RESUMO
Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE) is the major TBBPA derivative. It has been detected in different environmental samples. Previous studies show that TBBPA-DHEE caused neurotoxicity in rats. In this study, juvenile zebrafish were exposed to various concentrations of TBBPA-DHEE to ascertain the potential neurotoxicity of TBBPA-DHEE, the chemical, and its possible molecular mechanism of action. Behavioral analysis revealed that TBBPA-DHEE could significantly increase the swimming distance and speed in the 1.5 mg/L group compared to the control. In contrast, the swimming distance and speed were significantly reduced in the 0.05 and 0.3 mg/L groups, affecting learning, memory, and neurodevelopment. Similarly, TBBPA-DHEE exposure caused a concentration-dependent significant increase in the levels of excitatory neurotransmitters, namely, dopamine, norepinephrine, and epinephrine, which could be attributed to the change observed in zebrafish behavior. This demonstrates the neurotoxicity of TBBPA-DHEE on juvenile zebrafish. The concentration-dependent increase in the IBR value revealed by the IBR index reveals the noticeable neurotoxic effect of TBBPA-DHEE. Transcriptomic analysis shows that TBBPA-DHEE exposure activated the PPAR signaling pathways, resulting in a disturbance of fatty acid (FA) metabolism and changes in the transcript levels of genes involved in these pathways, which could lead to lipotoxicity and hepatotoxicity. Our findings demonstrate a distinct endocrine-disrupting response to TBBPA-DHEE exposure, possibly contributing to abnormal behavioral alterations. This study provides novel insights into underlying the mechanisms and effects of TBBPA-DHEE on aquatic organisms, which may be helpful forenvironmental/human health risk assessments of the emerging pollutant.
Assuntos
Retardadores de Chama , Peixe-Zebra , Humanos , Ratos , Animais , Peixe-Zebra/metabolismo , Éteres/análise , Éteres/metabolismo , Análise de Sequência de RNA , Retardadores de Chama/toxicidade , Retardadores de Chama/análise , Retardadores de Chama/metabolismoRESUMO
BFRs (brominated flame retardants) are a class of compounds that are added to or applied to polymeric materials to avoid or reduce the spread of fire. Tetrabromobisphenol A (TBBPA) is one of the known BFR used many in industries today. Due to its wide application as an additive flame retardant in commodities, TBBPA has become a common indoor contaminant. Recent researches have raised concerns about the possible hazardous effect of exposure to TBBPA and its derivatives in humans and wildlife. This review gives a thorough assessment of the literature on TBBPA and its derivatives, as well as environmental levels and human exposure. Several analytical techniques/methods have been developed for sensitive and accurate analysis of TBBPA and its derivatives in different compartments. These chemicals have been detected in practically every environmental compartment globally, making them a ubiquitous pollutant. TBBPA may be subject to adsorption, biological degradation or photolysis, photolysis after being released into the environment. Treatment of TBBPA-containing waste, as well as manufacturing and usage regulations, can limit the release of these chemicals to the environment and the health hazards associated with its exposure. Several methods have been successfully employed for the treatment of TBBPA including but not limited to adsorption, ozonation, oxidation and anaerobic degradation. Previous studies have shown that TBBPA and its derivative cause a lot of toxic effects. Diet and dust ingestion and have been identified as the main routes of TBBPA exposure in the general population, according to human exposure studies. Toddlers are more vulnerable than adults to be exposed to indoor dust through inadvertent ingestion. Furthermore, TBBP-A exposure can occur during pregnancy and through breast milk. This review will go a long way in closing up the knowledge gap on the silent and over ignored deadly effects of TBBPA and its derivatives and their attendant consequences.
Assuntos
Poluentes Ambientais , Retardadores de Chama , Bifenil Polibromatos , Adulto , Poeira/análise , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Retardadores de Chama/análise , Retardadores de Chama/toxicidade , Humanos , Bifenil Polibromatos/análise , Bifenil Polibromatos/toxicidadeRESUMO
Tetrabromobisphenol A bis (2- hydroxyethyl) ether (TBBPA-DHEE), as one of the main derivatives of Tetrabromobisphenol A, been attracted attention for its health risks. In this study, the neurotoxicity, mechanism, and susceptivity of TBBPA-DHEE exposure to sexually developing male rats were systematically studied. Neurobehavioral research showed that TBBPA-DHEE exposure could significantly affect the behavior, learning,and memory abilities of male-developing rats, and aggravate their depression. TBBPA-DHEE exposure could inhibit the secretion of neurotransmitters. Transcriptomics studies show that TBBPA-DHEE can significantly affect gene expression, and a total of 334 differentially expressed genes are enriched. GO function enrichment analysis shows that TBBPA-DHEE exposure can significantly affect the expression of genes related to synapses and cell components. KEGG function enrichment analysis shows that TBBPA-DHEE exposure can significantly affect the expression of signal pathways related to nerves, nerve development, and signal transduction. Susceptibility analysis showed that female rats were more susceptible to TBBPA-DHEE exposure than male rats. Therefore, TBBPA-DHEE exposure has neurodevelopmental toxicity to male developmental rats, and female developmental rats are more susceptible than male developmental rats. Its possible molecular mechanism is that TBBPA-DHEE may inhibit the secretion of neurotransmitters and affect signal pathways related to neurodevelopment and signal transduction.
Assuntos
Retardadores de Chama , Bifenil Polibromatos , Feminino , Masculino , Ratos , Animais , Éter , Ratos Sprague-Dawley , Éteres , Bifenil Polibromatos/toxicidade , Bifenil Polibromatos/análise , Etil-Éteres , Neurotransmissores , Retardadores de Chama/toxicidade , Retardadores de Chama/análiseRESUMO
TBBPA bis(2-hydroxyethyl) ether (TBBPA-DHEE), one of the main derivatives of TBBPA, has been widely detected in environmental samples and been discovered to be potential neurotoxic. In this study, the juvenile zebrafish were selected as the research subject to explore the neurotoxicity and its mechanism of low-dose TBBPA-DHEE exposure, and to reveal the neurotoxicity susceptibility in different sexes. Behavioral studies revealed that TBBPA-DHEE could significantly reduce the swimming velocity, maximum acceleration and cumulative duration of high-speed mobility, significantly increasing the cumulative duration of low-speed mobility and average social distance. It significantly reduced the contents of ATP, glutamate and Ca2+ in the whole brain. The histopathological study demonstrated that TBBPA-DHEE could cause brain tissue damage in female and male juvenile zebrafish. The comprehensive data analysis indicated that female zebrafish were more susceptible to TBBPA-DHEE exposure than male zebrafish. Transcriptomic analysis showed that TBBPA-DHEE could significantly affect the expressions of behavioral and development-related genes. Furthermore, female and male juvenile zebrafish have different molecular mechanisms of neurotoxicity. For female juvenile zebrafish, the potential mechanism of neurotoxicity could be that it interfered with the feedback regulation of nerves by affecting the related genes expressions in the signaling pathways such as Ca2+ signaling, Wnt signaling and synapses. For male juvenile zebrafish, the potential mechanism of neurotoxicity may be through affecting the expression of related genes in hormones and neuro-related genes. This research could reveal the potential neurotoxicity of TBBPA-DHEE to aquatic organisms, which will be helpful to reveal the health effects of the emerging environmental pollutants.
Assuntos
Retardadores de Chama , Bifenil Polibromatos , Animais , Feminino , Masculino , Peixe-Zebra/genética , Éter , Éteres/análise , Etil-Éteres , Bifenil Polibromatos/toxicidade , Bifenil Polibromatos/análise , Retardadores de Chama/toxicidadeRESUMO
Endocrine-disrupting chemicals (EDCs) are now ubiquitously distributed in the environment. Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE) pollution in environment media poses a significant threat to humans and aquatic organisms as a result of its potential neurotoxicity and endocrine-disrupting effect. The endocrine-disrupting effects of TBBPA-DHEE on aquatic organisms, however, have received limited attention. In this study, the neurotoxicity and reproductive endocrine-disruptive effect of TBBPA-DHEE was evaluated by observing the neurobehavioral changes, vitellogenin (VTG), testosterone, 17ß-estradiol and gene expression levels in adult male and female zebrafish exposed to TBBPA-DHEE (0.05, 0.2 and 0.3 mg/L) for 100 days. Furthermore, transcriptomic analysis was conducted to unravel other potential neuroendocrine-disrupting mechanism. Our result showed TBBPA-DHEE significantly (p < 0.05) altered the locomotor behavior and motor coordination abilities in both sexes. Steroid hormone and VTG levels were also altered indicating the neuroendocrine-disrupting effect of TBBPA-DHEE on the hypothalamic-pituitary-gonadal-axis. A total of 1568 genes were upregulated and 542 genes downregulated in males, whereas, 1265 upregulated and 535 downregulated genes were observed in females. The KEGG enrichment analysis showed that cell cycle and p55 signaling pathways were significantly enriched due to TBBPA-DHEE exposure. These pathways and its component genes are potential target of EDCs. The significant upregulation of genes in these pathways could partly explain the neuroendocrine disrupting effect of TBBPA-DHEE. The observed toxic effects of TBBPA-DHEE observed in this study is confirmation of the endocrine-disrupting toxicity of this chemical which would be valuable in biosafety evaluation and biomonitoring of TBBPA-DHEE for public health purposes.
Assuntos
Bifenil Polibromatos , Poluentes Químicos da Água , Animais , Humanos , Feminino , Masculino , Peixe-Zebra/genética , Éter , Transcriptoma , Éteres/análise , Etil-Éteres , Bifenil Polibromatos/toxicidade , Bifenil Polibromatos/análise , Bifenil Polibromatos/química , Sistemas Neurossecretores , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análiseRESUMO
TBBPA bis(2-hydroxyethyl) ether (TBBPA-DHEE) pollution in the environment has raised serious public health concerns due to its potential neuroendocrine-disrupting effects. The neuroendocrine-disrupting effects of TBBPA-DHEE on marine spices, on the other hand, have received little attention. The behavioral, neuroendocrine-disrupting, and possible reproductive toxicity of TBBPA-DHEE were assessed in sexual developing zebrafish treated for 40 days by examining locomotor activity, Gonadotrophin releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels, and quantifying gene expression. In addition, transcriptome profiling was carried out to explore the possible mechanisms. According to our findings, TBBPA-DHEE treated zebrafish showed altered locomotor activity, a potential neuroendocrine-disrupting effect via the toxic effect on the hypothalamus and pituitary gland, which is evident in decreased levels of GnRH, FSH, and LH, according to our findings. The transcriptomic profiling reveals that a total of 216 DEGs were detected (5 upregulated and 211 down-regulated). Transcriptomic analysis shows that TBBPA-DHEE exposure caused decreased transcript levels of genes (cyp11a1, ccna1, ccnb2, ccnb1, cpeb1b, wee2) involved in cell cycle oocyte meiosis, progesterone mediated oocyte maturation, and ovarian steroidogenesis, which are known reproduction-related pathways. Overall, these findings add to our understanding of the impact of TBBPA-DHEE and biomonitoring in the maritime environment.
Assuntos
Desenvolvimento Sexual , Peixe-Zebra , Animais , Hormônio Liberador de GonadotropinaRESUMO
Tetrabromobisphenol A bis (2-hydroxyethyl ether) (TBBPA-DHEE) is a derivative of Tetrabromobisphenol A (TBBPA) used as an intermediate flame retardant in engineering polymers. The mechanism of neurodevelopmental toxicity of TBBPA-DHEE remains unclear due to limited toxicological data. We performed behavioral and transcriptomic analyses to assess the neurodevelopmental effects of TBBPA-DHEE on developing zebrafish and potential toxicity mechanisms. Our result shows that exposure to TBBPA-DHEE significantly increased mortality, deformity rate, and reduction in hatch rate, hatchability, and body length relative to the DMSO control. The behavior analysis indicates that TBBPA-DHEE significantly reduced the spontaneous movement of larva compared to the control. The TSH and GH levels were significantly reduced in all the exposure groups in a concentration-dependent manner relative to the DMSO control. TBBPA-DHEE exhibited a significant reduction in locomotor activity across all the exposure groups in the light/dark locomotion test. The transcriptomic analysis result shows that 579 genes were differentially expressed. KEGG analysis shows the enrichment of complement cascade, JAK-STAT signaling pathway, cytokine-cytokine interaction, and phototransduction pathway resulting in a change in mRNA expression of their genes. These observed changes in developmental endpoints, hormonal level, and alteration in mRNA expression of component genes involved in neurodevelopmental pathways could be part of the possible mechanism of the observed toxic effects of TBBPA-DHEE exposure on zebrafish. This study could reveal the possible neurodevelopmental toxicity of TBBPA-DHEE to aquatic species, which could help uncover the health implications of emerging environmental contaminants.
Assuntos
Retardadores de Chama , Bifenil Polibromatos , Poluentes Químicos da Água , Animais , Citocinas/metabolismo , Dimetil Sulfóxido/metabolismo , Éter/metabolismo , Éteres/análise , Éteres/metabolismo , Retardadores de Chama/toxicidade , Bifenil Polibromatos/análise , Bifenil Polibromatos/metabolismo , Bifenil Polibromatos/toxicidade , Polímeros , RNA Mensageiro/metabolismo , Tireotropina/genética , Tireotropina/metabolismo , Transcriptoma , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
Tetrabromobisphenol A bis(2-hydroxyetyl) ether (TBBPA-DHEE) is among the main derivatives of Tetrabromobisphenol A (TBBPA). Result from previous study showed that TBBPA-DHEE can cause neurotoxicity in rat. In this study, zebrafish larvae were used for evaluation of TBBPA-DHEE-induced developmental toxicity, apoptosis, oxidative stress and the potential molecular mechanisms of action. Our result showed that TBBPA-DHEE exposure caused a significant concentration-dependent developmental toxicity endpoints like death rate, malformation rate, growth rate. TBBPA-DHEE altered locomotor and enzymes activities of larvae and caused apoptosis within the brain indicating the potential TBBPA-DHEE-induced cardiac, brain impairment in the zebrafish larvae. Our transcriptomic analysis shows that 691 genes were differentially expressed (DEGs) (539 upregulated, 152 downregulated). The KEGG and GO enrichment pathway analysis shows that the DEGs were involved in development, immunity, enzyme activity. Our study provides novel evidence on the neurodevelopmental toxicity and toxicity mechanism of TBBPA-DHEE which are vital for assessment of the environmental toxicity and risk assessment of the chemical.