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1.
Chemosphere ; 261: 127705, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32731020

RESUMO

Brominated flame retardants (BFRs) are the compounds used in the industry in order to decrease flammability of various everyday products. The use of BFRs leads to migration of these substances into the environment, which results in the exposure of humans to their action. Although BFRs are widespread in human surrounding, the effect of these compounds on human body has been very poorly assessed. The purpose of this study was to evaluate cytotoxic effects as well as oxidative potential of selected bromophenolic flame retardants such as tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) on human peripheral blood mononuclear cells (PBMCs) that are crucial for proper functioning of the immune system. The cells were treated with the substances studied in the concentrations ranging from 0.0001 to 100 µg/mL for 1 h or 24 h. The results have shown that the compounds examined reduced PBMCs viability and ATP level as well as increased reactive oxygen species (including hydroxyl radical) formation. Moreover, the substances tested induced lipid peroxidation and caused oxidative damage to proteins in the incubated cells. It has also been noticed that the greatest changes were provoked by tetrabromobisphenol A, while the weakest by TBBPS, which is used as a substitute of TBBPA in the manufacture.


Assuntos
Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Halogenação , Humanos , Leucócitos Mononucleares , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fenóis , Espécies Reativas de Oxigênio/metabolismo
2.
Environ Toxicol ; 35(11): 1202-1211, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32621570

RESUMO

Polybrominated diphenyl ethers (PBDEs) are ubiquitous and prolific contaminant in both the abiotic and biotic environment because of the wide industrial applications of these chemicals. In the present study, the effects of 2,2',4,4'-tetrabrominateddiphenyl ether (BDE-47) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153) exposure on the induction of hepatic oxidative stress, DNA damage, and the expression of apoptosis-related genes in adult zebrafish were investigated. The activities of antioxidant enzymes, such as catalase and superoxide dimutase, significantly increased when adult zebrafish was exposed to various concentrations of BDE-47 and BDE-153 for 7 and 15 days. BDE-47 and BDE-153 elicited significant alterations in zebrafish 7-Ethoxyresorufin-O-deethylase activity at 3, 7, or 15 days of exposure. In addition, the significant increase in comet assay parameters of zebrafish hepatocytes in a concentration-dependent manner indicated BDE-47 and BDE-153 induced DNA damage, probably due to observed oxidative stress. Furthermore, a monotonically upregulation of p53 and Caspase3, which are apoptotic-regulated genes, and decreased expression ratio of the anti-apoptotic B-cell lymphoma/leukaemia-2 and Bcl2-associated X protein genes for all BDE-47 and BDE-153 treatments at 7 and 15 days indicated apoptosis induction in zebrafish liver. Our findings help elucidate the mechanisms of BDE-47- and BDE-153-induced toxicity in zebrafish hepatocytes.


Assuntos
Éteres Difenil Halogenados/toxicidade , Bifenil Polibromatos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3 , Ensaio Cometa , Citocromo P-450 CYP1A1/metabolismo , Dano ao DNA , Éteres Difenil Halogenados/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/metabolismo
3.
Chemosphere ; 255: 126919, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32402876

RESUMO

The predominant reliance on bromated flame retardants (BFRs) is diminishing with expanded use of alternative organophosphate flame retardants. However, exposure related issues for susceptible populations, the developing, infirmed, or aged, remain given environmental persistence and home-environment detection. In this regard, reports of flame retardant (FR)-related effects on the innate immune system suggest process by which a spectrum of adverse health effects could manifest across the life-span. As representative of the nervous system innate immune system, the current study examined changes in microglia following exposure to representative FRs, pentabromophenol (PBP), tetrabromobisphenol A (2,2',6,6',-tetrabromo-4,4'-isopropylidine diphenol; TBBPA) and triphenyl phosphate (TPP). Following 18hr exposure of murine BV-2 cells, at dose levels resulting in ≥80% viability (10 and 40 µM), limited alterations in pro-inflammatory responses were observed however, changes were observed in mitochondrial respiration. Basal respiration was altered by PBP; ATP-linked respiration by PBP and TBBPA, and maximum respiration by all three FRs. Basal glycolytic rate was altered by PBP and TBBPA and compensatory glycolysis by all three. Phagocytosis was decreased for PBP and TBBPA. NLRP3 inflammasome activation was assessed using BV-2-ASC (apoptosis-associated speck-like protein containing a CARD) reporter cells to visualize aggregate formation. PBP, showed a direct stimulation of aggregate formation and properties as a NLRP3 inflammasome secondary trigger. TBBPA showed indications of possible secondary triggering activity while no changes were seen with TPP. Thus, the data suggests an effect of all three FRs on mitochondria metabolism yet, different functional outcomes including, phagocytic capability and NLRP3 inflammasome activation.


Assuntos
Organofosfatos/toxicidade , Fenóis/toxicidade , Bifenil Polibromatos/toxicidade , Animais , Retardadores de Chama , Humanos , Camundongos , Microglia , Mitocôndrias/efeitos dos fármacos , Testes de Toxicidade
4.
Artigo em Inglês | MEDLINE | ID: mdl-32466414

RESUMO

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant, which is widely present in the various environmental and biological media. The knowledge on the contamination of TBBPA in Weihe River Basin is still limited. In order to know the pollution level and distribution of tetrabromobisphenol A (TBBPA) in the Weihe River Basin, a total of 34 sediment samples and 36 water samples were collected from the main stream and tributaries of the WeiHe River Basin, and the concentration of TBBPA in the samples was analyzed by high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). The detection frequency of TBBPA in sediments and water samples was 61.8% and 27.8%, respectively; the TBBPA concentrations in sediments and water samples were in the range of not detected (N.D.)-3.889 ng/g (mean value of 0.283 ng/g) and N.D-12.279 ng/L (mean value of 0.937 ng/L), respectively. Compared with other areas in China, the residues of TBBPA in the Weihe River Basin were at a relatively low level. The spatial distributions of TBBPA in surface sediments and water indicated that the local point-input was their major source. This is related to the proximity of some sampling sites to industrial areas and domestic sewage discharge areas. The insignificant correlation between TBBPA and total organic carbon (TOC) indicated that TBBPA in sediments is not only influenced by TOC but also affected by atmosphere and land input, wet deposition, and long-distance transmission. The potential risks posed by TBBPA in water and sediment were characterized using the risk quotient (RQ) method. The calculated RQ for TBBPA was less than 0.01, showing that the ecological risk due to TBBPA was quite low for aquatic organisms.


Assuntos
Bifenil Polibromatos , Rios , Poluentes Químicos da Água , Animais , Organismos Aquáticos , China , Monitoramento Ambiental , Sedimentos Geológicos , Bifenil Polibromatos/análise , Bifenil Polibromatos/toxicidade , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
5.
Ecotoxicol Environ Saf ; 200: 110770, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32450437

RESUMO

Tetrabromobisphenol A (TBBPA) in water from Xiongan New Area was determined by gas chromatography-mass spectrometry (GC-MS), simultaneous with its risk assessment. The optimal extraction conditions, derivatization factors (such as derivation reagent amount, derivatization time and temperature), and dissolution solvent were determined by orthogonal experiment. These results indicated the optimum derivatization time and temperature were 70 °C and 30 min, respectively, whilst the amount of derivatization reagent (N,O-bis (trimethylsilyl) trifluoroacetamide) was 40 µL. The optimum extraction efficiency was obtained when using the mixture of hexane-dichloromethane (1:1, v:v) with salt concentration of 6 g/L. Using the sample of S9 as control, the recovery experiments were performed with three different spiked levels. The water samples of Baiyang Lake and Fuhe river were analyzed using the optimized conditions. Those results showed that the concentrations of TBBPA in samples ranged from 18.5 ng/L to 82.6 ng/L, which lies in the middle level of data previously published from other areas in China. The risk quotient (RQ) model was used to evaluate the above data. The results of exposure and risk assessment showed that the margin of exposure (MOE) was 1.28 × 107-2.5 × 107 and the RQmax was 0.0266. The European Food Safety Authority (EFSA) standard and categories of RQ indicates that the estimated dietary exposure to TBBPA is unlikely to raise significant health concerns. This is the first report on the occurrence and risk assessment of TBBPA in waters from Xiongan New Area, which will be helpful for further risk assessment of other persistent organic pollutants. At present, the toxicological data of TBBPA in the biological body of Baiyang Lake is limited. In addition, more accurate and convenient approaches for the risk assessment of TBBPA should be explored.


Assuntos
Exposição Dietética/análise , Lagos/química , Bifenil Polibromatos/toxicidade , Rios/química , Poluentes Químicos da Água/toxicidade , China , Exposição Dietética/efeitos adversos , Cromatografia Gasosa-Espectrometria de Massas , Bifenil Polibromatos/análise , Medição de Risco , Poluentes Químicos da Água/análise
6.
Chemosphere ; 252: 126422, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32199162

RESUMO

Prenatal exposure to bisphenol A (BPA) and its analogues can affect fetal growth and development. However, epidemiologic findings were inconsistent and there was a lack of study for BPA analogues. We aimed to examine the associations between prenatal exposure to BPA, bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) and birth size. 2023 mother-infant pairs were included in this study. The associations between serum bisphenol levels and birth size were analyzed by multivariate linear regression models. After adjusting for covariates, one log10-unit increase in serum BPA was correlated with a 32.10 g (95% CI: -61.10, -3.10) decrease in birth weight for all infants, and the inverse association was only observed in males when stratified analysis by gender. Additionally, higher BPF concentrations were associated with decreasing birth weight (P for trend = 0.031), ponderal index (P for trend = 0.021), and birth weight Z-scores (P for trend = 0.039) in all infants, and the inverse associations were also only observed in males when stratified analysis by gender. Similarly, higher TBBPA levels were also correlated with decreased birth weight (P for trend = 0.023). However, after gender stratification, higher TBBPA concentrations were associated with a decrease in birth weight (P for trend = 0.007), birth length (P for trend = 0.026), and birth weight Z-scores (P for trend = 0.039) in males. Our data suggested an inverse association of prenatal exposure to BPA, BPF, and TBBPA and birth size, which may be more pronounced in male infants.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Poluentes Ambientais/metabolismo , Exposição Materna/estatística & dados numéricos , Fenóis/metabolismo , Compostos Benzidrílicos/metabolismo , Compostos Benzidrílicos/toxicidade , China/etnologia , Grupos Étnicos , Feminino , Desenvolvimento Fetal , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Fenóis/toxicidade , Bifenil Polibromatos/metabolismo , Bifenil Polibromatos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etnologia , Sulfonas/metabolismo , Sulfonas/toxicidade
7.
Ecotoxicol Environ Saf ; 192: 110255, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32018154

RESUMO

Tetrabromobisphenol A (TBBPA) and its derivatives are the common flame-retardants that may increase the risk of development of many types of cancers, including liver cancer. However, the effects of TBBPA in the development and progression of liver cancer remains unknown. This study investigated the potential effects of TBBPA on a metastatic phenotype of hepatocellular carcinoma cell line-HepG2. Our results revealed that TBBPA significantly promoted the migration and invasion via affecting the number and distribution of lysosomes in HepG2 cells in a dose-dependent manner. Moreover, TBBPA decreased the intracellular protein levels of Beta-Hexosaminidase (HEXB), Cathepsin B (CTSB) and Cathepsin D (CTSD) while increased the extracellular CTSB and CTSD. It entailed that TBBPA exposure could promote the lysosomal exocytosis in cancer cells. The reversal results were obtained after adding lysosomal exocytosis inhibitor vacuolin-1. Docking results suggested that TBBPA could bind to TRPML1. It was consistent with the binding position of agonist ML-SA1. TRPML1 knockdown significantly decreased the invasion and migration, and the results were reversed when TBBPA was added. The results were indicated that TRPML1 was critical in lysosomal exocytosis. In addition, our results showed that TBBPA-TRPML1 complex regulated the calcium-mediated lysosomal exocytosis, thereby promoting the metastasis in liver cancer cells. It was expected that our data could provide important basis for understanding the molecular mechanism(s) of TBBPA promoting invasion and migration of hepatoma cells and give rise to profound concerns of TBBPA exposure on human health.


Assuntos
Carcinoma Hepatocelular/patologia , Exocitose/efeitos dos fármacos , Retardadores de Chama/toxicidade , Neoplasias Hepáticas/patologia , Lisossomos/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Cálcio/metabolismo , Carcinoma Hepatocelular/metabolismo , Movimento Celular/efeitos dos fármacos , Células Hep G2 , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Neoplasias Hepáticas/metabolismo , Invasividade Neoplásica , Canais de Receptores Transientes de Potencial/fisiologia
8.
Chemosphere ; 248: 126067, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32041069

RESUMO

Microplastics (MPs) pollution and its potential environmental risks have drawn increasing concerns in recent years. Among which, microbeads in personal care and cosmetic products has becoming an emerging issue for their abundance as well as the knowledge gaps in their precise environmental behaviors in freshwater. The present study investigated the sorption process of tetrabromobisphenol A (TBBPA), the most widely applied and frequently encountered flame retardant in aquatic environments, on two sources of polyethylene (PE) particles (pristine PE particles and microbeads isolated from personal care and cosmetic products). Significantly enhanced adsorption capacity of microbeads was observed with up to 5-folds higher than the pristine PE particles. The sorption efficiency was also governed by solution pH, especially for the cosmetic-derived microbeads, indicating the strong adsorption of TBBPA on PE was dominated by both hydrophobic and electrostatic interactions. Additionally, combined effects on redox status of zebrafish were evaluated with two environmental relevant concentrations of PE particles (0.5 and 5 mg L-1) using integrated biomarker response (IBR) index through a 14-d exposure. Co-exposure induced significant antioxidative stress than either PE or TBBPA alone when exposed to 0.5 mg L-1 of MPs. After 7-d depuration, the IBR value for combination treatments [TBBPA + PE (L)] was 3-fold compared with that in MP-free groups, indicating the coexistence might exert a prolonged adverse effects on aquatic organisms. These results highlight the probability of risk from microbead pollution in freshwater, where toxic compounds can be adsorbed on microbeads in a considerable amount resulting in potential adverse effects towards aquatic organisms.


Assuntos
Cosméticos/química , Microplásticos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Polietileno/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Adsorção , Animais , Antioxidantes/metabolismo , Organismos Aquáticos/efeitos dos fármacos , Organismos Aquáticos/metabolismo , Sinergismo Farmacológico , Biomarcadores Ambientais/efeitos dos fármacos , Retardadores de Chama/análise , Retardadores de Chama/toxicidade , Água Doce/química , Microplásticos/análise , Microesferas , Bifenil Polibromatos/análise , Polietileno/análise , Poluentes Químicos da Água/análise
9.
Arch Microbiol ; 202(4): 895-903, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31897538

RESUMO

This study investigated the regulatory role of Rhodopseudomonas palustris RP11 in alleviating TBBPA-induced harmful effects in soybean seedlings. In this study, the characteristics of growth promotion by strain RP11 were studied by analysing 5-aminolevulinic acid (ALA) and indole-3-acetic acid (IAA) production, as well as phosphorus-solubilizing and potassium-solubilizing ability. In the pot culture conditions, we tested whether strain RP11 improved soybean seedlings tolerance against TBBPA by measuring the root length and physiological parameters of the seedlings treated with strain RP11 and different concentration of TBBPA (0, 5, 50, 100, and 1000 mg/kg) together. The results showed that strain RP11 secreted IAA and ALA, and solubilized phosphate and potassium. In pot trials, strain RP11 increased the root length, chlorophyll content, carotenoid content, soluble sugar and protein content of soybean seedlings treated with TBBPA, in comparison with the seedlings treated only with TBBPA. Furthermore, strain RP11 induced the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), decreased the malondialdehyde (MDA) content in soybean seedlings under TBBPA stress. It was concluded that strain RP11 alleviated TBBPA-induced harmful effects in soybean seedlings by the secretion of IAA and ALA, the accumulation of carotenoid, soluble sugar and soluble protein, and the induction of SOD, CAT and POD as well as nutrient adjustment of phosphorus and potassium levels.


Assuntos
Bifenil Polibromatos/metabolismo , Rodopseudomonas/metabolismo , Plântula/microbiologia , Soja/microbiologia , Catalase/metabolismo , Clorofila/metabolismo , Ácidos Indolacéticos/metabolismo , Malondialdeído/metabolismo , Peroxidase/metabolismo , Peroxidases/metabolismo , Bifenil Polibromatos/toxicidade , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Soja/efeitos dos fármacos , Soja/crescimento & desenvolvimento , Superóxido Dismutase/metabolismo
10.
Am J Epidemiol ; 189(2): 120-132, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31742588

RESUMO

A nested case-control study was carried out using data from the US Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 histologically confirmed PTC cases (in 341 women and 401 men) and 742 matched controls with prediagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of 8 congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by sex. BDE-28, a polybrominated diphenyl ether congener, was associated with significantly increased risk of classical PTC (for the third tertile vs. below the limit of detection, odds ratio = 2.09, 95% confidence interval: 1.05, 4.15; P for trend = 0.02), adjusting for other congeners, body mass index, and branch of military service. This association was observed mainly for larger classical PTC (tumor size > 10 mm), with a significantly stronger association among women than men (P for interaction = 0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by sex and tumor size.


Assuntos
Poluentes Ambientais/sangue , Éteres Difenil Halogenados/sangue , Bifenil Polibromatos/sangue , Câncer Papilífero da Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/induzido quimicamente , Adulto , Estudos de Casos e Controles , Poluentes Ambientais/toxicidade , Feminino , Éteres Difenil Halogenados/toxicidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Bifenil Polibromatos/toxicidade , Adulto Jovem
11.
Chemosphere ; 242: 125078, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31704520

RESUMO

The widespread use of tetrabromobisphenol A (TBBPA) in industries has resulted in its frequent detection in environmental matrices, and the mechanisms of its associated hazards need further investigation. In this study, the nematode Caenorhabditis elegans (C. elegans) was exposed to environmentally relevant concentrations of TBBPA (0, 0.1, 1, 10, 100, 200 µg/L) to determine its effects. At TBBPA concentrations above 1 µg/L, the number of head thrashes, as the most sensitive physiological indicator, decreased significantly. Using the Illumina HiSeq™ 2000 sequencer, differentially expressed genes (DEGs) were determined, and 52 were down regulated and 105 were up regulated in the 200 µg/L TBBPA treatment group versus the control group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database analysis demonstrated that dorso-ventral axis formation is related to neurotoxicity; metabolism of xenobiotics by Cytochrome P450 (CYP450) and glutathione-S-transferase (GST) was found to be the vital metabolic mechanisms and were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). GST was ascribed to the augmentation because mutations in cyp-13A7 were constrained under TBBPA exposure. Additionally, oxidative stress indicators accumulated in a dose-dependent relationship. These results will help understand the molecular basis for TBBPA-induced toxicity in C. elegans and open novel avenues for facilitating the exploration of more efficient strategies against TBBPA toxicity.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Bifenil Polibromatos/toxicidade , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Perfilação da Expressão Gênica , Glutationa Transferase/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Estresse Oxidativo , Reação em Cadeia da Polimerase em Tempo Real
12.
Chemosphere ; 238: 124602, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545211

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been known to exhibit neurotoxicity in rats; however, the underlying mechanism remains unknown and there is no available intervention. In this study, we aimed to investigate the role of oxidative and nitrosative stress in the neurotoxicity in the cerebral cortex and primary neurons in rats following the BDE-153 treatment. Compared to the untreated group, BDE-153 treatment significantly induced the neurotoxic effects in rats, as manifested by the increased lactate dehydrogenase (LDH) activities and cell apoptosis rates, and the decreased neurotrophic factor contents and cholinergic enzyme activities in rats' cerebral cortices and primary neurons. When compared to the untreated group, the oxidative and nitrosative stress had occurred in the cerebral cortex or primary neurons in rats following the BDE-153 treatment, as manifested by the increments in levels of reactive oxygenspecies (ROS), malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) mRNA and protein expressions, along with the decline in levels of superoxide dismutase (SOD) activity, glutathione (GSH) content, and peroxiredoxin I (Prx I) and Prx II mRNA and protein expressions. In addition, the ROS scavenger N-acetyl-l-cysteine (NAC) or NO scavenger NG-Nitro-l-arginine (L-NNA) significantly rescued the LDH leakage and cell survival, reversed the neurotrophin contents and cholinergic enzymes, mainly via regaining balance between oxidation/nitrosation and antioxidation. Overall, our findings suggested that oxidative and nitrosative stresses are involved in the neurotoxicity induced by BDE-153, and that the antioxidation is a potential targeted intervention.


Assuntos
Córtex Cerebral/patologia , Éteres Difenil Halogenados/toxicidade , Síndromes Neurotóxicas/patologia , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Acetilcisteína/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Glutationa/metabolismo , Éteres Difenil Halogenados/metabolismo , Masculino , Malondialdeído/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Neurotrofina 3/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Estresse Nitrosativo/fisiologia , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
13.
Chemosphere ; 238: 124592, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442778

RESUMO

Tetrabromobisphenol A (TBBPA), a brominated flame retardant used in synthetic polymers and electronics, is present in the aquatic environment and recent evidence suggests it can be potentially biomagnified in the marine ecosystem. However, the toxicity of TBBPA in the marine biota has not been investigated in detail. In this study we aimed to understand the role of carboxylesterases (CEs) in xenobiotic metabolism under the exposure of marine organisms to a chemical of environmental concern, TBBPA. Specifically, we tested for in vitro inhibition of CE activity in a range of marine organisms covering different ecological niches, from species from low (mussels and copepods), medium (sardines and anchovies) and high trophic levels (tuna). The results revealed that the highest inhibition of CE activity to 100 µM TBBPA was recorded in mussels (66.5% inhibition) and tunids (36.3-76.4%), whereas copepods and small pelagic fish showed comparatively lower effects (respectively, 30% and 36.5-55.6%). Our results suggest that CE-mediated detoxification and physiological processes could be compromised in TBBPA-exposed organisms and could ultimately affect humans as many of them are market species.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ecossistema , Peixes/metabolismo , Halogenação , Humanos , Alimentos Marinhos
14.
Sci Total Environ ; 697: 134040, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31476509

RESUMO

Polybrominated biphenyls (PBBs) were widely used as additive brominated flame retardants. Their hydroxylated products (OH-PBBs) have been detected frequently in various marine mammals, causing an increased health risk. Till now, there lacks information on the potential disruption of OH-PBBs toward thyroid hormone receptor (TR) and the molecular characteristics of their interactions remain largely unknown. We herein in vitro and in silico evaluated the disrupting effect of 3,3',5,5'-tetrabromobiphenyl (BB80) and its metabolite 2,2'-dihydroxy- 3,3',5,5'-tetrabromobiphenyl (OH-BB80) toward human TR. The recombinant human TRß two-hybrid yeast assay reveals the moderate antagonistic activity of OH-BB80 with IC20 at 2 µmol/L, while BB80 shows no agonistic or antagonistic activity. OH-BB80 binds at the binding cavity of TRß ligand binding domain (LBD) and forms one hydrogen bond with Phe272. Electrostatic interactions and hydrophobic interactions contribute much to their interactions. The binding of OH-BB80 quenches the intrinsic fluorescence of TRß LBD at static quenching mode. Our study extends knowledge on the endocrine disrupting effect of OH-PBBs and suggests the full consideration of the biotransformation for further health risk assessment of PBBs and related structurally similar emerging contaminants.


Assuntos
Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Receptores dos Hormônios Tireóideos/metabolismo , Disruptores Endócrinos/toxicidade , Humanos , Receptores dos Hormônios Tireóideos/antagonistas & inibidores , Glândula Tireoide
15.
Neurotoxicology ; 75: 136-147, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31541695

RESUMO

Tetrabromobisphenol A (TBBPA) has become a ubiquitous indoor contaminant due to its widespread use as an additive flame retardant in consumer products. Reported evidence of endocrine disruption and accumulation of TBBPA in brain tissue has raised concerns regarding its potential effects on neurodevelopment and behavior. The goal of the present study was to examine the impact of developmental TBBPA exposure, across a wide range of doses, on sexually dimorphic non-reproductive behaviors in male and female Wistar rats. We first ran a pilot study using a single TBBPA dose hypothesized to produce behavioral effects. Wistar rat dams were orally exposed using cookie treats to 0 or 0.1 mg TBBPA/kg bw daily from gestational day (GD) 9 to postnatal day (PND) 21 to assess offspring (both sexes) activity and anxiety-related behaviors. Significant effects were evident in females, with exposure increasing activity levels. Thus, this dose was used as the lowest TBBPA dose in a subsequent, larger study conducted as part of a comprehensive assessment of TBBPA toxicity. Animals were exposed to 0, 0.1, 25, or 250 mg TBBPA/kg bw daily by oral gavage starting on GD 6 through PND 90 (dosed dams GD 6 - PND 21, dosed offspring PND 22 - PND 90). Significant behavioral findings were observed for male offspring, with increased anxiety-like behavior as the primary phenotype. These findings demonstrate that exposure to environmental contaminants, like TBBPA, can have sex-specific effects on behavior highlighting the vulnerability of the developing brain.


Assuntos
Comportamento Animal/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Animais , Relação Dose-Resposta a Droga , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar/crescimento & desenvolvimento , Fatores Sexuais
16.
Chemosphere ; 236: 124413, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545206

RESUMO

TBBPA is one of the main brominated flame retardants and is ubiquitous in the environment. TBBPA can directly encounter immune cells via the bloodstream, posing potential immunotoxicity. To understand the immunomodulating effect of TBBPA on macrophages, the murine macrophages, RAW 264.7, were exposed to TBBPA at environmentally relevant concentrations (1-100 nM). The results showed that TBBPA at the selected concentrations did not alter cell viability of RAW 264.7 cells with or without LPS stimulation. TBBPA upregulated the expression of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, whereas it attenuated the LPS-stimulated expression of these pro-inflammatory cytokines, and the expression of anti-inflammatory cytokines, including IL-4, IL-10, and IL-13. In addition, TBBPA reduced the mRNA levels of antigen-presenting-related genes, including H2-K2, H2-Aa, Cd80, and Cd86. Moreover, TBBPA impaired the phagocytic activity of macrophages. Furthermore, exposure to TBBPA significantly elevated the protein levels of phosphorylated NF-κB p65 (p-p65), while it reduced LPS-stimulated p-p65 protein levels. DCFH-DA staining assays showed that TBBPA caused a slight but significant elevation in reactive oxygen species levels. The data obtained in the present study demonstrated that exposure to environmentally relevant concentrations of TBBPA posed immunotoxicity in macrophages and unveiled a potential health risk of TBBPA.


Assuntos
Poluentes Ambientais/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Bifenil Polibromatos/toxicidade , Animais , Antígeno B7-2/genética , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Retardadores de Chama/toxicidade , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Chemosphere ; 235: 701-712, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31279120

RESUMO

This study systematically investigated the performance of ozonation on tetrabromobisphenol A (TBBPA) degradation under different ozone dosages (5.21-83.33 µmoL/L), initial solution pH (3.0-11.0) and temperatures (10-50 °C). At the same time, the generations of inorganic products (bromide ion and bromate) under different experimental conditions were evaluated and the organic products were also identified. Then, the possible mechanism was proposed and verified by the quantum chemical calculation. In addition, variations and controlling of the toxicity were also analyzed, including acute toxicity, chronic toxicity and genotoxicity. Ozonation was proved to be an efficient and promising technology for removing TBBPA from water. TBBPA of 1.84 µmoL/L could be completely degraded within 5 min under the ozone dosage of 41.67 µmoL/L in wide ranges of pH (3.0-11.0) and temperature (10-40 °C). During the degradation of TBBPA, over 65% of the average bromine ion was detected and nine products were identified. The proposed degradation pathways verified that TBBPA might undergo addition and stepwise oxidative debromination, the hydrogen extraction, and the deprotonation. The results of toxicity testing showed that ozonation could effectively control the acute and chronic toxicity of the water samples, although the toxicity increased in the initial reaction stage due to the accumulation of more toxic intermediates.


Assuntos
Ozônio/química , Bifenil Polibromatos/química , Poluentes Químicos da Água/química , Bromatos , Oxirredução , Bifenil Polibromatos/toxicidade , Testes de Toxicidade , Água , Poluentes Químicos da Água/toxicidade
18.
Environ Pollut ; 253: 909-917, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351299

RESUMO

Tetrabromobisphenol A (TBBPA) is a nonregulated brominated flame retardant with a high production volume, and it is applied in a wide variety of consumer products. TBBPA is ubiquitous in abiotic matrices, wildlife and humans around the world. This paper critically reviews the published scientific data concerning the disposition, metabolism or kinetics and toxicity of TBBPA in animals and humans. TBBPA is rapidly absorbed and widely distributed among tissues, and is excreted primarily in the feces. In rats, TBBPA and its metabolites have limited systemic bioavailability. TBBPA has been detected in human milk in the general population. It is available to both the developing fetus and the nursing pups following maternal exposure. It has been suggested that TBBPA causes acute toxicity, endocrine disruptor activity, immunotoxicity, neurotoxicity, nephrotoxicity, and hepatotoxicity in animals. Cell-based assays have shown that TBBPA can induce reactive oxygen species in a concentration-dependent manner, and it promotes the production of inflammatory factors such as TNF α, IL-6, and IL-8. Cells exposed to high levels of TBBPA exhibit seriously injured mitochondria and a dilated smooth endoplasmic reticulum. This review will enhance the understanding of the potential risks of TBBPA exposure to ecological and human health.


Assuntos
Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Animais , Animais Selvagens , Disponibilidade Biológica , Fezes , Feminino , Retardadores de Chama/metabolismo , Halogenação , Humanos , Cinética , Masculino , Exposição Materna , Ratos
19.
Chemosphere ; 227: 93-99, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30986606

RESUMO

Currently, more and more concerns are related to oxidative stress appearing in cells as a result of xenobiotics action. It has been found that selected brominated flame retardants (BFRs) can cause reactive oxygen species (ROS) induction at environmental concentrations. Excessive ROS induction can contribute to the redox imbalance in the cell. Therefore, the aim of our work was to evaluate the effect of selected BFRs on the activity of antioxidant enzymes, i.e. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the level of reduced glutathione (GSH) in human erythrocytes. Erythrocytes were incubated with tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) in the concentration ranging from 1 to 100 µg/ml. This study has shown that the BFRs studied disturbed redox balance in human erythrocytes. TBBPA caused more significant decrease in antioxidant enzymes activities than other compounds examined. Among bromophenols studied, 2,4-DBP most strongly affected antioxidant system, which indicated that the number of bromine atoms in the molecule did not significantly affect the pro-oxidative properties of the BFRs examined.


Assuntos
Antioxidantes/metabolismo , Retardadores de Chama/toxicidade , Bromo , Catalase/metabolismo , Eritrócitos/efeitos dos fármacos , Retardadores de Chama/análise , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Halogenação , Humanos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fenóis , Bifenil Polibromatos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
20.
Ecotoxicol Environ Saf ; 179: 104-110, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31026748

RESUMO

Tetrabromobisphenol A bis(2,3-dibromopropyl) ether (TBBPA-BDBPE) is an additive flame retardant used in polyolefins and polymers. It has been detected in biota, including in avian eggs, yet little is known of its effects. We assessed the pattern of TBBPA-BDBPE concentrations in songbird eggs over the incubation period, and the effects of embryonic exposure to TBBPA-BDBPE in a model songbird species, the zebra finch (Taeniopygia guttata). To assess concentrations during embryo development, eggs were injected on the day they were laid with the vehicle control (safflower oil) or 100 ng TBBPA-BDBPE/g egg, and whole egg contents were collected throughout embryonic development on day 0 (unincubated), 5, 10 and 13. To evaluate effects of embryonic exposure to TBBPA-BDBPE, eggs were injected at Hamburger-Hamilton stage 18 (∼80 h after initiation of incubation) with safflower oil only, 10, 50 or 100 ng TBBPA-BDBPE/g egg (albumin injection volume 1 µl/g). Eggs were monitored for hatching success, and nestlings were monitored for growth and survival. At 15 days post-hatch, tissues were collected to assess physiological effects. TBBPA-BDBPE was incorporated into the egg as the embryo developed, and concentrations started declining in late incubation, suggesting biotransformation by the embryo. There were no effects on hatching success, nestling survival, growth, organ somatic indices, or thyroid hormone homeostasis; however, there was evidence that body condition declined in a dose-dependent manner towards the end of the rapid nestling growth phase. This decreased body condition could be a delayed effect of early developmental exposure, or it may be the result of increased exposure to biotransformation products of TBBPA-BDBPE produced over the nestling period, which are predicted to be more bioaccumulative and toxic than the parent compound.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Tentilhões/crescimento & desenvolvimento , Retardadores de Chama/toxicidade , Óvulo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Animais , Tentilhões/metabolismo , Óvulo/metabolismo
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