Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.268
Filtrar
1.
Chemosphere ; 310: 136808, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36223822

RESUMO

Flame retardants, such as Tetrabromobisphenol A (TBBPA), Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tributyl phosphate (TBP), are frequently detected in surface water. However, the effects of FRs exposure on aquatic organisms especially freshwater microalgae are still unclear. In this study, the toxicities of TBBPA, TDCPP and TBP to microalgae Chlorella sorokiniana, in terms of growth inhibition, photosynthetic activity inhibition and oxidative damage, were investigated, and according ecological risks were assessed. The results showed that TBBPA, TDCPP and TBP had inhibitory effects on C. sorokiniana, with 96 h EC50 (concentration for 50% of maximal effect) values of 7.606, 41.794 and 49.996 mg/L, respectively. Fv/Fm decreased as the increase of exposure time under 15 mg/L TBBPA. Under 50 mg/L TDCPP and 80 mg/L TBP exposure, Fv/Fm decreased significantly after 24 h. However, Fv/Fm rose after 96 h, indicating that the damaged photosynthetic activity was reversible. The content of chlorophyll a decreased, as the increase of TBBPA concentration from 3 to 15 mg/L. However, chlorophyll a increased first and then decreased, as the increase of TDCPP and TBP concentrations from 0 to 50 mg/L and 0-80 mg/L, respectively. Results indicated that C. sorokiniana could use the phosphorus of TDCPP and TBP to ensure the production of chlorophyll a. The risen content of reactive oxygen species, malondialdehyde as well as superoxide dismutase activity indicated that exposure to FRs induced oxidative stress. Additionally, the risk quotients showed that tested FRs had ecological risks in natural waters or wastewaters. This study provides insights into the toxicological mechanisms of different FRs toward freshwater microalgae for better understanding of according environmental risks.


Assuntos
Chlorella , Retardadores de Chama , Microalgas , Retardadores de Chama/toxicidade , Clorofila A , Compostos Organofosforados/toxicidade , Água Doce
2.
Chemosphere ; 310: 136924, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36272632

RESUMO

Tetrabromobisphenol A (TBBPA) is widely used in industrial production as a halogenated flame retardant (HFR). Its substitutes and derivatives are also commonly employed as HFRs. Consequently, they can be frequently detected in environmental and human samples. The potential developmental toxicity of TBBPA and its analogs, particularly to the human liver, is still controversial or not thoroughly assessed. Therefore, in this study, we focused on the early stages of human liver development to explore the toxic effects of those HFRs, by using a human embryonic stem cell liver differentiation model. We concluded that nanomolar treatments (1, 10, and 100 nM) of those pollutants may not exert significant interference to liver development and functions. However, at 5 µM doses, TBBPA and its analogs severely affected liver functions, such as glycogen storage, and caused lipid accumulation. Furthermore, TBBPA-bis(allyl ether) showed the most drastic effects among the six compounds tested. Taken together, our findings support the view that TBBPA can be used safely, provided its amounts are strictly controlled. Nonetheless, TBBPA alternatives or derivatives may exhibit stronger adverse effects than TBBPA itself, and may not be safer choices for manufacturing applications when utilized in a large and unrestricted way.


Assuntos
Retardadores de Chama , Febre Hemorrágica com Síndrome Renal , Células-Tronco Embrionárias Humanas , Bifenil Polibromatos , Humanos , Bifenil Polibromatos/toxicidade , Retardadores de Chama/toxicidade , Fígado
3.
J Environ Sci (China) ; 124: 291-299, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182138

RESUMO

Many environmental contaminants could be transmitted from parents and generate impairments to their progeny. The 2,4,6-tribromophenol (TBP), a novel brominated flame retardant which has been frequently detected in various organisms, was supposed to be bioaccumulated and intergenerational transmitted in human beings. Previous studies revealed that TBP could disrupt thyroid endocrine system in zebrafish larvae. However, there is no available data regarding the parental and transgenerational toxicity of this contaminant. Thus, in this study adult zebrafish were exposed to environmental contaminated levels of TBP for 60 days to investigate the parental and transgenerational impairments on thyroid endocrine system. Chemical analysis verified the bioaccumulation of TBP in tested organs of parents (concentration: liver>gonads>brain) and its transmission into eggs. For adults, increased thyroid hormones, disturbed transcriptions of related genes and histopathological changes in thyroid follicles indicate obvious thyroid endocrine disruptions. Transgenerational effects are indicated by the increased thyroid hormones both in eggs (maternal source) and in developed larvae (newly synthesized), as well as disrupted transcriptional profiles of key genes in HPT axis. The overall results suggest that the accumulated TBP could be transmitted from parent to offspring and generate thyroid endocrine disruptions in both generations.


Assuntos
Disruptores Endócrinos , Retardadores de Chama , Poluentes Químicos da Água , Animais , Disruptores Endócrinos/toxicidade , Retardadores de Chama/toxicidade , Humanos , Larva , Fenóis , Glândula Tireoide , Hormônios Tireóideos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
4.
Front Endocrinol (Lausanne) ; 13: 997304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277707

RESUMO

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardant organohalogen pollutants that act as endocrine/neuroendocrine disrupting chemicals (EDCs). In humans, exposure to brominated flame retardants (BFR) or other environmentally persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and novel organophosphate flame retardants has been associated with increasing trends of diabetes and metabolic disease. However, the effects of PBDEs on metabolic processes and their associated sex-dependent features are poorly understood. The metabolic-disrupting effects of perinatal exposure to industrial penta-PBDE mixture, DE-71, on male and female progeny of C57BL/6N mouse dams were examined in adulthood. Dams were exposed to environmentally relevant doses of PBDEs daily for 10 weeks (p.o.): 0.1 (L-DE-71) and 0.4 mg/kg/d (H-DE-71) and offspring parameters were compared to corn oil vehicle controls (VEH/CON). The following lipid metabolism indices were measured: plasma cholesterol, triglycerides, adiponectin, leptin, and liver lipids. L-DE-71 female offspring were particularly affected, showing hypercholesterolemia, elevated liver lipids and fasting plasma leptin as compared to same-sex VEH/CON, while L- and H-DE-71 male F1 only showed reduced plasma adiponectin. Using the quantitative Folch method, we found that mean liver lipid content was significantly elevated in L-DE-71 female offspring compared to controls. Oil Red O staining revealed fatty liver in female offspring and dams. General measures of adiposity, body weight, white and brown adipose tissue (BAT), and lean and fat mass were weighed or measured using EchoMRI. DE-71 did not produce abnormal adiposity, but decreased BAT depots in L-DE-71 females and males relative to same-sex VEH/CON. To begin to address potential central mechanisms of deregulated lipid metabolism, we used RT-qPCR to quantitate expression of hypothalamic genes in energy-regulating circuits that control lipid homeostasis. Both doses of DE-71 sex-dependently downregulated hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON. In contrast, exposed male offspring displayed upregulated Stat3 and Mc4r. Intestinal barrier integrity was measured using FITC-dextran since it can lead to systemic inflammation that leads to liver damage and metabolic disease, but was not affected by DE-71 exposure. These findings indicate that maternal transfer of PBDEs disproportionately endangers female offspring to lipid metabolic reprogramming that may exaggerate risk for adult metabolic disease.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Retardadores de Chama , Bifenilos Policlorados , Animais , Feminino , Masculino , Camundongos , Gravidez , Adiponectina , Proteína Relacionada com Agouti , Colesterol , Óleo de Milho , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Homeostase , Leptina , Camundongos Endogâmicos C57BL , Organofosfatos , Poluentes Orgânicos Persistentes , Triglicerídeos , Fatores Sexuais
5.
Environ Pollut ; 314: 120317, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36191796

RESUMO

Ecotoxicological effects of photolytic degradation mixtures of the two brominated flame retardants PolymericFR and Tetrabromobisphenol A-bis (2,3-dibrom-2-methyl-propyl) Ether (TBBPA-BDBMPE) have been studied in vitro and in vivo. Both substances were experimentally degraded separately by exposure to artificial UV-light and the resulting degradation mixtures from different time points during the UV-exposure were applied in ecotoxicological tests. The in vitro investigation showed no effects of the degraded flame retardants on the estrogenic and androgenic receptors via the CALUX (chemically activated luciferase gene expression) assay. Short-term exposures (up to 96 h) of Lumbriculus variegatus lead to temporary physiological reactions of the annelid. The exposure to degraded PolymericFR lead to an increased activity of Catalase, while the degradation mixture of TBBPA-BDBMPE caused increases of Glutathione-S-transferase and Acetylcholine esterase activities. Following a chronic exposure (28 d) of L. variegatus, no effects on the growth, reproduction, fragmentation and energy storage of the annelid were detected. The results indicate that the experimental degradation of the two flame retardants causes changes in their ecotoxicological potential. This might lead to acute physiological effects on aquatic annelids, which, however, do not affect the animals chronically according to our results.


Assuntos
Retardadores de Chama , Hidrocarbonetos Bromados , Naled , Bifenil Polibromatos , Animais , Retardadores de Chama/toxicidade , Retardadores de Chama/metabolismo , Catalase , Acetilcolina , Bifenil Polibromatos/toxicidade , Bifenil Polibromatos/química , Polímeros , Éteres , Transferases , Glutationa , Esterases , Hidrocarbonetos Bromados/análise
6.
Ecotoxicol Environ Saf ; 246: 114165, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36228355

RESUMO

Decabromodiphenyl ethane (DBDPE) is a typical flame retardant found in various electrical and textile items. DBDPE is abundantly available in the surrounding environment and wild animals based on its persistence and bioaccumulation. DBDPE has been shown to cause apoptosis in rat spermatogenic cells, resulting in reproductive toxicity. However, the toxicity of DBDPE on the male reproductive system and the potential mechanisms are still unclear. This study evaluated the effect of DBDPE on the reproductive system in male SD rats and demonstrated the potential mechanisms of reproductive toxicity. DBDPE (0, 5, 50, and 500 mg/kg/day) was administered via gavage to male SD rats for 28 days. DBDPE caused histopathological changes in the testis, reduced sperm quantity and motility, and raised the malformation rate in rats, according to the findings. Furthermore, it caused DNA damage to rat testicular cells. It inhibited the expressions of spermatogenesis-and oogenesis-specific helix-loop-helix transcription factor 1 (Sohlh1), piwi-like RNA-mediated gene silencing 2 (MILI), cyclin-dependent kinase 2 (CDK2), and CyclinA, resulting in meiotic failure, as well as the expressions of synaptonemal complex proteins 1 and 3 (SYCP1 and SYCP3), leading to chromosomal association disorder in meiosis and spermatocyte cycle arrest. Moreover, DBDPE induced glycolipid metabolism disorder and activated mitochondria-mediated apoptosis pathways in the testes of SD rats. The quantity and quality of sperm might be declining due to these factors. Our findings offer further evidence of the harmful impact of DBDPE on the male reproductive system.


Assuntos
Retardadores de Chama , Sêmen , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Bromobenzenos , Retardadores de Chama/toxicidade , Glicolipídeos
7.
Ecotoxicol Environ Saf ; 246: 114186, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36244175

RESUMO

Tri-(2,3-dibromopropyl) isocyanate (TBC), a newly brominated flame retardant, is widely used in the synthesis of flame retardant materials with characteristics of persistent organic pollutants. To obtain environmental exposure risks of TBC, Wistar rats and HepG2 cell were used for in vivo and in vitro studies on the toxicity of TBC and relevant ecotoxicological mechanisms of apoptosis. 80 Wistar rats were randomly selected and divided into four exposure groups (0, 0.313, 0.625, 1.250) g/(kg·bw) TBC, half male and half female, with oral administration for 28 days. Wistar rats exhibited appetite loss, weight loss, and dull hair with increasing period of TBC exposure. The pathological examinations revealed the most severe damage of liver and the ratio of liver/body weight of 35.497 × 10-3 for high-dosed group (1.250 g/kg·bw) was higher than that of 32.792 × 10-3 for control group in female rats with identical trend in male rats. The above indicators was fairly consistent with the serum test results which further confirmed the liver to be the target organ. The exposure dosages of HepG2 cell were (0, 12.5, 25, 50) µg/mL, individually. The HepG2 cells exposed to TBC for 72 h displayed hazy cell contour and decreased density of cell growth. And there was an inhibition detected by MTT assay, where the maximum inhibition rate was 19.93% under the dose of 50 µg/mL TBC. Apoptosis rate detected by flow cytometry which was demonstrated to be positively correlated to exposure dosage of TBC. The apoptosis rates of the low, medium and high dose groups of TBC exposure were (1.082 ± 0.109) %, (3.017 ± 0.09) % and (6.813 ± 0.233) %, individually. Targeted genes and corresponding protein expressions that triggering apoptosis both in vivo and in vitro were significantly altered. Overall, this work discloses the impacts of TBC exposure on hepatotoxicity, which provides new insights for chemical risk assessments of accelerate cell apoptosis via mitochondrial and death receptor pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Retardadores de Chama , Animais , Feminino , Masculino , Ratos , Retardadores de Chama/toxicidade , Ratos Wistar , Receptores de Morte Celular , Triazinas/toxicidade
8.
Food Chem Toxicol ; 169: 113432, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36115506

RESUMO

Environmental monitoring data have indicated that three chlorinated organophosphorus flame retardants (Cl-OPFRs), including tris(2-chloroethyl)-phosphate (TCEP), tris(2-chloropropyl)-phosphate (TCPP), and tris(1,3-dichloro-2-propyl)-phosphate (TDCPP) are the predominant chemicals in various environmental matrices and exhibit reproductive endocrine disrupting activities. Currently, mitochondrial abnormality is a new paradigm for evaluating chemical-mediated cell dysfunction. However, a comprehensive correlation between these two aspects of Cl-OPFRs remains unclear. In this research, the effects of TCEP, TCPP, and TDCPP on progesterone production and mitochondrial impairment were investigated by using mouse Leydig tumor cells (mLTC-1). The half maximal inhibitory concentration (IC50) values at 48 h exposure indicated that the rank order of anti-androgenic activity was TDCPP > TCPP. Whereas, TCEP exhibited elevation of progesterone production. At concentrations close to IC50 of progesterone production by TCPP and TDCPP, the elevation of intracellular reactive oxygen species (ROS), depletion of mitochondrial membrane potential (MMP), reduction of cellular adenosine triphosphate (ATP) content, and alteration of mitochondrial structures was observed. In addition, the expression of main genes related to progesterone synthesis was dramatically down-regulated by TCPP and TDCPP treatments. These results imply that the inhibition effect of TCPP and TDCPP on progesterone production might be related to mitochondrial damage and down-regulated steroidogenic genes.


Assuntos
Monitoramento Ambiental , Retardadores de Chama , Mitocôndrias , Organofosfatos , Fosfinas , Progesterona , Animais , Camundongos , Trifosfato de Adenosina/metabolismo , Retardadores de Chama/toxicidade , Organofosfatos/toxicidade , Fosfinas/toxicidade , Progesterona/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tumor de Células de Leydig , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Monitoramento Ambiental/métodos
9.
Food Chem Toxicol ; 169: 113440, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36162615

RESUMO

Tris (2-chloroethyl) phosphate (TCEP), the most widely useful and most frequently detective organophosphate flame retardants in environment, has been shown potential relationship with adolescent weight. Probiotics is an effective therapy for metabolic diseases such as obesity and NAFLD with gut microbiota dysregulation. This study aims to explore the protective effects of probiotics against lipid metabolic disorder induced by chronic TCEP exposure and demonstrate the mechanism of this event. The data showed that dietary complex probiotics supplement attenuated TCEP-induced obesity, hyperlipidemia, liver dysfunction, and hepatic steatosis. In addition, dietary complex probiotics suppressed TCEP-promoted ileal FXR signaling, and upregulated hepatic FXR/SHP pathway inhibited by TCEP. Moreover, dietary complex probiotics stimulated PPARα-mediated lipid oxidation and suppressed SREBP1c/PPARγ-mediated lipid synthesis via regulation of FXR signaling. Therefore, this study indicates that dietary complex probiotics could protect against hepatic steatosis via FXR-mediated signaling pathway in TCEP-induced metabolism disorder in mice, resulting in attenuation of systemic lipid accumulation.


Assuntos
Retardadores de Chama , Doenças Metabólicas , Probióticos , Animais , Retardadores de Chama/toxicidade , Lipídeos , Camundongos , Obesidade , Organofosfatos , PPAR alfa , PPAR gama , Fosfatos , Fosfinas , Probióticos/farmacologia , Transdução de Sinais
10.
Environ Pollut ; 314: 120263, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36155225

RESUMO

Decabromodiphenyl ethane (DBDPE), as one of the most widely used new brominated flame retardants (NBFRs), can pose a potential threat to human health and the environment. An integrated transcriptome and proteome was performed for investigating the toxicological molecular mechanisms of Pleurotus ostreatus (P. ostreatus) during the biodegradation of DBDPE at the concentrations of 5 and 20 mg/L. A total of 1193/1018 and 92/126 differentially expressed genes/proteins (DEGs/DEPs) were found, respectively, with DBDPE exposure at 5 and 20 mg/L. These DEGs and DEPs were mainly involved in the cellular process as well as metabolic process. DEPs for oxidation-reduction process and hydrolase activity were up-regulated, and those for membrane, lipid metabolic process and transmembrane transport were down-regulated. The DEGs and DEPs related to some key enzymes were down-regulated, such as NADH dehydrogenase/oxidoreductase, succinate dehydrogenase, cytochrome C1 protein, cytochrome-c oxidase/reductase and ATP synthase, which indicated that DBDPE affected the oxidative phosphorylation as well as tricarboxylic acid (TCA) cycle. Cytochrome P450 enzymes (CYPs) might be involved in DBDPE degradation through hydroxylation and oxidation. Some stress proteins were induced to resist DBDPE toxicity, including major facilitator superfamily (MFS) transporter, superoxide dismutase (SOD), molecular chaperones, heat shock proteins (HSP20, HSP26, HSP42), 60S ribosomal protein and histone H4. The findings help revealing the toxicological molecular mechanisms of DBDPE on P. ostreatus, aiming to improve the removal of DBDPE.


Assuntos
Retardadores de Chama , Pleurotus , Trifosfato de Adenosina , Bromobenzenos/toxicidade , Citocromos c1 , Complexo IV da Cadeia de Transporte de Elétrons , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Proteínas de Choque Térmico , Histonas , Hidrolases , Lipídeos , NADH Desidrogenase , Proteoma , Proteômica , Proteínas Ribossômicas , Succinato Desidrogenase , Superóxido Dismutase , Transcriptoma , Ácidos Tricarboxílicos
11.
Ecotoxicol Environ Saf ; 244: 114044, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36055044

RESUMO

Decabromodiphenyl ethane (DBDPE), a widely used novel brominated flame retardant, is gaining concerns due to rapidly increased contents in various environmental and biota samples. In the present study, zebrafish (Danio rerio) embryos were exposed to 2.91, 9.71, 29.14 and 97.12 µg/L of DBDPE until 120 h post-fertilization (hpf) to investigate the potential developmental neurotoxicity and underlying mechanisms. Chemical analysis revealed concentration-dependently increased body burdens of DBDPE in zebrafish larvae, with bioaccumulation factors (BCFs) ranging from 414 to 726. Embryonic exposure to DBDPE caused hyperactivity without affecting the development of secondary motoneuron axons and muscle fibers. However, further results implicated that DBDPE may affect the locomotor regulatory network via different mechanisms at lower and higher concentrations. On the one hand, embryonic exposure to 2.91 µg/L DBDPE transiently promoted spontaneous coiling contractions, but showed no effects on touch-response and swimming activity in zebrafish larvae. The whole-body contents of neurotransmitters were significantly decreased. Significant decreased protein abundances of α1-TUBULIN and SYN2a and molecular docking results pointed out possible interactions of DBDPE with these two proteins. However, these changes may be unconcerned with the transient hyperactivity, and the exact molecular mechanisms need further investigation. On the other hand, 29.14 and 97.12 µg/L DBDPE exposure caused longer-lasting effects in promoting spontaneous coiling contractions, and also touch-response and swimming activity. At the same time, increased ACh contents (without changes of other neurotransmitters) and ChAT activity and inhibited transcription of nAChRs were observed at higher concentrations. Molecular docking indicated direct interaction of DBDPE with ChAT. The results suggested that DBDPE induced hyperactivity at higher concentrations was probably involved with disrupted cholinergic system, with ChAT as a potential target. Given that the body burden of DBDPE in lower concentration group was comparable with those detected in wild fish, the current results may provide useful information for ecological risk assessment.


Assuntos
Retardadores de Chama , Peixe-Zebra , Animais , Bromobenzenos , Colinérgicos/metabolismo , Colinérgicos/farmacologia , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Larva , Simulação de Acoplamento Molecular , Neurotransmissores/metabolismo , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacologia , Peixe-Zebra/metabolismo
12.
Environ Pollut ; 312: 120067, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36067974

RESUMO

According to fire accident statistics, fires in buildings are increasing. The flame-retardant performance of insulation materials is considered an important factor for preventing the spread of fire and ensuring evacuation. This study evaluated the flame-retardant performance and combustion characteristics of four types of organic thermal insulation used as core materials in sandwich panels. The flame-retardant performance evaluation based on total heat release and heat release rate revealed that phenolic foam (PF) satisfied the criteria for non-combustible grade insulation. An analysis of the hazardous gases released while combustion of the four insulation materials indicated that a significant amount of CO was released-an average of 19,000 ppm or higher-in the rigid urethan foam (PIR) and spray-type polyurethane foam (SPU). The fractional effective dose (FED) value was derived from the gas analysis results according to ISO 13344. PIR and SPU had an average FED value of 2.0 or higher and were identified as very dangerous in the case of fire accidents. Moreover, the evacuation time in the case of a fire in a warehouse-type building was comprehensively analyzed considering the material, size, and height for the four types of insulation. PIR was the most vulnerable to fire, and for PF, the danger limit was not reached until the end of the simulation.


Assuntos
Incêndios , Retardadores de Chama , Aerossóis , Retardadores de Chama/toxicidade , Gases
13.
Chemosphere ; 308(Pt 3): 136486, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36150222

RESUMO

Decabromodiphenyl ether (mainly BDE-209) is a commonly used brominated flame retardant in various industrial products. Although its damage to the reproduction system has been established, its effect on erectile function remains unclear. The present study investigated whether BDE-209 induced erectile dysfunction in male SD rats and the underlying mechanisms. Pubertal male rats were exposed to BDE-209 orally (0, 5, 50, and 500 mg/kg/day) for 28 days and the ICP (intracavernous pressure) and MAP (mean arterial pressure) were measured. After the rats were euthanized, the fibrosis and apoptosis levels were evaluated. Additionally, the endothelial function of the rat vascular endothelium cells and the human umbilical vein endothelial cells were impaired after treatment with 50 µM and 100 µM BDE-209. Moreover, the bioinformatics based on CTD database and ChIP-X Enrichment Analysis, version 3 (ChEA3) and molecular docking analysis demonstrated that 5 transcription factors (NFKB1, NR3C1, E2F5, REL, IRF4) might regulate endothelial function by affecting the expression of interactive genes (BCL-2, CAP3, CAT, TNF, MAPK1, and MAPK3). In summary, the present study demonstrated that BDE-209 might affect downstream interactive genes by binding to transcription factors, leading to corpus cavernosum endothelial dysfunction, thus contributing to erectile dysfunction in rats.


Assuntos
Disfunção Erétil , Retardadores de Chama , Animais , Células Endoteliais/metabolismo , Disfunção Erétil/metabolismo , Disfunção Erétil/terapia , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados , Humanos , Masculino , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição
14.
Anal Biochem ; 657: 114887, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36150471

RESUMO

Bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is an extensively used novel brominated flame retardant that is present ubiquitously in the environment and in biota. However, there is inadequate data on its potential hepatotoxicity to humans. In this study, high-coverage quantitative metabolomics based on 12C-/13C-dansylation labeling LC-MS was performed for the first time to assess the metabolic perturbations and underlying mechanisms of TBPH on human hepatocytes. HepG2 cells were exposed to TBPH at dosages of 0.1,1,10 µM for 24 or 72 h. Overall, 1887 and 1364 amine/phenol-containing metabolites were relatively quantified in cells and culture supernatant. Our results revealed that exposure to 0.1 µM TBPH showed little adverse effects, whereas exposure to 10 µM TBPH for 24 h enhanced intracellular protein catabolism and disrupted energy and lipid homeostasis-related pathways such as histidine metabolism, pantothenate and CoA biosynthesis, alanine, aspartate and glutamate metabolism. Nevertheless, most of these perturbations returned to the same levels as controls after 72 h of exposure. Additionally, prolonged TBPH exposure increased oxidative stress, as reflected by marked disturbances in taurine metabolism. This study sensitively revealed the dysregulations of intracellular and extracellular metabolome induced by TBPH, providing a comprehensive understanding of metabolic responses of cells to novel brominated flame retardants.


Assuntos
Retardadores de Chama , Ácidos Ftálicos , Alanina , Aminas , Ácido Aspártico , Coenzima A , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Glutamatos , Hepatócitos/metabolismo , Histidina , Humanos , Lipídeos , Metabolômica , Fenóis , Taurina
15.
Ecotoxicol Environ Saf ; 241: 113778, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36068737

RESUMO

Organophosphate flame retardants (OPFRs) are alternatives to brominated flame retardants (BFRs) and have recently gained wide acceptance in various materials. For the treatment and prevention of diseases, it is also important to clarify the relationship between OPFRs and tumors, despite the fact that OPFRs are less toxic than BFRs. This research used the TCGA and CTD databases for transcriptome profiling and identifying OPFRs-related genes. GO and KEGG analyses suggested that OPFRs may be closely related to colorectal cancer (CRC), and genes correlated with OPFRs were significantly and differently expressed between tumor and normal group. Further, OPFRs-related genes were associated with a good prognosis in CRC patients. The deeper research demonstrated that one of the OPFRs-triphenyl phosphate could significantly increased the viability and proliferation of CRC cell lines compared with the control group. In addition, Our research also found that melatonin at 50 µM could significantly impact CRC cell proliferation and migration ability induced by TPP.


Assuntos
Neoplasias Colorretais , Retardadores de Chama , Linhagem Celular , Neoplasias Colorretais/genética , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Humanos , Organofosfatos/metabolismo , Organofosfatos/toxicidade , Compostos Organofosforados/toxicidade
16.
Ecotoxicol Environ Saf ; 241: 113813, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36068742

RESUMO

The potential accumulation of chlorinated organophosphorus flame retardants (Cl-OPFRs) in aquatic environments sparked interest in studying the effects of Cl-OPFRs on cyanobacterial blooms. In this work, two common Cl-OPFRs, tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tris(2-chloroethyl) phosphate (TCEP), induced dose-dependent biphasic effect on bloom-forming M. aeruginosa. The hormetic response to low-dose Cl-OPFRs was associated with the upregulation of the type I NADH dehydrogenase (NDH-1) complex and its mediated cyclic electron transfer (CET) pathway, as reflected by a transient post-illumination increase in chlorophyll fluorescence, the dark reduction of P700+ and the change of NDH-1-related gene expression. The increased CET activity and carotenoid content jointly reduced the intracellular ROS production, facilitating cyanobacterial growth. Conversely, a higher concentration of both Cl-OPFRs induced severe inhibition of growth and photosynthetic oxygen-evolving activity through an imbalance between PSII and PSI. Toxic-dose Cl-OPFRs inhibited state transition and fixed cells into the State I with a higher PSII/PSI ratio, as indicated by chlorophyll fluorescence induction, 77 K fluorescence emission spectra and photosystem stoichiometry. The elevated PSII/PSI ratio created an imbalance between the two photosystems and eventually lead to ROS overproduction, which generate adverse effects on cell growth. This work provides important insights into the hormetic mechanism of Cl-OPFRs on Microcystis aeruginosa and their potential roles in harmful cyanobacteria blooms.


Assuntos
Retardadores de Chama , Microcystis , Clorofila , Retardadores de Chama/toxicidade , Organofosfatos , Compostos Organofosforados/toxicidade , Fosfatos , Espécies Reativas de Oxigênio
17.
Molecules ; 27(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36144785

RESUMO

BACKGROUND: Tetrabromobisphenol A (TBBPA) is the most commonly used brominated flame retardant (BFR) in the industry. TBBPA has been determined in environmental samples, food, tap water, dust as well as outdoor and indoor air and in the human body. Studies have also shown the toxic potential of this substance. In search of a better and less toxic BFR, tetrabromobisphenol S (TBBPS) has been developed in order to replace TBBPA in the industry. There is a lack of data on the toxic effects of TBBPS, while no study has explored apoptotic mechanism of action of TBBPA and TBBPS in human leukocytes. METHODS: The cells were separated from leucocyte-platelet buffy coat and were incubated with studied compounds in concentrations ranging from 0.01 to 50 µg/mL for 24 h. In order to explore the apoptotic mechanism of action of tested BFRs, phosphatidylserine externalization at cellular membrane (the number of apoptotic cells), cytosolic calcium ion and transmembrane mitochondrial potential levels, caspase-8, -9 and -3 activation, as well as PARP-1 cleavage, DNA fragmentation and chromatin condensation in PBMCs were determined. RESULTS: TBBPA and TBBPS triggered apoptosis in human PBMCs as they changed all tested parameters in the incubated cells. It was also observed that the mitochondrial pathway was mainly involved in the apoptotic action of studied compounds. CONCLUSIONS: It was found that TBBPS, and more strongly TBBPA, triggered apoptosis in human PBMCs. Generally, the mitochondrial pathway was involved in the apoptotic action of tested compounds; nevertheless, TBBPS more strongly than TBBPA caused intrinsic pathway activation.


Assuntos
Retardadores de Chama , Bifenil Polibromatos , Cálcio , Caspase 8 , Cromatina , Retardadores de Chama/análise , Retardadores de Chama/toxicidade , Humanos , Leucócitos Mononucleares/química , Fosfatidilserinas , Inibidores de Poli(ADP-Ribose) Polimerases , Bifenil Polibromatos/análise , Bifenil Polibromatos/toxicidade
18.
Artigo em Inglês | MEDLINE | ID: mdl-36113845

RESUMO

Tetrabromobisphenol A bis (2-hydroxyethyl ether) (TBBPA-DHEE) is a derivative of Tetrabromobisphenol A (TBBPA) used as an intermediate flame retardant in engineering polymers. The mechanism of neurodevelopmental toxicity of TBBPA-DHEE remains unclear due to limited toxicological data. We performed behavioral and transcriptomic analyses to assess the neurodevelopmental effects of TBBPA-DHEE on developing zebrafish and potential toxicity mechanisms. Our result shows that exposure to TBBPA-DHEE significantly increased mortality, deformity rate, and reduction in hatch rate, hatchability, and body length relative to the DMSO control. The behavior analysis indicates that TBBPA-DHEE significantly reduced the spontaneous movement of larva compared to the control. The TSH and GH levels were significantly reduced in all the exposure groups in a concentration-dependent manner relative to the DMSO control. TBBPA-DHEE exhibited a significant reduction in locomotor activity across all the exposure groups in the light/dark locomotion test. The transcriptomic analysis result shows that 579 genes were differentially expressed. KEGG analysis shows the enrichment of complement cascade, JAK-STAT signaling pathway, cytokine-cytokine interaction, and phototransduction pathway resulting in a change in mRNA expression of their genes. These observed changes in developmental endpoints, hormonal level, and alteration in mRNA expression of component genes involved in neurodevelopmental pathways could be part of the possible mechanism of the observed toxic effects of TBBPA-DHEE exposure on zebrafish. This study could reveal the possible neurodevelopmental toxicity of TBBPA-DHEE to aquatic species, which could help uncover the health implications of emerging environmental contaminants.


Assuntos
Retardadores de Chama , Bifenil Polibromatos , Poluentes Químicos da Água , Animais , Citocinas/metabolismo , Dimetil Sulfóxido/metabolismo , Éter/metabolismo , Éteres/análise , Éteres/metabolismo , Retardadores de Chama/toxicidade , Bifenil Polibromatos/análise , Bifenil Polibromatos/metabolismo , Bifenil Polibromatos/toxicidade , Polímeros , RNA Mensageiro/metabolismo , Tireotropina/genética , Tireotropina/metabolismo , Transcriptoma , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
19.
Environ Res ; 215(Pt 1): 114268, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36075477

RESUMO

Several halogenated flame retardants (HFRs) have been identified as thyroid disruptors in birds including the polybrominated diphenyl ether (PBDE) mixtures, which have been replaced with other HFRs such as Dechlorane-604 (Dec-604). Dec-604 Component B (Dec-604 CB), a putative debrominated product of Dec-604, has been frequently reported in urban-adapted ring-billed gulls (Larus delawarensis) breeding in the Montreal area (QC, Canada). The metabolic pathways of Dec-604 are yet to be characterized, although the occurrence of Dec-604 CB in gulls may suggest that enzyme-mediated dehalogenation may occur, potentially involving the thyroid deiodinases. The objective of this study was to investigate the effect of Dec-604 on type 1 deiodinase (DIO1) in the presence of thyroxine (T4) in an in vitro DIO1 assay using liver microsomes of ring-billed gulls that are highly exposed to HFRs in the Montreal area, and to determine whether DIO1 is involved in the in vitro debromination of Dec-604. We tested the in vitro activity of DIO1 in gull liver microsomes in the presence of five concentrations of Dec-604 ranging from 0.86 to 86.21 nM. HFR concentrations (Σ40HFR) were also determined in liver samples of gulls. Results showed that total DIO1 activity in gull liver microsomes was increased by three of the five concentrations of Dec-604. No relationship between liver Σ40HFR concentrations and DIO1 activity was observed, except for T2 formation rates that significantly decreased with increasing liver HFR concentrations. Moreover, greater Dec-604 CB to Dec-604 concentration ratios in activated gull microsomes (with the DIO1 cofactor dithiothreitol) were found at the intermediate Dec-604 concentration compared to controls. These results suggested that liver microsome DIO1 activity may be perturbed in ring-billed gulls exposed to Dec-604, and be involved at least in part, in the debromination of Dec-604 leading to the formation of Dec-604 CB.


Assuntos
Charadriiformes , Retardadores de Chama , Febre Hemorrágica com Síndrome Renal , Animais , Biotransformação , Charadriiformes/metabolismo , Ditiotreitol/metabolismo , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/metabolismo , Éteres Difenil Halogenados/toxicidade , Iodeto Peroxidase/metabolismo , Glândula Tireoide , Tiroxina/metabolismo
20.
Neurotoxicol Teratol ; 93: 107118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35934274

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been worldwide used as flame retardants. Among them, decabromodiphenyl ether (BDE-209) is the most applied and becomes ubiquitous in the environment and organisms. It can alter spontaneous behavior and affect the cholinergic system in rodents. Ultrasonic vocalizations (USVs) emitted by rat pups during isolation are widely employed as neurobehavioral indexes, and the cholinergic system supports their normal expression. However, whether BDE-209 can alter isolation USVs were unknown. In this study, BDE-209 was daily administered to mothers at 0, 500, or 1000 mg/kg b.w. from gestational day (GD) 15 to postnatal day (PND) 21. On PNDs 7, 10, 13, and 16, rat pups were individually isolated from mothers, and their USVs were recorded for 5 min after 5-min habituation and then analyzed. The results indicated that BDE-209 exposure can cause acoustic alterations in isolation USVs. The high-dose pups emitted USVs with shorter duration than the control pups did. Moreover, the percentages of frequency-modulated (FM) USVs in the high-dose pups were lower than those in the control pups. The mechanisms to alter acoustic characteristics of isolation USVs need further investigation. USV analysis is a useful method that provides neurobehavioral evidence.


Assuntos
Retardadores de Chama , Éteres Difenil Halogenados , Animais , Colinérgicos/farmacologia , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Ratos , Ultrassom , Vocalização Animal
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...