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1.
Adv Exp Med Biol ; 1121: 21-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31392649

RESUMO

The increasing prevalence of non communicable diseases (NCDs) poses main challenges to global public health. Various environmental exposures to different chemicals and pollutants might interact with genetic and epigenetic mechanisms resulting in the development of NCDs. Among these environmental exposures, endocrine disrupting chemicals (EDCs) consist of a group of compounds with potential adverse health effects and the interference with the endocrine system. They are mostly used in food constituents, packaging industries and pesticides. Growing number of in vitro, in vivo, and epidemiological studies documented the link of EDC exposure with obesity, diabetes, and metabolic syndrome, which are the underlying factors for development of NCDs. Prevention of exposure to EDCs and reduction of their production should be underscored in strategies for primordial prevention of NCDs.


Assuntos
Disruptores Endócrinos , Exposição Ambiental , Poluentes Ambientais , Doenças não Transmissíveis , Disruptores Endócrinos/toxicidade , Exposição Ambiental/prevenção & controle , Poluentes Ambientais/toxicidade , Humanos , Praguicidas/toxicidade
2.
Biomed Environ Sci ; 32(6): 406-418, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262386

RESUMO

OBJECTIVE: Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. METHODS: In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. RESULTS: The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. CONCLUSION: It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.


Assuntos
Autofagia/efeitos dos fármacos , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos Wistar , Fator de Transcrição STAT1/metabolismo , TYK2 Quinase/metabolismo
3.
Aquat Toxicol ; 214: 105232, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271907

RESUMO

Understanding the mode of action of the different pollutants in human and wildlife health is a key step in environmental risk assessment. The aim of this study was to determine signatures that could link morphological phenotypes to the toxicity mechanisms of four Endocrine Disrupting Chemicals (EDCs): bisphenol A (BPA), perfluorooctanesulfonate potassium salt (PFOS), tributyltin chloride (TBT), and 17-ß-estradiol (E2). Zebrafish (Danio rerio) eleutheroembryos were exposed from 2 to 5 dpf to a wide range of BPA, PFOS, TBT and E2 concentrations. At the end of the exposures several morphometric features were assessed. Common and non-specific effects on larvae pigmentation or swim bladder area were observed after exposures to all compounds. BPA specifically induced yolk sac malabsorption syndrome and altered craniofacial parameters, whereas PFOS had specific effects on the notochord formation presenting higher rates of scoliosis and kyphosis. The main effect of E2 was an increase in the body length of the exposed eleutheroembryos. In the case of TBT, main alterations on the morphological traits were related to developmental delays. When integrating all morphometrical parameters, BPA showed the highest rates of malformations in terms of equilethality, followed by PFOS and, distantly, by TBT and E2. In the case of BPA and PFOS, we were able to relate our results with effects on the transcriptome and metabolome, previously reported. We propose that methodized morphometric analyses in zebrafish embryo model can be used as an inexpensive and easy screening tool to predict modes of action of a wide-range number of contaminants.


Assuntos
Embrião não Mamífero/anatomia & histologia , Embrião não Mamífero/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/embriologia , Ácidos Alcanossulfônicos/toxicidade , Animais , Compostos Benzidrílicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/farmacologia , Estradiol/toxicidade , Fluorcarbonetos/toxicidade , Humanos , Larva/efeitos dos fármacos , Análise dos Mínimos Quadrados , Análise Multivariada , Fenóis/toxicidade , Análise de Componente Principal , Análise de Sobrevida , Testes de Toxicidade , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade
4.
Environ Pollut ; 253: 29-38, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302400

RESUMO

Over 80,000 endocrine-disrupting chemicals (EDCs) are considered emerging contaminants (ECs), which are of great concern due to their effects on human health. Quantitative structure-activity relationship (QSAR) models are a promising alternative to in vitro methods to predict the toxicological effects of chemicals on human health. In this study, we assessed a deep-learning based QSAR (DL-QSAR) model to predict the qualitative and the quantitative effects of EDCs on the human endocrine system, and especially sex-hormone binding globulin (SHBG) and estrogen receptor (ER). Statistical analyses of the qualitative responses indicated that the accuracies of all three DL-QSAR methods were above 90%, and greater than the other statistical and machine learning models, indicating excellent classification performance. The quantitative analyses, as assessed using deep-neural-network-based QSAR (DNN-QSAR), resulted in a coefficient of determination (R2) of 0.80 and predictive square correlation coefficient (Q2) of 0.86, which implied satisfactory goodness of fit and predictive ability. Thus, DNN was able to transform sparse molecular descriptors into higher dimensional spaces, and was superior for assessment qualitative responses. Moreover, DNN-QSAR demonstrated excellent performance in the discipline of computational chemistry by handling multicollinearity and overfitting problems.


Assuntos
Aprendizado Profundo , Ecotoxicologia , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Relação Quantitativa Estrutura-Atividade , Biologia Computacional , Disruptores Endócrinos/metabolismo , Poluentes Ambientais/metabolismo , Humanos , Redes Neurais (Computação) , Receptores Estrogênicos/metabolismo , Globulina de Ligação a Hormônio Sexual
5.
Aquat Toxicol ; 214: 105240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319295

RESUMO

Fish has a strong resistance to microcystins (MCs), cyclic heptapeptide cyanotoxins, known as endocrine disrupting chemicals (EDCs) which are released during cyanobacterial blooms and many laboratory and field studies have found the hepatic recovery of fish from the MCs exposure. The aim of the present study was to investigate the recovery mechanisms of reproductive function of adult zebrafish (Danio rerio) from microcystin-LR (MC-LR) exposure. Therefore, adult female zebrafish were exposed to 0, 1 or 50 µg/L of MC-LR for 21days and transferred to MC free water for another 21 days to investigate the recovery. After MC-LR exposure, marked histological lesions in the gonads, decreased the percentage of mature oocytes, decreased number of spawned eggs, decreased fertilization and hatching rates were observed. MC-LR exposure increased the concentration of 17ß-estradiol (E2), testosterone (T) and vitellogenin (VTG) in female zebrafish. Some gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis significantly changed. The protein levels of 17ßhsd and cyp19a remarkably increased in the MC-LR exposure groups. However, our laboratory observation also indicates that zebrafish transferred from microcystin exposure to toxin-free water and reared for 21 days exhibited a nearly complete recovery of reproductive functions, including histological structure, increased the percentage of matured oocytes and spawned eggs, stable hormone levels, well-balanced transcriptional and translational levels. These results indicate that after MC-LR exposure, the reproductive impairments in zebrafish are also reversible likewise hepatic recovery seen by different studies in fish. Future studies should be conducted to explore a better understanding of the recovery mechanisms of fish from microcystins exposure.


Assuntos
Exposição Ambiental , Microcistinas/toxicidade , Reprodução/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Disruptores Endócrinos/toxicidade , Feminino , Hormônios/sangue , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ovário/citologia , Ovário/efeitos dos fármacos , Ovário/fisiologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/sangue , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
6.
Bull Environ Contam Toxicol ; 103(3): 400-404, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352602

RESUMO

This study aimed to investigate the impact of estrogenic endocrine disruptors in adult male Nile Tilapia (Oreochromis niloticus) from the Seven Lakes (Bunot, Calibato, Mohicap, Palakpakin, Pandin, Sampaloc and Yambo) of San Pablo City in Laguna, Philippines. Fish were collected from aquaculture operations in each lake from July to September 2017 and examined for plasma vitellogenin (VTG) levels, hepatosomatic index (HSI) and gonadosomatic index (GSI). In comparison to the reference group (Pandin Lake), fish from Mohicap, Sampaloc and Yambo had higher levels of plasma VTG. HSI was increased in fish from Bunot Lake while it was markedly reduced in fish from Sampaloc Lake. Comparable GSI were obtained in all samples. While most examined fish are in active spermatogenesis, fish from Sampaloc Lake had immature gonads with no spermatozoa, and with minimal to moderate Leydig cell vacuolation and hyperplasia. The results suggest that cultured Nile tilapia from Sampaloc Lake is most adversely affected by endocrine-active compounds. The identification and quantification of these chemicals are recommended in future studies.


Assuntos
Ciclídeos/fisiologia , Estrogênios/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Aquicultura , Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Estrogênios/análise , Gônadas/efeitos dos fármacos , Lagos/química , Masculino , Filipinas , Inquéritos e Questionários , Vitelogeninas/sangue , Poluentes Químicos da Água/análise
7.
Ecotoxicol Environ Saf ; 182: 109389, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31272027

RESUMO

Simvastatin (SV), as an hypocholesterolaemic drug, has been detected in various aquatic environment. However, limited information is available on the effects of SV on freshwater invertebrates. In the present study, we investigated the toxic effects of SV on Daphnia. magna (D. magna) through measuring the physiological changes (e.g., survival, growth rate, and reproduction) in a 21-d chronic toxicity test We also determined the expression of seven detoxification and reproduction-related genes (i.e. HR96, P-gp, CYP360A8, GST, CYP314, EcR and Vtg) and several enzymes (i.e. APND, ERND, GST and CAT) in a acute test (24 h). Results showed that high concentration (e.g. 50 µg L-1) of SV for short time exposure (e.g. 24 h) significantly induced the expression of HR96 and P-gp (e.g. up to 2.5 folds)and enzymes (e.g. increasing 4.0 folds for ERND and GST activity) in D. magna.. The long-term chronic exposure (21 days) may cause the changes of life history parameters such as decreasing total egg production number per individual and intrinsic growth rates etc. SV may act as a potential endocrine disruptor to D. magna and the reproduction parameters were more sensitive endpoints than the survival and growth for evaluating SV exposure.


Assuntos
Daphnia , Disruptores Endócrinos/toxicidade , Sinvastatina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Daphnia/efeitos dos fármacos , Daphnia/enzimologia , Daphnia/genética , Inativação Metabólica/efeitos dos fármacos , Inativação Metabólica/genética , Reprodução/efeitos dos fármacos , Reprodução/genética , Testes de Toxicidade Crônica
8.
Environ Pollut ; 249: 1049-1059, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146311

RESUMO

Tebuconazole is a widely used fungicide that has been detected in water ecosystems, of which the concentrations may affect the endocrine function of aquatic organisms. At present study, tissue-specific bioaccumulation of tebuconazole was found in ovary of adult zebrafish, indicating a potential risk of endocrine disruption. In order to evaluate the potential endocrine disrupting effects, three life stages (2 hpf (hours post-fertilization) -60 dpf (days post-fertilization), Stage I; 60-120 dpf, Stage II; 180-208 dpf, Stage III) of zebrafish (Danio rerio) were chronically exposed to tebuconazole at the concentrations ranging from 0.05 mg/L to 1.84 mg/L. Result showed that exposed to tebuconazole could lead to a male-biased sex differentiation in juvenile zebrafish and significant decrease of the percentage of germ cells in sexually-mature zebrafish. Egg production was significantly inhibited by 57.8% and 19.2% after Stage II- and Stage III-exposures, respectively. The contents of 17ß-estradiol in gonad decreased by 63.5% when exposed to 0.20 mg/L tebuconazole at Stage II and by 49.5% after exposed to 0.18 mg/L tebuconazole at Stage III, respectively. For all stages exposure, reductions in 17ß-estradiol/testosterone ratio were observed, indicating an imbalance in steroids synthesis. Additionally, tebuconazole reduced the expression of cyp19a, which was consistent with the decrease of E2 level. In overall, the present findings indicated that, playing as an anti-estrogen-like chemical, tebuconazole inhibited the expression of Cyp19, thereby impairing steroid hormones biosynthesis, leading to a diminished fecundity of zebrafish.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Gônadas/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Animais , Aromatase/metabolismo , Embrião não Mamífero/metabolismo , Disruptores Endócrinos/metabolismo , Feminino , Fungicidas Industriais/metabolismo , Gônadas/embriologia , Diferenciação Sexual/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Triazóis/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismo
9.
Ecotoxicol Environ Saf ; 181: 419-427, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31220782

RESUMO

Nonylphenol (NP) and its detrimental effects on the environment, humans, wildlife, fish and birds is an increasingly important global research focus. The number of investigations on the toxicity and metabolic fate of NP in plants is however limited. This paper reviews the prevalence and source of NP in plants and the effect it has on its morphological, physiological and ultrastructural status. Fruit and vegetables have been found to contain levels of NP that is twenty-fold exceeding the no observable effect level (NOEL) of freshwater algae. Apart from the potential risk this poses to the health of consumers, it can overburden the plant's natural defence system, leading to growth disorders. Plants exposed to NP show signs of overall growth reduction, changes in organelle structure and oxidative damage. These adverse effects may exacerbate the food security dilemma faced by many countries and impede their progress towards attaining the sustainable development goals.


Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Fenóis/toxicidade , Plantas/efeitos dos fármacos , Animais , Disruptores Endócrinos/análise , Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Frutas/química , Frutas/crescimento & desenvolvimento , Humanos , Fenóis/análise , Desenvolvimento Vegetal/efeitos dos fármacos , Plantas/anatomia & histologia , Plantas/metabolismo , Verduras/química , Verduras/crescimento & desenvolvimento
10.
Environ Sci Pollut Res Int ; 26(23): 23491-23504, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201698

RESUMO

This study was conducted to investigate the effects of maternal exposure to bisphenol A (BPA) on testis development of F1 male mice. The BPA exposure model of pregnant mice was prepared by intragastric administration of BPA at the doses of 0, 2.5, 5, 10, 20, and 40 mg/kg/day at gestation day (GD) 0.5-17.5. The testis index of the offspring mice was calculated at postnatal day (PND) 21 and PND 56. The results showed that maternal exposure to 20 mg/kg BPA during pregnancy significantly increased the testicular index of F1 males at PND 21, and 40 mg/kg BPA significantly decreased the testicular index of F1 males at PND 56 (P < 0.01). BPA significantly reduced serum testosterone (T) and estradiol (E2) levels, and improved testicular ERα and ERß levels in F1 males at both PND 21 and PND 56. BPA exposure also upregulated transcription of testicular Dnmt1 and inhibited the transcription of testicular Dnmt3A and Dnmt3B in F1 mice at PND 21. BPA reduced the transcriptional level of testicular DNA methyltransferase (Dnmt), increased the expression of testicular caspase-7, caspase-9, and bax, and decreased the expression of bcl-2 in F1 mice at PND 56. Consistent with that, BPA improved the apoptosis rate in the testis at PND 56 (P < 0.01 or P < 0.05). Our study indicates that BPA disrupts the secretion of testosterone, estradiol, and estrogen receptors by interfering with the transcription of testicular DNA methyltransferase (Dnmt) in offspring males, which damages testicular tissues and affects the potential reproductive function.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Testículo/crescimento & desenvolvimento , Animais , DNA (Citosina-5-)-Metiltransferases , Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Masculino , Exposição Materna , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Proteínas Proto-Oncogênicas c-bcl-2 , Receptores Estrogênicos/metabolismo , Diferenciação Sexual , Testículo/efeitos dos fármacos , Testosterona/sangue , Testes de Toxicidade
11.
Environ Sci Process Impacts ; 21(7): 1099-1114, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31179481

RESUMO

Endocrine active contaminants (EACs) in environmental samples can pose a range of toxicological threats to ecosystems, especially through their impacts on reproductive pathways mediated by the estrogen receptor. The physicochemical properties of known organic EACs vary greatly and typically require different sample preparation techniques to identify different classes of compounds. EAC sources are similarly diverse, including both endogenous compounds and anthropogenic chemicals found in personal care products, pharmaceuticals, and their transformation products, which are often disposed of to sewers at their end of use. Looking for EACs in sewage sludge proposes a bottom-up, or end-of-use and treatment approach to discover environmentally relevant EACs, since many EACs accumulate in sludges even after application of robust wastewater treatment processes. This study demonstrates an extraction and analytical method capable of detecting a broad spectrum of known and suspected EACs via High Resolution Liquid Chromatography Quadropole Time-of-Flight Mass Spectrometry (LC-QTOF-MS) suspect screening of fourteen California sewage sludge samples. Spike-recovery experiments were performed using twelve carefully selected surrogates to assess different extraction solvents, sample weights, extraction pH values, procedures for combining extracts with different extraction pH's, and solid phase extraction cartridges. Using LC-QTOF-MS, identifications of several other organic compounds in the samples were made, a goal unachievable with unit resolution mass spectrometry. Suspect screening of California sludge samples discovered 118 compounds including hormones, pharmaceuticals, phosphate flame retardants, recreational drugs, antimicrobials, and pesticides. Additionally, 22 of these identified compounds are predicted to interfere with estrogen receptors or other reproductive/developmental pathways based on the VEGA QSAR toxicity prediction model.


Assuntos
Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Modelos Teóricos , Esgotos/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , California , Cromatografia Líquida de Alta Pressão , Valor Preditivo dos Testes , Relação Quantitativa Estrutura-Atividade , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Águas Residuárias/análise , Purificação da Água/métodos
12.
Food Chem Toxicol ; 131: 110552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31163220

RESUMO

[OBJECTIVE]: Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, may act as an endocrine disruptor and cause developmental toxicity. Differentiated human embryonic stem cells (hESCs) were used to investigate the underlying mechanism of the embryotoxicity induced by DEHP. [Materials and Methods] H9-hESCs were treated with DEHP at different concentrations for 10 days, and the cytotoxicity of DEHP on cell proliferation was determined using a cell-microelectronic sensing technique (Real-Time Cellular Analysis: RTCA). Based on the 50% inhibitory proliferation concentration (IC50), differentiated H9-hESCs were treated with DEHP at 0, 50, 100, and 200 µg/ml for 120 h, followed by measurement of its toxic effects on the transcriptome by mRNA microarray and QuantiGene Plex (QGP). Proteins were detected by the iTRAQ-based proteomics method and the proteins related to the PPARγ/PTEN/Akt pathways were measured by western blotting. The progression of the cell cycle and apoptosis were characterized using flow cytometry (FCM). In other experiments, hESCs were pre-treated with GW9662 (20 µM), a specific PPARγ inhibitor, for 30 min, followed by exposure to GW9662 (20 µM) and DEHP (200 µg/ml) for 120 h to observe the underlying mechanism of DEHP's embryotoxicity. [RESULTS]: DEHP inhibited H9-hESC cell proliferation in a dose-dependent manner, with an IC50 of 165.78 µg/ml. FCM results showed that DEHP could markedly induce cell cycle arrest and increase apoptosis. Gene microarray and QPG array analyses indicated that the peroxisome proliferator-activated receptor γ (PPARγ) was an apparent target for DEHP. We further demonstrated that DEHP could activate the PPARγ and upregulate the expression of PTEN downstream genes, and then play a negative role in the AKT signaling pathway. Cells pretreated with PPARγ inhibitor, GW9662, were shown to restore the effect of DEHP on the PPARγ/PTEN/AKT signaling pathway, and induce the recovery of cell cycle arrest and apoptosis. [CONCLUSION]: DEHP inhibited cell proliferation, promoted cell cycle arrest, and induced apoptosis through the PPARγ/PTEN/AKT signaling pathway in differentiated human embryonic stem cells. It suggested that DEHP exposure possibly cause reproductive or developmental toxicity in humans through the PPARγ signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Emulsões/síntese química , Emulsões/química , Humanos , PPAR gama/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Plastificantes/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Soroalbumina Bovina/química , Teratogênios/toxicidade
13.
Food Chem Toxicol ; 131: 110573, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31195070

RESUMO

This study was aimed at determining if oxidative stress imbalance in testes of rats occurs after n-butylparaben (n-ButP) exposure. Young male Sprague-Dawley rats were subcutaneously treated with n-ButP during one spermatogenic cycle (57 days) at 0 (control-oil), 150, 300 and 600 mg/kg/d with peanut oil as vehicle. A non-vehicle control group was also included. Antioxidant enzyme activities (superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase) and levels of reduced and oxidized glutathione were measured in testes. Lipid peroxidation and H2O2 concentrations were also assessed. Results showed an increase of oxidative stress in oil-treated groups, excepting 600 mg/kg/d, suggesting oxidative stress due to peanut oil. A possible antioxidant effect due to n-ButP and its metabolites was suggested at 600 mg/kg/d, the only group not showing oxidative stress. An increase of calcium concentration in testes was also observed. On the other hand, a physiologically-based pharmacokinetic (PBPK) model was developed and the concentrations of n-ButP and its metabolites were simulated in plasma and testes. The peak concentration (Cmax) in testes was found slightly higher than that in plasma. The current results indicate that peanut oil can cause oxidative stress while high doses of n-ButP can act as antioxidant agent in testes.


Assuntos
Disruptores Endócrinos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Parabenos/toxicidade , Testículo/efeitos dos fármacos , Animais , Antioxidantes/farmacocinética , Antioxidantes/toxicidade , Arachis/química , Biomarcadores/metabolismo , Cálcio/metabolismo , Catalase/metabolismo , Disruptores Endócrinos/farmacocinética , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Parabenos/farmacocinética , Óleo de Amendoim/toxicidade , Ratos Sprague-Dawley
14.
Food Chem Toxicol ; 131: 110554, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207305

RESUMO

The results of a large 2-year bisphenol A (BPA) rat study conducted by the NTP, called the CLARITY-BPA Core Study, were recently released. This study addressed some of the toxicological issues associated with BPA, including endocrine disruption and non-monotonic dose responses (NMDR). The study involved oral gavage treatment of rats to BPA at doses of 2.5-25,000 µg/kg-bw/day. To address NMDR, the 81 statistically significant findings (based on the primary statistical tests) from the Core Study were evaluated using a recently published methodology that relies upon six checkpoints to determine if there is evidence for a NMDR. Failure to meet the majority of the checkpoints indicates limited evidence of NMDR. The analysis found that only 2 of the 81 findings met at least 5 of the checkpoints: an increase in percent basophils in stop-dose females and decreased total bile acids in stop-dose males. However, these findings are not concordant or consistent with those of other BPA data. Importantly, none of the endocrine-related or reproductive endpoints fulfilled at least 5 of the checkpoints. This analysis found limited evidence for NMDR associated with BPA treatment in the study. These results are consistent with the conclusions reached in the Core Study report.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Animais , Basófilos/metabolismo , Ácidos e Sais Biliares/metabolismo , Relação Dose-Resposta a Droga , Feminino , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley
15.
Environ Pollut ; 246: 876-884, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159137

RESUMO

Ecotoxicological studies show the association between pesticide pollution and transgenerational toxicity in aquatic organisms. However, a less considered risk is that many pesticides can be metabolized and transferred to offspring as new toxicants. In this study, we used zebrafish to evaluate the maternal transfer risk of fipronil (FIP), which is a great threat to aquatic organisms with toxic metabolite formation. After 28-day exposure to environmentally relevant concentrations (1.0, 5.0 and 10.0 µg/L) of FIP in adult female zebrafish (F0), the toxicants off-loading and transgenerational toxicity in offspring were studied. High burdens of FIP and its sulfone metabolite were found in both F0 and the embryos (F1), resulting in increased CYP450 activity. The residual levels of the metabolite were higher than those of the parent compound. Chiral analysis further showed a preferential accumulation of S-enantiomer of FIP in both F0 and F1. Maternal exposure to FIP increased the malformation rate and decreased the swim speed in larvae. Additionally, after exposure, the levels of thyroid hormones (THs), including triiodothyronine (T3) and thyroxine (T4), decreased in both generations, particularly in the F1. Gene transcription expression along the hypothalamic-pituitary-thyroid (HPT) axis was also significantly affected. Maternal exposure to FIP increased sulfone metabolite enrichment and cause multiple toxic effects in F1. Findings from this study highlight the key role of biologically active product formation in the maternal transfer of pollutants and associated risk assessment.


Assuntos
Exposição Materna/efeitos adversos , Praguicidas/toxicidade , Pirazóis/toxicidade , Sulfonas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/toxicidade , Feminino , Praguicidas/metabolismo , Pirazóis/metabolismo , Sulfonas/metabolismo , Hormônios Tireóideos/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra
16.
Environ Pollut ; 246: 914-920, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159141

RESUMO

Pharmaceuticals and analogs of bisphenol A (BPA) are increasingly threatening environmental pollutants. In this study, mixtures of selected pharmaceuticals (diclofenac sodium salt, chloramphenicol, oxytetracycline hydrochloride, fluoxetine hydrochloride, estrone, ketoprofen, progesterone, gemfibrozil and androstenedione) were prepared with BPA and its two analogs (namely, bisphenols F and S) at such ratios to reflect environmentally detectable levels. Then, the mixture solutions were studied with a XenoScreen YES/YAS assay to determine the variations in the initial hormonal response of each pharmaceutical compound due to the presence of a bisphenol analog. The results obtained were modeled with the concentration addition (CA) and independent action (IA) approaches, the trueness of which was studied with model deviation ratios (MDR). The estrogenic agonistic activity of the drugs studied was most strongly affected by the presence of BPA in solution (twenty-one cases of synergy observed for CA models versus twelve cases of antagonism in the case of IA predictions). BPS shows a strong agonistic estrogenic impact on most of the drugs studied at medium and high concentration levels; androgenic agonistic activity was also impaired with elevated concentrations of BPS. Increasing the concentration of BPF in a reaction mixture also increased the number of YES + synergism incidences (for CA modeling). Estrone, progesterone and androstenedione were mostly affected by the highest BPF concentrations studied in the case of androgenic agonistic research performed.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Preparações Farmacêuticas/análise , Fenóis/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Androgênios/análise , Compostos Benzidrílicos/química , Bioensaio , Disruptores Endócrinos/química , Poluentes Ambientais/química , Estrogênios/análise , Fenóis/química , Testes de Toxicidade
17.
Sci Total Environ ; 687: 267-276, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31207516

RESUMO

The use of bisphenol A (BPA) in manufacturing of plastics is being gradually replaced by presumably safer analogues such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). Despite their widespread occurrence in the environment, there is a knowledge gap in their toxicological profiles. We investigated cytotoxic/genotoxic effects as well as changes in the expression of selected genes involved in the xenobiotic metabolism, response to oxidative stress and DNA damage upon exposure to BPs and their mixtures in human hepatocellular carcinoma HepG2 cells. BPS and BPF slightly decreased the viability of HepG2 cells, while BPAF was the most cytotoxic compound tested. BPA, BPF and BPAF induced the formation of DNA double strand breaks determined with γH2AX assay, while BPS was inactive (5-20 µg/mL). All four BPs up-regulated the expression of CYP1A1 and UGT1A1, while BPS up-regulated and BPAF down-regulated also the expression of GST1A. Only BPA up-regulated oxidative stress responsive gene GCLC, while BPAF up-regulated the expression of CDKN1A and GADD45a. At concentrations relevant for human exposure (ng/mL range) BPA and its analogues as individual compounds and in mixtures did not exert genotoxic activity, whereas BPA and BPAF as well as the mixtures up-regulated the expressions of CYP1A1 and UGT1A1.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Bioensaio , Dano ao DNA , Células Hep G2 , Humanos , Estresse Oxidativo , Sulfonas/toxicidade , Testes de Toxicidade
18.
Ecotoxicology ; 28(6): 643-649, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197615

RESUMO

Monogonont rotifers constitute, depending on the moment of the year, most of the zooplankton in many freshwater ecosystems. Sexual reproduction is essential in the development cycle of these organisms as it enables them to constitute stocks of cysts which can withstand adverse environmental conditions and hatch when favorable conditions return. However, endocrine disrupting compounds (EDCs) can interfere with the reproduction of organisms. The present work aimed to investigate the effects of cyproterone acetate (CPA, anti-androgen and progestogen synthetic steroid) at 0.5 mg L-1, on the sexual reproduction of Brachionus calyciflorus in a cross-mating experiment. Results show no impact on mixis whereas the fertilization rate and resting egg production were higher in females exposed to CPA (from embryogenesis to adult stage), regardless of the treatment applied to the males with which they were mating (i.e. males hatched from CPA-treated females or from control females). Moreover, neonate females which mothers has been exposed to 0.5 mg L-1 CPA had more oocytes in their germarium than control neonates. Our results suggest that the effects of CPA observed are not related to toxicity but rather are consistent with an endocrine disruption-related impact, probably through disturbance of the mate recognition protein (MRP) production and through interference with a steroid receptor. Moreover, the absence of effect on mixis rate indicates that mixis induction on the one hand and mating process and resting production on the other hand are not controlled by the same hormonal pathways.


Assuntos
Antagonistas de Androgênios/toxicidade , Acetato de Ciproterona/toxicidade , Disruptores Endócrinos/toxicidade , Rotíferos/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Reprodução/efeitos dos fármacos , Rotíferos/fisiologia , Zooplâncton/efeitos dos fármacos
19.
Environ Sci Pollut Res Int ; 26(23): 23328-23336, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197669

RESUMO

A wide range of endocrine disruptor compounds are routinely discharged to the ecosystem. Water contaminated with these compounds has a potential effect on the reproductive physiology of aquatic organisms as well as humans. In the present study, we tested the effect of the steroid estrogen, 17ß-estradiol, on Biomphalaria alexandrina, a snail species that is widely distributed in Egypt and that acts as an intermediate host for the human blood fluke, Schistosoma mansoni. The effects of exposure to 0.3 mg/L and 1 mg/L 17ß-estradiol on fecundity (MX) and reproductive rate (R0) of B. alexandrina were recorded. In addition, levels of steroid sex hormones and antioxidants in the hemolymph and ovotestis (OT) of exposed snails were measured. Histopathological changes in the OT of B. alexandrina were also investigated. Exposure to 0.3 mg/L and 1 mg/L 17ß-estradiol caused a significant increase in the number of egg masses per snail after 3 weeks and 1 week of exposure for the two tested concentrations compared with unexposed controls. An increase in the levels of progesterone hormone was recorded in the hemolymph of exposed snails in comparison with unexposed controls. Additionally, levels of the antioxidant enzyme glutathione (GSH) were increased in the hemolymph and OT tissues of snails after 2 and 4 weeks of exposure. Histopathological sections in the OT revealed an increase in the oocyte and a decrease in the sperm densities after 2 weeks and this effect was restored to normal conditions after 4 weeks of exposure to both tested concentrations. The current results indicate that B. alexandrina is sensitive to 17ß-estradiol and can therefore be used as bioindicator and model organism for the assessment of water pollution with endocrine disruptor compounds.


Assuntos
Biomphalaria/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Monitoramento Ambiental/métodos , Estradiol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Ecossistema , Egito , Biomarcadores Ambientais/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Gônadas/patologia , Hemolinfa/efeitos dos fármacos , Hemolinfa/metabolismo , Humanos
20.
Environ Pollut ; 252(Pt A): 388-398, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158667

RESUMO

Dibutyl phthalate (DBP), one of the most widely used plasticizers, is a known environmental endocrine disruptor that impairs male and female fertility. In this study, oral administration of DBP was given to pregnant mice on 14.5 days post coitus (dpc) for 3 days; and additionally, DBP was added into the culture of 14.5 dpc fetal ovaries for 3 days. DBP exposure during gestation disturbed the progression of meiotic prophase I of mouse oocytes, specifically from the zygotene to pachytene stages. Meanwhile, the DBP-exposed pachytene oocytes showed increased homologous recombination sites and unrepaired DNA damage. Furthermore, DBP caused DNA damage by increasing oxidative stress, decreased the expression of multiple critical meiotic regulators, and consequently induced oocyte apoptosis. Moreover, the effect of DBP on meiosis I prophase involved estrogen receptors α and ß. Collectively, these results demonstrated a set of meiotic defects in DBP-exposed fetal oocytes. As aberrations in homologous recombination can result in aneuploid gametes and embryos, this study provides new support for the deleterious effects of phthalates.


Assuntos
Dibutilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Recombinação Homóloga/efeitos dos fármacos , Prófase Meiótica I/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Plastificantes/toxicidade , Aneuploidia , Animais , Apoptose/efeitos dos fármacos , Feminino , Masculino , Prófase Meiótica I/genética , Camundongos , Oócitos/patologia , Ovário/efeitos dos fármacos , Ovário/patologia , Gravidez
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