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1.
Environ Pollut ; 307: 119564, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35654249

RESUMO

Triphenyl phosphate (TPHP) is a frequently used flame retardant and indoor semi-volatile pollutant exposing humans with endocrinal disrupting effects. However, its respiratory tract toxicity remains unclear. Herein, we mainly focused on exploring the cytotoxicity of TPHP to the cells from five different parts of the human respiratory tract (from top to bottom): human nasal epithelial (HNEpC) cells, human bronchial epithelial (16HBE) cells, normal nasopharyngeal epithelial (NP69) cells, human lung epithelial cells (Beas-2B) cells, and human lung fibrocells (HFL1 cells) cells. The cell viability, micronucleus induction, endoplasmic reticulum stress gene, intracellular Ca2+ concentration, mitochondrial membrane potential (MMP) were investigated in short-term as well as extended exposure of TPHP. HFL1 and HNEpC cells were found to be irreversible damage, while other three type cells achieved homeostasis through self-rescue. Moreover, expression of downstream genes of Nrf2 signaling pathway were upregulated for 1.3-7.0 times and glutathione detoxification enzyme activity changed for 2-10 (U/mg protein) in HNEpC cells. Furthermore, the vascular endothelial growth factor (VEGF), a disease-related factor, increased 1.0-3.5-fold in HNEpC cells. RNA-sequencing results suggested that protein linkage recombination, molecular function regulation and metabolic processes signal pathway were all affected by TPHP exposure in HNEpC. This is a first report to compare respiratory cytotoxicity in whole human respiratory tract under OPFR exposure and found HNEpC cells were the most sensitive target of TPHP. Molecular biological mechanisms uncovered that TPHP exposure in HNEpC can induce the activation of MAPK signal pathway and demonstrate potential respiratory growth differentiation and stress disorder in human nasal cells upon TPHP exposure.


Assuntos
Poluentes Ambientais , Retardadores de Chama , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Humanos , Organofosfatos/metabolismo , Organofosfatos/toxicidade , Compostos Organofosforados/toxicidade , Sistema Respiratório/metabolismo , Fator A de Crescimento do Endotélio Vascular
2.
Curr Microbiol ; 79(7): 200, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35596087

RESUMO

1,2,5,6,9,10-Hexabromocyclododecanes (HBCDs) are brominated flame retardants causing serious environmental pollution. HBCDs in the environment could be transformed to various products. Identification of transformation products has been performed using various mass-spectrometric techniques. However, bacterial transformation of HBCDs yielding low-level products was not well studied. In this paper, a Rhodococcus strain stu-38 which could stereoselectively transform HBCDs in mineral salt medium, seawater, and growth medium was isolated. Seven potential biotransformation products of HBCDs were identified by using GC-MS. These products, including brominated alkenes, dibromocyclododecadiene and bromocyclododecatriene; brominated alkenols, bromocyclododecadienol and bromocyclododecatrienol; fully debrominated compounds, cyclododecadiendiol, 1,2-epoxy-5,9-cyclododecadiene, and cyclododecadienol, were presented in rather low level which could lead to false negative results. The low-level transformation products should not be ignored because their toxicity was less assessment. This research highlighted identification of the low-level transformation products to reveal the complicated stereoselective biotransformation of HBCDs.


Assuntos
Retardadores de Chama , Rhodococcus , Biotransformação , Retardadores de Chama/análise , Retardadores de Chama/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Rhodococcus/metabolismo , Água do Mar
3.
Environ Health Perspect ; 130(5): 57002, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35503735

RESUMO

BACKGROUND: Abnormal placental development may result in adverse pregnancy outcomes and metabolic diseases in adulthood; however, it remains unknown whether and how xenobiotics affect human placentation. OBJECTIVES: This study aimed to screen and identify placentation-disrupting chemicals in commonly used organophosphate flame retardants (OPFRs) and, if identified, to investigate potential adverse effects on placentation in relation to adverse pregnancy outcomes and metabolic disorder in offspring in mice. METHODS: We devised a high-throughput immunofluorescence screening assay based on human trophoblast organoids and used it to screen OPFRs that inhibit the proliferation of organoids. One identified chemical was assessed for its effects on placentation by evaluating villous cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts using immunofluorescence and a mitochondrial stress test after 2 d of exposure. A 10-d exposure study was further performed to observe the dynamic effect of the OPFR on the structure of the organoids. RNA-sequencing and western blotting experiments were performed to explore the associated pathways, and a potential binding protein was identified by immunoprecipitation and in vitro kinase activity assays. Animal studies were performed to determine whether the findings in organoids could be replicated in mice and to observe adverse pregnancy outcomes. RESULTS: The proliferation of organoids exposed to three aryl-OPFRs was significantly lower than the proliferation of control organoids. Further analysis demonstrated that one such chemical, 2-ethylhexyl-diphenyl phosphate (EHDPP), disrupted placentation in organoids. Mechanistically, EHDPP interfered with insulin-like growth factor 1 receptor (IGF1R) to inhibit aerobic respiration. Mice exposed to EHDPP at a physiological human concentrations exhibited immature and mature placental disorders, which correlated with fetal growth restriction, implantation failure, stillbirth, and impaired glucose tolerance. CONCLUSIONS: The human trophoblast organoid model showed that the commonly used OPFRs disrupted placentation via IGF1R, indicating that its use may contribute to adverse pregnancy outcomes and metabolic disorders in offspring. https://doi.org/10.1289/EHP10273.


Assuntos
Retardadores de Chama , Adulto , Animais , Feminino , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Humanos , Camundongos , Organoides , Organofosfatos/metabolismo , Organofosfatos/toxicidade , Placenta , Placentação , Gravidez , Resultado da Gravidez , Trofoblastos
4.
Toxicology ; 474: 153211, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35595029

RESUMO

As a new type of flame retardant, Organic Phosphate Flame Retardant has been widely used worldwide. The purpose of our research is to determine the neurotoxicity of Tris (1,3-dichloroisopropyl) phosphate (TDCPP) to Caenorhabditis elegans and its mechanism. L1 larvae wild-type C. elegans were exposed to different concentrations of TDCPP, and the effects on motor behavior (head thrashes, body bends, pumping times, chemotaxis index), ROS levels, and p38MAPK signaling pathway-related gene expression levels were measured. Three transgenic nematode strains, BZ555, DA1240, and EG1285, were also used to study the effects of TDCPP on nematode dopamine neurons, glutamate neurons, and GABA neurons. The results showed that TDCPP can inhibit the head thrashes and body bends of the nematode, reduce dopamine production, increase the level of ROS in the body, and affect the expression of genes related to the p38MAPK signaling pathway. We next employed ROS production and motor behavior as toxicity assessment endpoints to determine the involvement of p38 MAPK signaling in the regulation of response to TDCPP. The results showed that the nematodes with low expression of pmk-1 were less sensitive to the TDCPP. It was suggested that TDCPP had neurotoxicity and regulated neurotoxicity to C. elegans by activating the p38-MAPK signaling pathway. The research in this article provides important information for revealing the environmental health risks of organophosphorus flame retardants and their toxic mechanism of action.


Assuntos
Retardadores de Chama , Síndromes Neurotóxicas , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Organofosfatos/toxicidade , Compostos Organofosforados/toxicidade , Fosfatos , Espécies Reativas de Oxigênio
5.
Sci Total Environ ; 837: 155782, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35533854

RESUMO

Organophosphate esters (OPEs) are commonly applied as flame retardants and plasticizers. Toxicological studies suggest exposure effects on immune endpoints, raising concerns as infants' OPE exposures are elevated compared to older children and adults due to hand-to-mouth behavior and breastfeeding. Here, we sought to evaluate the immune responsiveness of infants to a neoantigen (e.g., a newly encountered antigen) in the presence of OPE exposures. As a proxy for immune responsiveness, children were given three doses of the Diphtheria, Tetanus, and Pertussis (DTaP) vaccine as recommended, and diphtheria and tetanus antibodies were evaluated in serum samples collected when children were 12 months old (n = 84). Titers were compared, based on maximum sample overlap, to measurements of OPE metabolites in spot urine samples collected before vaccination (age 2 months, n = 73) and at the time of antibody assessment (12 months of age, n = 46). Metabolites of two chlorinated OPEs were significantly associated with diminished antibodies for diphtheria and tetanus. A metabolite of tris (1,3-dichloroisopropyl)phosphate (TDCIPP) measured at 2 months was associated with decreased diphtheria antibodies (-0.07 IU/mL per log10 increase in metabolite). One metabolite of tris(2-chloroisopropyl)phosphate (TCIPP) measured at 12 months was associated with decreased tetanus antibodies (-0.57 IU/mL per log10 increase in metabolite). These results provide some preliminary insights for OPE exposure impacts on vaccine responses in early life and may have important implications for immune health through childhood and adulthood.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Exposição Ambiental , Organofosfatos , Adolescente , Adulto , Criança , Difteria/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Exposição Ambiental/efeitos adversos , Ésteres/metabolismo , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Humanos , Lactente , Pessoa de Meia-Idade , Organofosfatos/metabolismo , Organofosfatos/toxicidade , Plastificantes/metabolismo , Plastificantes/toxicidade , Tétano/prevenção & controle
6.
Chemosphere ; 299: 134463, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35367484

RESUMO

Triphenyl phosphate (TPHP) is a kind of organophosphorus flame retardants, and its use is increasing annually. However, the toxic effect associated with exposure to it has not been adequately investigated. Therefore, in this study, we determined the toxic dose of TPHP in the economic fish species, Cyprinus carpio. Acute and subacute toxicity tests were conducted, and the enrichment of TPHP in the gills, brain, intestines, and liver were determined by Liquid Chromatography-Mass Spectrometry, and the response of carp gut microbial community to TPHP stress was determined using 16 S rRNA gene high-throughput sequencing. Results showed that the 96-h LC50 of TPHP in carp was 7 mg/L. At the 7 d, the order of TPHP absorption was as follows (from highest to lowest): gills > intestine > liver > brain, but at the 28 d and the purification period, the order of TPHP absorption was brain > gills > intestine > liver. TPHP exposure at 3.5 mg/L decreased α-diversity of the intestinal microbial community (p < 0.05), and altered community composition, in particular the relative abundance of dominant microbial populations. Functional profiles of the microbial communities predicted based on 16 S rRNA gene data showed upregulation in the degradation of exogenous substances and energy metabolism of the TPHP-treated groups (p < 0.05), suggesting that intestinal microbial taxa play a role in reducing TPHP toxicity. The results provide insights that could facilitate risk assessments of TPHP pollutants in aquatic environments and the management of associated water pollution.


Assuntos
Carpas , Retardadores de Chama , Microbiota , Animais , Carpas/metabolismo , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Organofosfatos/toxicidade
7.
Phys Chem Chem Phys ; 24(16): 9203-9212, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35388852

RESUMO

The efficient decomposition of polybrominated diphenyl ethers (PBDEs), onetime prevalent flame retardants, is central to the reduction of their harmful effects on human health. PBDE photodecomposition is a promising method, but its mechanism and products are not well understood. The photoexcitation dynamics of 3- and 4-bromodiphenyl ethers (BDE-2 and BDE-3) in CD3CN were studied from 0.3 ps to 10 µs using time-resolved infrared spectroscopy. An excitation at 267 nm dissociated the Br atom from BDE-2 and BDE-3 within 0.3 ps and 14 ± 3 ps, respectively, producing a radical compound (R) and a Br atom. About 85% of R formed an intermediate (IM) that weakly interacted with the Br atom and the surrounding CD3CN solvent in 7-12 ps. The remaining R separated from the dissociated Br and underwent slow geminate rebinding (GR) with Br within 35 to 54 ns. The IM competitively engaged in GR with the interacting Br in 40-60 ps or formed CD3CN-bound radical compounds (RS) in 100-130 ps. The RS further degraded via either the dissociation of CD3-producing a cyano-bound diphenyl ether (DE) in 150 or 550 ns-or the deuterium abstraction of CD3CN in 180 or 430 ns-producing a deuterated DE. Overall, 33 ± 3 (22 ± 3)% of the photoexcited BDE-2 (BDE-3) decomposed in CD3CN under 267 nm excitation. Efficient binding of the CD3CN solvent to R deterred the yield-diminishing GR and slowed the rate of product formation. The observed photoexcitation dynamics of BDE suggest methods for the efficient decomposition of PBDE.


Assuntos
Retardadores de Chama , Acetonitrilas , Retardadores de Chama/metabolismo , Humanos , Solventes , Análise Espectral
8.
Water Res ; 218: 118464, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35461102

RESUMO

Tris(2-chloroethyl) phosphate (TCEP) is of growing concern because of its ubiquitous occurrence, potential toxicity, and persistence in the environment. In this study, two efficient TCEP degradation consortia (AT1 and AT3) were developed and were able to completely hydrolyze TCEP within 20-25 h. Rhizobiales was identified as the key degrader in both consortia, because Rhizobiales-related phosphoesterase genes were enriched by one to two orders of magnitude when the carbon source was changed from acetate to TCEP. In addition, the increase in Rhizobiales abundance was related to the development of TCEP degradation. The isolation of Xanthobacter strains confirmed the efficient TCEP and bis(2-chloroethyl) phosphate (BCEP) degradation of Rhizobiales. The higher abundances of phosphoesterase genes affiliated with Rhizobiales genera (Bradyrhizobium and Ancylobacter), Cytophagales genus (Spirosoma), Sphingobacteriales genus (Pedobacter), and Burkholderia genus (Methylibium), may be related to the faster TCEP degradation in AT3, while the higher abundance of Rhizobiales genus (Hyphomicrobium)-related phosphodiesterase (PDE) genes may contribute to the faster BCEP degradation in AT1. The stepwise hydrolysis of TCEP was likely catalyzed by different bacterial guilds, which was confirmed by the coculture of TCEP- and BCEP-degrading isolates and highlighted the importance of synergistic interactions during TCEP degradation.


Assuntos
Retardadores de Chama , Fosfinas , Retardadores de Chama/metabolismo , Organofosfatos , Fosfatos
9.
Sci Total Environ ; 833: 155249, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35427616

RESUMO

Tetrabromobisphenol A (TBBPA) and its debromination (∑BBPA) and O-methylation (∑MeO-TBBPA) products were widely detected in matched sediments, fish, and whelks samples collected from a typical electronic waste (e-waste) dismantling site in Southern China, with concentrations ranging from 19.8 to 1.52 × 104, 8.05 to 1.84 × 103, and 0.08 to 11.9 ng/g dry weight in sediments, and 6.96 to 1.97 × 105, 3.84 to 7.07 × 103, and 3.42 to 472 ng/g lipid in biotas, for TBBPA, ∑BBPA, and ∑MeO-TBBPA, respectively. Significantly higher concentrations of these targets were found in samples collected close to the e-waste site, indicating their potential e-waste sources. Tri-BBPA was the most abundant debromination products in sediments, whereas diMeO-TBBPA was the dominant O-methylation product in biotas. Relatively higher levels of diMeO-TBBPA found in liver and kidneys, suggesting these chemicals might be mainly derived from the in vivo biotransformation. Furthermore, significantly higher biota-sediment accumulation factor values were found for diMeO-TBBPA than these of TBBPA, indicating that O-methylation would increases their accumulation in aquatic organisms. Our study provides insights into the accumulation and biotransformation of TBBPA in aquatic systems. Further studies should pay attention to the occurrence as well as potential health risks of these transformation products.


Assuntos
Resíduo Eletrônico , Retardadores de Chama , Bifenil Polibromatos , Animais , Peixes/metabolismo , Retardadores de Chama/metabolismo , Metilação , Bifenil Polibromatos/análise
10.
Sci Total Environ ; 826: 154145, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35227722

RESUMO

Due to the regulation of hexabromocyclododecane (HBCD), much attention has been paid to its potential substitutes, 1,2-dibromo-4-(1,2-dibromoethyl) cyclohexane (DBE-DBCH) and 1,2,5,6-tetrabromocyclooctane (TBCO). DBE-DBCH and TBCO contain several diastereomers and enantiomers, which may exhibit different environmental behaviors and biological effects. In this study, the accumulation and depuration of individual DBE-DBCH and TBCO diastereomers by earthworms (Eisenia fetida) from diastereomer-contaminated soils were evaluated. The accumulation and depuration kinetics of DBE-DBCH and TBCO diastereomers followed one-compartment first-order kinetics. The biota soil accumulation factor (BSAF) of ß-DBE-DBCH (2.74 goc glip-1) was 1.26 times that of α-DBE-DBCH (2.18 goc glip-1), while the BSAF of ß-TBCO (2.15 goc glip-1) was 1.62 times that of α-TBCO (1.3 goc glip-1), showing the diastereomer-specific accumulation of DBE-DBCH and TBCO. DBE-DBCH and TBCO diastereomers appeared to be transformed in earthworm-soil systems; however, no evidence of bioisomerization of the four diastereomers in earthworms was found, and no potential metabolites of debromination and hydroxylation were detected. Furthermore, the selective enrichment of E1-α-DBE-DBCH and E1-ß-DBE-DBCH (E1 represents the first enantiomer eluted) occurred in earthworms as the enantiomer fractions (EFs) for α-DBE-DBCH (0.562-0.763) and ß-DBE-DBCH (0.516-0.647) were significantly greater than those in the technical products (0.501 for α-DBE-DBCH and 0.497 for ß-DBE-DBCH, p < 0.05), especially in the depuration stage. The results demonstrated the diastereomer- and enantiomer-selective accumulation of DBE-DBCH and the diastereomer-selective accumulation of TBCO in the earthworm.


Assuntos
Retardadores de Chama , Oligoquetos , Poluentes do Solo , Animais , Cicloexanos , Ciclo-Octanos , Retardadores de Chama/metabolismo , Hidrocarbonetos Bromados , Oligoquetos/metabolismo , Solo , Poluentes do Solo/metabolismo
11.
J Hazard Mater ; 431: 128517, 2022 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-35217347

RESUMO

Organic phosphorus flame retardants (OPFRs), as a new type of emerging contaminant, have drawn great attention over the last few years, due to their wide distribution in aquatic environments and potential toxicities to humans and living beings. Various treatment methods have been reported to remove OPFRs from water or wastewater. In this review, the performances and mechanisms for OPFRs removal with different methods including adsorption, oxidation, reduction and biological techniques are overviewed and discussed. Each technique possesses its advantage and limitation, which is compared in the paper. The degradation pathways of typical OPFRs pollutants, such as Cl-OPFRs, alkyl OPFRs and aryl OPFRs, are also reviewed and compared. The degradation of those OPFRs depends heavily upon their structures and properties. Furthermore, the implications and future perspectives in such area are discussed. The review may help identify the research priorities for OPFRs remediation and understand the fate of OPFRs during the treatment processes.


Assuntos
Poluentes Ambientais , Retardadores de Chama , Retardadores de Chama/metabolismo , Humanos , Organofosfatos/metabolismo , Fósforo , Água
12.
Chemosphere ; 295: 133862, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35124078

RESUMO

Nanoparticles like nano-TiO2 are suspected to influence the bioavailability and toxicity of co-existing organic or inorganic pollutants differently in aquatic environment. Recently, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardants (NBFRs) with potential lipid-metabolism disruptive effects, has been detected prevalently in multiple environments including where nano-TiO2 was also observed. However, their interaction in aqueous phase and modification of nano-TiO2 on biological processes and toxicity of TBPH at environmental relevant levels remain unknown. Accordingly, we exposed zebrafish embryos to TBPH (1, 10, 100 and 1000 µg/L) alone or with nano-TiO2 (100 µg/L) until 72 h post-fertilization (hpf) with emphasis on their physicochemical interactions in solutions and variations of bioavailability and toxicity regarding lipid metabolism in vivo. Zeta potential, fourier transform infrared (FTIR) spectroscopy and TEM-EDS revealed adsorption and agglomeration between TBPH and nano-TiO2in vitro. Decreased body contents of nano-TiO2 and TBPH implied a reduction of TBPH in bioavailability. The enhanced lipid metabolism and reduced fat storage by TBPH alone were all alleviated by co-exposure to nano-TiO2. The overall results indicate that nano-TiO2 adsorbed TBPH to form size-enlarged agglomerates and led to decreased bioavailability and consequently mitigated lipid metabolism disorders in developing zebrafish embryo/larvae.


Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Disponibilidade Biológica , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Titânio/toxicidade , Peixe-Zebra/metabolismo
13.
J Steroid Biochem Mol Biol ; 219: 106079, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35143981

RESUMO

Brominated flame retardants (BFRs) are persistent environmental pollutants, allowing a constant human exposure which carries several health risks, including the occurrence of breast cancer and vitamin D deficiency. Vitamin D inhibits cell growth and is negatively associated with breast cancer risk. The effect of BFRs in breast cancer and vitamin D pathway is still poorly understood. MCF-7 cells were treated with hexabromocyclododecane (HBCD), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), hexabromobenzene (HBB) and pentabromotoluene (PBT) using short and long-term exposure protocols. Viability, proliferation, migration, cell cycle and gene expression were assessed. Gene expression of hVDBP and hCYP2R1 was also evaluated in hepatocytes. Long-term exposure of MCF-7 cells to HBB increased cell proliferation and migration, consequently increasing MMP-9 expression. The vitamin D pathway was also altered by BFRs: cells appeared less prepared to activate and transport vitamin D and the signaling, action and inactivation mechanisms were diminished in the presence of BFRs. Untreated MCF-7 cells showed cell cycle arrest in phase G0/G1 in the presence of activated vitamin D. However, when MCF-7 cells were exposed to BFRs, cell cycle was arrested in phase G2/M, possibly due to DNA damage. Nonetheless, calcitriol seems to be able to mitigate the effect of some BFRs exposure, e.g. PBT.


Assuntos
Neoplasias da Mama , Retardadores de Chama , Feminino , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/metabolismo , Humanos , Células MCF-7 , Vitamina D/farmacologia
14.
Environ Int ; 160: 107081, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35021149

RESUMO

As an important organophosphate flame retardant, tris(1-chloro-2-propyl)phosphate (TCPP) is ubiquitous in the environment leading to inevitable human exposure. However, there is a paucity of information regarding its acute/chronic effects on obesity, lipid homeostasis, and hepatocellular carcinoma, especially regarding the underlying molecular mechanisms in humans. Herein, we investigated the effects of TCPP exposure (5-25 mg/L) on lipid homeostasis in larval and adult zebrafish (Danio rerio). TCPP exposure caused remarkable lipid-metabolism dysfunction, which was reflected in obesity and excessive lipid accumulation in zebrafish liver. Mechanistically, TCPP induced the over-expression of adipogenesis genes and suppressed the expression of fatty-acid ß-oxidation genes. Consequently, excess lipid synthesis and deficient expenditure triggered oxidative damage and an inflammation response by disrupting the antioxidant system and over-expressing proinflammatory cytokine. Based on high-throughput transcriptome sequencing, we found that TCPP exposure led to enrichment of several pathways involved in lipid metabolism and inflammation, as well as several genes related to pathways of cancer. Notably, increasing expressions of Ki-67 and 53BP1 proteins, which are reliable biomarkers for recognition and risk prediction of cellular proliferation in cancer cells, were observed in liver tissues of adult zebrafish. These results imply that chronic TCPP exposure triggers a potential risk of hepatocellular carcinogenesis (HCC) progression. Collectively, these findings offer new insights into our mechanistic understanding for the health effects of organophosphorus flame retardants on humans.


Assuntos
Carcinoma Hepatocelular , Retardadores de Chama , Neoplasias Hepáticas , Animais , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Inflamação , Larva , Metabolismo dos Lipídeos , Organofosfatos/metabolismo , Organofosfatos/toxicidade , Compostos Organofosforados , Estresse Oxidativo , Fosfatos/metabolismo , Peixe-Zebra/metabolismo
15.
Environ Sci Technol ; 56(4): 2519-2528, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35075897

RESUMO

3,3',5,5'-Tetrabromobiphenyl (BB-80) was once used as additive flame retardants. Whether its early exposure and discontinued exposure alter thyroid function remains unknown. We investigate adverse effects after early-life exposure and discontinued exposure to BB-80 and hydroxylated BB-80 (OH-BB-80) on thyroid hormone (TH) levels, thyroid tissue, and transcriptome profiles in zebrafish larvae. BB-80 at 10 µg/L induces pathological changes of thyroid with reduced thyroid follicles in larvae (P < 0.05), whereas OH-BB-80 significantly increases T4 and T3 contents (1.8 and 2.5 times of the control, P < 0.05) at 14 days postfertilization (dpf) without morphological thyroid alterations. BB-80 and OH-BB-80 cause transcriptome aberrations with key differentially expressed genes involved in the disruption of TH synthesis and signal transduction (BB-80 at 14 dpf) or TH pathway activation (OH-BB-80 at 21 dpf). After 7 days of discontinued exposure, thyroglobulin (tg) and thyroid peroxidase (tpo) genes are downregulated (P < 0.05) by 52 and 48% for BB-80 and by 49 and 39% for OH-BB-80, respectively; however, the whole-body TH levels fail to fully recover, and the locomotor activity is impaired more by BB-80. Our results indicate significant adverse impacts of BB-80 and OH-BB-80 on TH homeostasis and thyroid function of zebrafish.


Assuntos
Retardadores de Chama , Poluentes Químicos da Água , Animais , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Larva/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
16.
Environ Res ; 205: 112494, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34890595

RESUMO

As a typical brominated flame retardants (BFRs), 2,4,6-tribromophenol (TBP) has serious hazard to the environmental health and its environmental fate has attracted considerable attention. Dehalogenation reaction plays key role in microbial TBP degradation and detoxification. So far, several halophenols-degrading enzymes have been reported to transform their substrate by oxidative dehalogenation; however, the molecular and biochemistry characterization of microbial hydrolytic dehalogenation is limited. In this study, Cupriavidus sp. CNP-8 with high TBP degradation activity was found to degrade TBP via an obviously differnet pathway as compared to other reported TBP-degraders. The transcription of hnp genes were significantly upregulated with TBP stimulation, indicating their involvment in TBP degradation. Enzymatic assays with 18O-labeling experiments showed that HnpAB, a two-component FAD-dependent monooxygenase, transformed TBP via consecutive oxidative and hydrolytic debromination reactions with the formation of 6-bromo-1,2,4-benzenetriol (BBT) as the ring-cleavage substrate. The function of the BBT ring-cleavage enzyme (HnpC) was also characterized both in vitro and in vivo. This finding provides new molecular mechanism of microbial detoxification of TBP and novel information of the environmental fate of this BFRs. Furthermore, to investigate the frequency of this novel dehalogenation mechanism in microbes, we also analyzed the distribution as well as the genetic structure of the hnpABC cluster by comparative genomics. Although hnpA homolog is distributed in several bacterial genera including Cupriavidus, Paraburkholderia, Variovorax and Streptomyces, the complete hnpABC cluster is only retrieved from Cupriavidus and strictly conservative in the genomes. This indicated that Cupriavidus have unique evolutionary pattern in acquiring the hnpABC to degrade TBP and its analogs, enhancing our understanding of the microbial adaptive evolution in halophenols-contaminated environment.


Assuntos
Retardadores de Chama , Fenóis , Biodegradação Ambiental , Retardadores de Chama/metabolismo , Estresse Oxidativo , Fenóis/metabolismo
17.
Environ Sci Pollut Res Int ; 29(12): 17087-17102, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34655032

RESUMO

Flame retardants are compounds added to a high diversity of polymers used in electronics and furniture to decrease the risk of combustion. Decabromodiphenyl ether (BDE-209) is a polybrominated diphenyl ether (PBDE) congener still used worldwide, while 2, 4, 6-tribromophenol(TBP) is a PBDE metabolite used as a pesticide and flame retardant for wood conservation. These compounds have lipophilic properties and are easily bioaccumulated in the food chain. In the current study, the acute and chronic toxicity of BDE-209 and TBP was evaluated in Oreochromis niloticus through analyses of redox imbalance, neurotoxicity, and histopathological biomarkers after acute (24, 48, 72, and 96 h) and chronic (90 days) exposure to 0.5, 5, and 50 ng/g of the polybrominated compounds. The results showed effects on glutathione S-transferase(GST) activity and damage to biomolecules in both acute and chronic exposures. Liver histopathology and the ultrastructure of hepatocytes revealed alterations and damage in individuals from both experiments, but only BDE-209 led to neurotoxic effects. The current study revealed new endpoints related to polybrominated compounds in fish, highlighting the need to review the risk of exposure to biota.


Assuntos
Ciclídeos , Retardadores de Chama , Animais , Ciclídeos/metabolismo , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/metabolismo , Éteres Difenil Halogenados/toxicidade , Humanos , Fígado
18.
Environ Toxicol Chem ; 41(3): 739-747, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34913512

RESUMO

Organophosphate flame retardants (OPFRs) are used in a variety of products such as clear coats, resins, and plastics; however, research into their toxicological effects is limited. p-Tert-butylphenyl diphenyl phosphate (BPDP) and isopropylphenyl phosphate (IPPP) are two OPFRs that were prioritized for whole-animal toxicological studies based on observed effects in cultured avian hepatocytes in a previous study. The present study investigates the toxicity of BPDP and IPPP in chicken embryos at different developmental stages by evaluating morphological and gene expression endpoints. Chicken eggs were exposed via air cell injection to 0-250 µg/g (nominal) of either compound and then artificially incubated. At day 11 (midincubation), liver samples were collected for mRNA expression analysis; and at day 20 (1 day prehatch), morphological measurements and liver samples for transcriptomic evaluation were collected. At 250 µg/g, gallbladder size was significantly reduced for both compounds, head/bill length and tarsus length were significantly decreased, and liver somatic index was significantly increased following IPPP exposure only. No effects on mortality were observed up to the highest administered concentration for either chemical. Using a ToxChip polymerase chain reaction array, we report significant differences in hepatic gene expression for both compounds and time points; the most pronounced transcriptomic effects occurred at midincubation. Genes related to xenobiotic metabolism, bile acid/cholesterol regulation, and oxidative stress were significantly dysregulated. Given these changes observed throughout avian embryonic development, further research into the long-term effects of BPDP and IPPP are warranted, especially as they pertain to liver cholestasis. Environ Toxicol Chem 2022;41:739-747. © 2021 Her Majesty the Queen in Right of Canada. Environmental Toxicology and Chemistry © 2021 SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.


Assuntos
Galinhas , Retardadores de Chama , Animais , Embrião de Galinha , Galinhas/metabolismo , Feminino , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Fígado/metabolismo , Organofosfatos/toxicidade , Fosfatos , Transcriptoma
19.
Chem Commun (Camb) ; 57(53): 6475-6478, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34105548

RESUMO

Engineering of a promiscuous lactonase via semi-rational evolution gave a 1007-fold improvement in its catalytic activity in the degradation of triphenyl phosphate (TPHP). TPHP is a typical bulky organophosphate flame retardant (OPFR) and is widely used in industry. To the best of our knowledge, this is the first artificial enzyme capable of degrading OPFRs.


Assuntos
Hidrolases de Éster Carboxílico/química , Hidrolases de Éster Carboxílico/metabolismo , Domínio Catalítico , Retardadores de Chama/metabolismo , Organofosfatos/metabolismo , Hidrolases de Éster Carboxílico/genética , Engenharia de Proteínas , Especificidade por Substrato
20.
J Perinat Med ; 49(4): 439-447, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33554574

RESUMO

OBJECTIVES: Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. METHODS: Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. RESULTS: We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. CONCLUSIONS: These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.


Assuntos
Éteres Difenil Halogenados , Primeiro Trimestre da Gravidez/sangue , Nascimento Prematuro , Doenças da Glândula Tireoide , Tireotropina/sangue , Adulto , Estudos de Coortes , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/análise , Disruptores Endócrinos/sangue , Feminino , Retardadores de Chama/efeitos adversos , Retardadores de Chama/análise , Retardadores de Chama/metabolismo , Éteres Difenil Halogenados/efeitos adversos , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/sangue , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/diagnóstico , Estados Unidos/epidemiologia
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