phosphatase activity, and calcium deposition in cells. Additionally, TBBPA decreased cyclophilin A and B releases. Taken together, these data support the notion that TBBPA inhibits osteoblast function and has detrimental effects on osteoblasts through a mechanism involving oxidative stress and mitochondrial dysfunction.

Tetrabromobisphenol A (TBBPA) is extensively utilized as a brominated flame retardant in numerous chemical products. As an environmental contaminant, the potential human toxicity of TBBPA has been attracting increasing attention. Nonetheless, the exact underlying mechanisms of toxicological effects caused by TBBPA remain uncertain. In this study, we investigated the potential mechanisms of TBBPA toxicity in vitro in the A549 cell line, one of the widely used type II pulmonary epithelial cell models in toxicology research. Cell viability was determined after treatment with varying concentrations of TBBPA. Liquid chromatography-mass spectrometry (LC-MS) metabolomics and metabolic flux approaches were utilized to evaluate metabolite and tricarboxylic acid (TCA) cycle oxidative flux changes. Our findings demonstrated that TBBPA significantly reduced the viability of cells and attenuated mitochondrial respiration in A549 cells. Additionally, LC-MS data showed significant reductions in TCA cycle metabolites including citrate, malate, fumarate, and alpha-ketoglutarate in 50 μM TBBPA-treated A549 cells. Metabolic flux analysis indicated reduced oxidative capacity in mitochondrial metabolism following TBBPA exposure. Moreover, diverse metabolic pathways, particularly alanine, aspartate, and glutamate metabolism and the TCA cycle, were found to be dysregulated. In total, 12 metabolites were significantly changed (p< .05) in response to 50 μM TBBPA exposure. Our results provide potential biomarkers of TBBPA toxicity in A549 cells and help elucidate the molecular mechanisms of pulmonary toxicity induced by TBBPA exposure.

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

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant (BFR) that has frequently been detected in various environmental compartments. Although TBBPA biotransformation has been observed under both aerobic and anaerobic conditions, knowledge of the detailed mechanism of direct aerobic TBBPA biodegradation still remains limited. In this study, the underlying mechanism of cometabolic degradation of TBBPA by Pseudomonas sp. fz under aerobic conditions was investigated. Two key degradation pathways (beta scission and debromination) were proposed based on triple quadrupole liquid chromatography-mass spectrometry (LC-MS) analysis. TBBPA degradation by strain fz was demonstrated to be an extracellular process associated with the low-molecular-mass component (LMMC). Moreover, LMMC was preliminarily identified as oligopeptides, mainly consisting of glycine, proline, and alanine in a 2:1:1 molar ratio. Quenching studies suggested the involvement of hydroxyl radicals ((•)OH) in extracellular TBBPA degradation. To the best of our knowledge, we provide the first evidence that TBBPA was degraded by a biogenic Fenton-like reaction mediated via extracellular H2O2 and Fe(II)-oligopeptide complexes by the genus Pseudomonas. This study provides a new insight into the fate and biodegradation of TBBPA and other organic pollutants in natural and artificial bioremediation environments.

TBBPA induces inflammation, apoptosis, and necrosis of skeletal muscle in mice through the ROS/Nrf2/TNF-α signaling pathway