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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Ecotoxicol Environ Saf ; 179: 151-159, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31035249

RESUMO

Tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTPBE) are both brominated flame retardants (BFRs) that have been detected in birds; however, their potential biological effects are largely unknown. We assessed the effects of embryonic exposure to TBBPA-BDBPE and BTBPE in a model avian predator, the American kestrel (Falco sparverius). Fertile eggs from a captive population of kestrels were injected on embryonic day 5 (ED5) with a vehicle control or one of three doses within the range of concentrations that have been detected in biota (nominal concentrations of 0, 10, 50 or 100 ng/g egg; measured concentrations 0, 3.0, 13.7 or 33.5 ng TBBPA-BDBPE/g egg and 0, 5.3, 26.8 or 58.1 ng BTBPE/g egg). Eggs were artificially incubated until hatching (ED28), at which point blood and tissues were collected to measure morphological and physiological endpoints, including organ somatic indices, circulating and glandular thyroid hormone concentrations, thyroid gland histology, hepatic deiodinase activity, and markers of oxidative stress. Neither compound had any effects on embryo survival through 90% of the incubation period or on hatching success, body mass, organ size, or oxidative stress of hatchlings. There was evidence of sex-specific effects in the thyroid system responses to the BTBPE exposures, with type 2 deiodinase (D2) activity decreasing at higher doses in female, but not in male hatchlings, suggesting that females may be more sensitive to BTBPE. However, there were no effects of TBBPA-BDBPE on the thyroid system in kestrels. For the BTPBE study, a subset of high-dose eggs was collected throughout the incubation period to measure changes in BTBPE concentrations. There was no decrease in BTBPE over the incubation period, suggesting that BTBPE is slowly metabolized by kestrel embryos throughout their ∼28-d development. These two compounds, therefore, do not appear to be particularly toxic to embryos of the American kestrel.


Assuntos
Bromobenzenos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Falconiformes/crescimento & desenvolvimento , Retardadores de Chama/toxicidade , Óvulo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Animais , Relação Dose-Resposta a Droga , Desenvolvimento Embrionário/fisiologia , Falconiformes/metabolismo , Feminino , Iodeto Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Óvulo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/metabolismo
8.
Chemosphere ; 226: 463-471, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951941

RESUMO

Tetrabromobisphenol A (TBBPA) is a commonly used brominated flame retardant, which has a wide range of toxic effects on organisms. This study investigated the cytotoxic effects on human hepatocytes (L02 cells) after treated with 0, 5, 10, 20, and 40 µM of TBBPA. Results showed that TBBPA significantly increased intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and the ratio of oxidized/reduced glutathione (GSSG/GSH) dose-dependently. TBBPA also decreased the cell mitochondrial membrane potential (MMP), caused the release of cytochrome C (Cyt C) to cytoplasm and promoted the expression of caspase-9 and caspase-3, and finally increased the level of apoptosis. The ROS inhibitor N-acetyl-L-cysteine (NAC) relieved the oxidative stress responses, and prevented the decrease of MMP and increase of apoptosis. In addition, TBBPA promoted the expression of antioxidant genes related to Nrf2, such as quinone oxidoreductase 1 (NQO1), catalase (CAT), and heme oxygenase 1 (HO-1). Oxidative stress initiated by TBBPA, activated mitochondrial apoptosis and Nrf2 pathway, and increased the degree of apoptosis in L02 cells.


Assuntos
Apoptose/efeitos dos fármacos , Retardadores de Chama/toxicidade , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Acetilcisteína/farmacologia , Caspase 3/biossíntese , Caspase 9/biossíntese , Catalase/metabolismo , Linhagem Celular , Citocromos c/metabolismo , Glutationa/metabolismo , Heme Oxigenase-1/biossíntese , Heme Oxigenase-1/genética , Hepatócitos/efeitos dos fármacos , Humanos , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
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
10.
Toxicol Lett ; 311: 37-48, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31029751

RESUMO

Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons, however, the roles of mitochondria and endoplasmic reticulum (ER) remain unclear in the BDE-153-induced neuronal apoptosis. To this purpose, we observed the mitochondria and ER ultrastructure changes in the neuronal apoptosis in rats following BDE-153 treatment, detected the mitochondrial membrane potential (MMP), Ca2+-Mg2+-ATP enzyme activity, and the changes of mitochondria and ER apoptosis related molecules in rat cerebral cortex and in primary neurons following BDE-153 treatment. Results showed that compared to the control group, neuronal apoptosis was significantly increased in a dose-dependent manner in rat cerebral cortex and in primary neurons following BDE-153 treatment. In comparison with control, BDE-153 treatment induced remarkable ultrastructural changes in ER rather than in mitochondria, and the severity of ER damage was worse with the increasing BDE-153 dose. Meanwhile, ER apoptosis related molecules including caspase-12 (at mRNA level), cleaved caspase-12 (at protein level), and Tmem132a (at mRNA and protein levels) were significantly increased in the cerebral cortex in rats following BDE-153 treatment, while procaspase-12 protein was significantly decreased, comparing with control. In contrast, mitochondria apoptosis related molecules (MMP, Ca2+-Mg2+-ATP enzyme activity, cyt-C protein, caspase-3, 8, 9 mRNA, caspase-8, 9 enzyme activities) did not significantly changed in the cerebral cortex of rats or in primary neurons following BDE-153 treatment, except for the elevated caspase-3 mRNA and enzyme activity. Therefore, we conclude that BDE-153 induced neuronal apoptosis was dependent on p53, and mediated more by ER than mitochondria in the cerebral cortex of rats and in primary neurons. The findings suggest that ER is a potential sensitive target of BDE-153 neurotoxicity, providing a scientific evidence for the mechanism and intervention study on PBDE's neurotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Degeneração Neural , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Bifenil Polibromatos/toxicidade , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/ultraestrutura , Relação Dose-Resposta a Droga , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/ultraestrutura , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Neurônios/metabolismo , Neurônios/ultraestrutura , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
11.
Int J Mol Sci ; 20(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934780

RESUMO

The effects of thyroid hormone disrupting chemicals (THDCs) on eye development of zebrafish were investigated. We expected THDC exposure to cause transcriptional changes of vision-related genes, which find their phenotypic anchoring in eye malformations and dysfunction, as observed in our previous studies. Zebrafish were exposed from 0 to 5 days post fertilization (dpf) to either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or tetrabromobisphenol-A (TBBPA), which interacts with thyroid hormone receptors. Full genome microarray analyses of RNA isolated from eye tissue revealed that the number of affected transcripts was substantially higher in PTU- than in TBBPA-treated larvae. However, multiple components of phototransduction (e.g., phosphodiesterase, opsins) were responsive to both THDC exposures. Yet, the response pattern for the gene ontology (GO)-class "sensory perception" differed between treatments, with over 90% down-regulation in PTU-exposed fish, compared to over 80% up-regulation in TBBPA-exposed fish. Additionally, the reversibility of effects after recovery in clean water for three days was investigated. Transcriptional patterns in the eyes were still altered and partly overlapped between 5 and 8 dpf, showing that no full recovery occurred within the time period investigated. However, pathways involved in repair mechanisms were significantly upregulated, which indicates activation of regeneration processes.


Assuntos
Disruptores Endócrinos/toxicidade , Olho/embriologia , Hormônios Tireóideos/toxicidade , Peixe-Zebra/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Olho/efeitos dos fármacos , Perfilação da Expressão Gênica , Bifenil Polibromatos/toxicidade , Propiltiouracila/toxicidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Genética/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
12.
Ecotoxicol Environ Saf ; 174: 408-416, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851538

RESUMO

Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants, have been extensively applied and eventually leached into the surrounding environment. Marine microalgae are not only the dominant primary producers of marine ecosystem, but also food source for aquaculture. PBDEs have been found to remarkably inhibit growth, photosynthesis and metabolism of marine microalgae. However, whether they also affect swimming behavior of marine motile microalgae remains unknown. We chose BDE-47, BDE-99 and BDE-153 as model PBDEs, and the unicellular marine green flagellate, Platymonas subcordiformis, as test organism to figure out this issue. After two-hour exposure, motile cells proportion (MOT), swimming velocity (VCL, VAP and VSL), and swimming pattern (LIN and STR) of P. subcordiformis were measured via computer assisted cell movement tracking. Results suggest that the three PBDEs not only reduced motile cells proportion and swimming velocity, but also altered swimming pattern. BDE-47 was more toxic than BDE-99, followed by BDE-153, indicating their toxicity decreased as bromination degree increases. Swimming ability of P. subcordiformis was even completely arrested when BDE-47 and BDE-99 at 32 µg/L. The impairment of swimming ability by PBDEs might thereby hinder growth and survival of marine microalgae, and subsequently threaten marine ecosystem and aquaculture industry. More importantly, this study implies that marine microalgae swimming behavior test is more efficiency and sensitive than traditional marine microalgal bioassays, like growth and photosynthesis tests. We suggest that although future work is needed, swimming behavior analysis of P. subcordiformis with MOT, VCL and VAP as endpoints can be developed as a low-cost, convenient, fast, reliable and sensitive method for seawater quality assessment.


Assuntos
Éteres Difenil Halogenados/toxicidade , Microalgas/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Água do Mar/química , Natação , Poluentes Químicos da Água/toxicidade , Animais , Ecossistema , Microalgas/fisiologia , Modelos Teóricos
13.
Environ Sci Pollut Res Int ; 26(13): 12788-12797, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887452

RESUMO

In this study, health risk of human exposure to organohalogenated pollutants (OHPs) through milk consumption was determined. Conventionally produced, unprocessed cow's milk samples taken from Konya District, in Turkey, and 15 different brand ultra-high-temperature (UHT) processed cow's milk samples taken from supermarkets of Turkey were analyzed for organochlorine pesticides (OCPs, α-, ß-, γ-, and δ-HCHs, p,p'-DDE, p,p'-DDD, and p,p'-DDT, heptachlor, heptachlor epoxide, endosulfan I, endosulfan II, endosulfan sulfate, endrin, endrin aldehyde, endrin ketone, aldrin + dieldrin, methoxychlor), polychlorinated biphenyls (PCBs, PCB 28, 52, 101, 153, 138, and 180), and polybrominated diphenyl ethers (PBDEs, PBDE 47, 99, 100, 153, and 154 congeners). Estimated daily intake (EDI) values calculated for both adults and children consuming raw or UHT milk were determined to exceed maximum residue limits (MRLs) set for γ-HCH, ∑Heptachlor, and endrin. EDI values also exceeded admissible daily intake (ADI) values given for ∑HCH, ∑Heptachlor, ∑Endrin aldrin + dieldrin, and ∑PCBs. p,p'-DDT/p,p'-DDE ratio was 1 or higher for 66% of the milk samples, which is an indication of sustaining illegal use of DDT. A health risk is determined for dietary intake of OHPs via consumption of milk.


Assuntos
Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Hidrocarbonetos Clorados/análise , Leite/química , Adulto , Animais , Bovinos , Criança , Exposição Dietética/efeitos adversos , Poluentes Ambientais/toxicidade , Feminino , Humanos , Hidrocarbonetos Clorados/toxicidade , Pasteurização/métodos , Praguicidas/análise , Praguicidas/toxicidade , Bifenil Polibromatos/análise , Bifenil Polibromatos/toxicidade , Medição de Risco , Temperatura Ambiente , Turquia
14.
Environ Toxicol ; 34(6): 742-752, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30835936

RESUMO

Brominated flame retardants (BFRs) are supposed to act as disruptors of cell signaling, but the underlying mechanisms remain less clear. Human bronchial epithelial cells (BEAS-2B) were used to investigate the toxic effect and gene expression changes induced by tetrabromobisphenol A (TBBPA). By genome-wide approaches with Illumina RNA-seq, 87 genes were identified to exhibit ≥1.5-fold changes in expression after treatment by TBBPA for 48 h, among which, 79 were upregulated and 8 were downregulated. Gene ontology (GO) annotation enriched unigenes were divided into three clusters: biological process (BP), cellular component (CC) and molecular function (MF). Pathway analysis showed that NF-κB, TNF signaling, toll-like receptor, MAPK signaling and B-cell receptor were the most prominent pathways affected by TBBPA, which play key roles in regulating cell proliferation and cell differentiation, inflammatory response. Finally, for verifying the accuracy of microarray analysis, qRT-PCR was used to analyze the transcription level of key genes in the above signaling pathways, and ELISA assay confirmed the effect of TBBPA on the levels of CXCL-2, CCL-3, CCL-4, IL-1ß, TNF-α, and IL-6. These findings provided important information for further exploitation of the mechanisms under-lying BFR-induced adverse health effects.


Assuntos
Células Epiteliais/efeitos dos fármacos , Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Transcriptoma/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Estudo de Associação Genômica Ampla , Humanos , Transdução de Sinais , Regulação para Cima
15.
Chemosphere ; 224: 588-596, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30844590

RESUMO

Tetrabromobisphenol A (TBBPA) is ubiquitous and its contents showing an increasing trend in the coastal environment. In order to investigate the effects of TBBPA on marine bivalves, juvenile manila clams Ruditapes phillipinarum were exposed to TBBPA for 28 days. The results showed that shell growth rate of juvenile clams after exposure to 62.5-1000 µg L-1 TBBPA for 28 d were significantly inhibited (p < 0.05). Then in order to link the changes in filtration rate, mRNA expression of insulin-like growth factor homologue (IGF) and tissue thyroid hormone (TH) contents to growth, juvenile clams were exposed to 62.5 and 500 µg L-1 TBBPA for 14 days. The transcriptional levels of neuroendocrine signals (NPF and insulin homologue) associated with filter feeding regulation, and genes of TH synthesis-related enzymes were also examined. The results showed that filtration rates was significantly reduced to 44.1% and 14% of controls after 14 d of exposure. In parallel, exposure to TBBPA significantly increased the expression levels of insulin which may elicit the filter feeding inhibition. TBBPA exposure caused alterations in tissue content of THs and mRNA expression of TH synthesis-related enzymes. However, the data showed increased T3 content, T3/T4 ratio and mRNA expression of IGF. These data demonstrated that the most important key event of TBBPA could be linked to growth impairment in juveniles was the reduction of filtration rate. These results provide a robust framework towards revealing the underlying mechanism of the growth inhibition caused by TBBPA on bivalves and understanding the adverse outcome pathway across taxonomic phyla.


Assuntos
Rotas de Resultados Adversos , Bivalves/crescimento & desenvolvimento , Regulação da Expressão Gênica/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bivalves/efeitos dos fármacos , Bivalves/metabolismo , Hormônios Tireóideos/metabolismo
16.
Chemosphere ; 223: 64-73, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30769291

RESUMO

The brominated flame retardant tetrabromobisphenol A (TBBPA) is toxic to cultured brain neurons, and glutamate receptors partially mediate this effect; consequently, the depolarizing effect of TBBPA on neurons is to be expected, but it is yet to be actually demonstrated. The aim of this study was to detect TBBPA-evoked depolarization and identify the underlying mechanisms. The plasma membrane potential of rat cerebellar granule cells (CGC) in cerebellar slices or in primary cultures was measured using whole-cell current clamp recordings, or the fluorescent probe oxonol VI, respectively. The contribution of NMDA and AMPA receptors, voltage-gated sodium channels and intracellular calcium mobilization was tested using their selective antagonists or inhibitors. Direct interactions of TBBPA with NMDARs were tested by measuring the specific binding of radiolabeled NMDAR ligands to isolated rat cortical membrane fraction. TBBPA (25 µM) strongly depolarized CGC in cerebellar slices, and at ≥ 7.5 µM concentration-dependently depolarized primary CGC cultures. Depolarization of the primary CGC by 25 µM TBBPA was partly reduced when MK-801 was applied alone or in combination with either TTX or CNQX, or where bastadin 12 was applied in combination with ryanodine, whereas depolarization was completely prevented when MK-801, CNQX and TTX where combined. TBBPA had no effect on the specific binding of NMDAR radio-ligands to isolated cortical membranes. These results demonstrate the depolarizing effect of TBBPA on CGC, which is mainly mediated by ionotropic glutamate receptors, while voltage-gated sodium channels are also involved. We found no evidence for the direct activation of NMDARs by TBBPA.


Assuntos
Cerebelo/patologia , Potenciais da Membrana/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Animais , Células Cultivadas , Retardadores de Chama/toxicidade , Fármacos Neuromusculares Despolarizantes , Neurônios/patologia , Técnicas de Patch-Clamp , Ratos , Receptores Ionotrópicos de Glutamato/metabolismo , Receptores Ionotrópicos de Glutamato/fisiologia
17.
Aquat Toxicol ; 209: 99-112, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30763833

RESUMO

Brominated flame retardants are known to disrupt thyroid hormone (TH) homeostasis in several vertebrate species, but the molecular mechanisms underlying this process and their effects on TH-sensitive tissues during the stages of early development are not well characterised. In this study, we exposed zebrafish (Danio rerio) embryo-larvae to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and tetrabromobisphenol A (TBBPA) via the water for 96 h from fertilisation and assessed for lethality, effects on development and on the expression of a suite of genes in the hypothalamic-pituitary-thyroid (HPT) axis via both real time quantitative PCR (qRT-PCR) on whole body extracts and whole mount in situ hybridisation (WISH) to identify tissue targets. The 96-h lethal median concentration (96h-LC50) for TBBPA was 0.9 µM and mortality was preceded by retardation of development (smaller animals) and morphological deformities including, oedemas in the pericardial region and tail, small heads, swollen yolk sac extension. Exposure to BDE-47 did not affect zebrafish embryo-larvae survival at any of the concentrations tested (1-100 µM) but caused yolk sac and craniofacial deformities, a curved spine and shorter tail at the highest exposure concentration. TBBPA exposure resulted in higher levels of mRNAs for genes encoding deiodinases (dio1), transport proteins (ttr), the thyroid follicle synthesis protein paired box 8 (pax8) and glucuronidation enzymes (ugt1ab) and lower levels of dio3b mRNAs in whole body extracts, with responses varying with developmental stage. BDE-47 exposure resulted in higher levels of thrb, dio1, dio2, pax8 and ugt1ab mRNAs and lower levels of ttr mRNAs in whole body extracts. TBBPA and BDE-47 therefore appear to disrupt the TH system at multiple levels, increasing TH conjugation and clearance, disrupting thyroid follicle development and altering TH transport. Compensatory responses in TH production/ metabolism by deiodinases were also evident. WISH analyses further revealed that both TBBPA and BDE-47 caused tissue-specific changes in thyroid receptor and deiodinase enzyme expression, with the brain, liver, pronephric ducts and craniofacial tissues appearing particularly responsive to altered TH signalling. Given the important role of TRs in mediating the actions of THs during key developmental processes and deiodinases in the control of peripheral TH levels, these transcriptional alterations may have implications for TH sensitive target genes involved in brain and skeletal development. These findings further highlight the potential vulnerability of the thyroid system to disruption by BFRs during early developmental windows.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Especificidade de Órgãos/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Larva/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Testes de Toxicidade Aguda , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
18.
Epigenetics ; 14(1): 52-66, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30676242

RESUMO

In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBB-associated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways.


Assuntos
Células Sanguíneas/efeitos dos fármacos , Metilação de DNA , Disruptores Endócrinos/toxicidade , Bifenil Polibromatos/toxicidade , Adulto , Idoso , Ilhas de CpG , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sequências Reguladoras de Ácido Nucleico
19.
Regul Toxicol Pharmacol ; 102: 108-114, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30593853

RESUMO

Tetrabromobisphenol A (TBBPA) is a flame retardant used in a variety of products, including epoxy and polycarbonate resins. Relevant exposure to TBBPA has been assessed by measuring TBBPA in the blood of humans. Here, we derive Biomonitoring Equivalents (BEs) for TBBPA to interpret these, and future biomonitoring results for TBBPA in humans. The available toxicity risk values (TRVs) for TBBPA were all based on toxicology studies in rats. Several studies have been conducted in which TBBPA in blood of rats were measured following controlled oral doses of TBBPA. These data provide a robust relationship from which to derive BEs. BEs of 5.6 and 13.0 µg total TBBPA/L plasma were calculated for available cancer and non-cancer TRVs, respectively. Several studies have measured TBBPA in serum, with median concentrations less than 0.1 µg/L, indicating considerable margins of safety (MOS) for TBBPA based on the currently available biomonitoring studies.


Assuntos
Retardadores de Chama/análise , Bifenil Polibromatos/sangue , Animais , Monitoramento Ambiental , Retardadores de Chama/farmacocinética , Retardadores de Chama/toxicidade , Humanos , Bifenil Polibromatos/farmacocinética , Bifenil Polibromatos/toxicidade , Ratos
20.
Toxicol Lett ; 301: 108-113, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30481582

RESUMO

Tetrabromobisphenol A Bis(2,3-dibromopropyl) ether (TBBPA-BDBPE) is a high production volume brominated flame retardant (BFR) used in consumer products, resulting in ubiquitous human exposure. Although the major route of exposure for this chemical is believed to be via ingestion, dermal contact is likely via contaminated dust. Independent trials of a single dose of 100 nmol/cm2 (∼1 µCi [14C]/cm2) of [14C]-radiolabeled TBBPA-BDBPE was applied to whole rat skin (in vivo) or split-thickness human and rat skin (ex vivo) to estimate in vivo human percutaneous uptake. [14C]-radioactivity was quantified to determine dermal absorption (dose retained in dosed skin) and penetrance (dose recovered in receptor fluid [ex vivo] or tissues/excreta [in vivo]) over 24 h. In vivo absorption and penetration for rat skin was 26% and 1%, with a maximum flux of 44 ± 9 pmol/cm2/h. In ex vivo rat skin, absorption and penetration and absorption values were 23% and 0.3% (flux = 26 ± 8 pmol/cm2/h). In ex vivo human skin, 53% was absorbed and penetration was 0.2% with a maximal flux of 16 ± 12 pmol/cm2/h. Computed maximal flux for in vivo human skin was 21 ± 9 pmol/cm2/h with expected total absorption of ∼80% and a penetration of <1%. HPLC-radiometric analyses of samples showed that TBBPA-BDBPE was not metabolized in ex vivo or in vivo studies. These studies indicate that TBBPA-BDBPE is likely to be dermally bioavailable even after washing and dermal contact with this chemical should be considered an important route of exposure.


Assuntos
Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Absorção Cutânea , Pele/efeitos dos fármacos , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Pele/metabolismo
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