Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.953
Filtrar
1.
Ecotoxicol Environ Saf ; 203: 111053, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888615

RESUMO

Vinclozolin is a common dicarboximide fungicide used to protect crops from diseases. It is also an endocrine disruptor and is thought to be related to abnormalities of the reproductive tract. However, its mechanism of inducing abnormalities of the male reproductive tract is still unclear. The purpose of this study was to study the effect of gestational vinclozolin exposure on the development of rat fetal Leydig cells. Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by gavage from gestational day 14-21. Vinclozolin dose-dependently reduced serum testosterone levels at doses of 50 and 100 mg/kg and the anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blotting showed that vinclozolin down-regulated the expression of Nr5a1, Sox9, Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3, Amh, Pdgfa, and Dhh and their encoded proteins. Vinclozolin reduced the number of NR2F2-positive stem Leydig cells at a dose of 100 mg/kg and enhanced autophagy in the testes. In conclusion, vinclozolin disrupts reproductive tract development and testis development in male fetal rats via several pathways.


Assuntos
Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Organogênese/efeitos dos fármacos , Oxazóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Testículo/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Testículo/embriologia , Testículo/patologia , Testosterona/sangue
2.
J Environ Pathol Toxicol Oncol ; 39(3): 201-212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865912

RESUMO

Acute and chronic effects of ultraviolet radiation (UVR) on human health have long been a concern. It is well known that acute UVR causes epidermal hyperplasia, erythema, delayed tanning, pigment darkening, and free-radical formation. Apart from acute effects of UVR, its chronic effects involve immunosuppression, photoaging, exacerbation, photodermatoses, and photocarcinogenesis. To protect skin from harmful effects of UVR, UV filters were developed. But these may cause harmful effects in humans and on the environment; adverse effects of these chemicals have been evaluated for > 20 yr. Studies show that UV filters may lead to endocrine disruption, hepatotoxicity, mutagenicity, and systemic toxicity. Literature on environmental effects of UV filters suggests that they are bioaccumulative, pseudopersistent, and possibly toxic to aquatic ecosystems. The objective of this review is to summarize toxic effects and safety concerns of organic UV filters on human beings and the environment. We focus on UV filters' organic endocrine-disrupting effects by reviewing both in vivo and in vitro studies.


Assuntos
Disruptores Endócrinos/toxicidade , Compostos Orgânicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Protetores Solares/toxicidade , Animais , Biotransformação , Disruptores Endócrinos/química , Disruptores Endócrinos/farmacocinética , Humanos , Estrutura Molecular , Compostos Orgânicos/química , Compostos Orgânicos/farmacocinética , Protetores Solares/química , Protetores Solares/farmacocinética
3.
Ecotoxicol Environ Saf ; 205: 111312, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956863

RESUMO

Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 µM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 µM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 µM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and ß-Catenin expression diminishing their membrane location. Furthermore, 50 µM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 µM CPF increase MMP2 gelatinolytic activity and expression, decrease ß-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.


Assuntos
Movimento Celular/efeitos dos fármacos , Clorpirifos/toxicidade , Disruptores Endócrinos/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteína Tirosina Quinase CSK/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Relação Dose-Resposta a Droga , Transição Epitelial-Mesenquimal/genética , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Células MCF-7 , Metaloproteinase 2 da Matriz/genética , Transdução de Sinais
4.
Aquat Toxicol ; 227: 105608, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32858424

RESUMO

As a feed additive in agriculture, the antibiotic oxytetracycline (OTC) has become widely distributed in the natural environment, leading to the exposure of many organisms to low doses of OTC. Although OTC is clinically contraindicated in children because of its multiple side effects, the effect of exposure to low doses of environmental OTC on children is unknown, particularly during development. In this study, we investigated the effects of OTC on the thyroid endocrine system in zebrafish, through determinations of the whole-body contents of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) by enzyme-linked immunosorbent assay, and analysis of the mRNA expression of regulatory genes involved in the hypothalamus-pituitary-thyroid (HPT) axis using quantitative real-time polymerase chain reaction. Zebrafish embryos were exposed to OTC at environmentally relevant concentrations from 2 h to 120 days post-fertilisation. After exposure to OTC at 1,000 and 5,000 ng/L, T3 contents were significantly enhanced (37.8% and 45.1%, respectively) and TSH contents were reduced (16% and 16.3%, respectively) compared with those in the controls. The OTC-driven increase in the transcription of genes involved in thyroid synthesis (tpo and nis) may be responsible for the altered T3 levels. These data indicate that OTC may cause thyroid dysfunction and lead to reduced TSH secretion owing to enhanced negative feedback control of the HPT axis. Meanwhile, a decrease in body length, weight, and BMI and an increase in heart rate were observed with increasing OTC exposure. In conclusion, our results indicate that long-term exposure to low concentrations of OTC may alter the transcription of key genes involved in the HPT axis, as well as T3 and TSH contents, thereby disrupting the thyroid system and affecting the growth and development of zebrafish.


Assuntos
Oxitetraciclina/toxicidade , Glândula Tireoide/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Disruptores Endócrinos/toxicidade , Tireotropina , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo
5.
J Toxicol Sci ; 45(8): 435-447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32741896

RESUMO

The imbalance of testosterone to estradiol ratio has been related to the development of prostate diseases. Although rat models of prostate diseases induced by endocrine-disrupting chemicals (EDCs) and/or hormone exposure are commonly used to analyze gene expression profiles in the prostate, most studies utilize a single endpoint. In this study, microarray analysis was used for gene expression profiling in rat prostate tissue after exposure to EDCs and sex hormones over multiple time points (prepubertal through adulthood). We used dorsolateral prostate tissues from Sprague-Dawley rats (male offspring) and postnatally administered estradiol benzoate (EB) on postnatal days (PNDs) 1, 3, and 5, followed by treatment with additional hormones [estradiol (E) and testosterone (T)] on PNDs 90-200, as described by Ho et al. Microarray analysis was performed for gene expression profiling in the dorsolateral prostate, and the results were validated via qRT-PCR. The genes in cytokine-cytokine receptor interaction, cell adhesion molecules, and chemokines were upregulated in the EB+T+E group on PNDs 145 and 200. Moreover, early-stage downregulation of anti-inflammatory gene: bone morphogenetic protein 7 gene was observed. These findings suggest that exposure to EB, T, and E activates multiple pathways and simultaneously downregulates anti-inflammatory genes. Interestingly, these genes are reportedly expressed in prostate cancer tissues/cell lines. Further studies are required to elucidate the mechanism, including analyses using human prostate tissues.


Assuntos
Disruptores Endócrinos/toxicidade , Estradiol/análogos & derivados , Estradiol/toxicidade , Perfilação da Expressão Gênica/métodos , Expressão Gênica , Próstata/metabolismo , Puberdade , Testosterona/toxicidade , Transcriptoma , Fatores Etários , Animais , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Disruptores Endócrinos/efeitos adversos , Estradiol/efeitos adversos , Inflamação/genética , Masculino , Análise em Microsséries , Ratos Sprague-Dawley , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Testosterona/efeitos adversos
6.
PLoS One ; 15(8): e0236104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776939

RESUMO

There is an increasing emphasis on effects-based monitoring to document responses associated with exposure to complex mixtures of chemicals, climate change, pathogens, parasites and other environmental stressors in fish populations. For decades aquatic monitoring programs have included the collection of tissues preserved for microscopic pathology. Consequently, formalin-fixed, paraffin-embedded (FFPE) tissue can be an important reservoir of nucleic acids as technologies emerge that utilize molecular endpoints. Despite the cross-linking effects of formalin, its impact on nucleic acid quality and concentration, amplification, and sequencing are not well described. While fresh-frozen tissue is optimal for working with nucleic acids, FFPE samples have been shown to be conducive for molecular studies. Laser capture microdissection (LCM) is one technology which allows for collection of specific regions or cell populations from fresh or preserved specimens with pathological alterations, pathogens, or parasites. In this study, smallmouth bass (Micropterus dolomieu) liver was preserved in three different fixatives, including 10% neutral buffered formalin (NBF), Z-Fix® (ZF), and PAXgene® (PG) for four time periods (24 hr, 48 hr, seven days, and 14 days). Controls consisted of pieces of liver preserved in RNALater® or 95% ethanol. Smallmouth bass were chosen as they are an economically important sportfish and have been utilized as indicators of exposure to endocrine disruptors and other environmental stressors. Small liver sections were cut out with laser microdissection and DNA and RNA were purified and analyzed for nucleic acid concentration and quality. Sanger sequencing and the NanoString nCounter® technology were used to assess the suitability of these samples in downstream molecular techniques. The results revealed that of the formalin fixatives, NBF samples fixed for 24 and 48 hr were superior to ZF samples for both Sanger sequencing and the Nanostring nCounter®. The non-formalin PAXgene® samples were equally successful and they showed greater stability in nucleic acid quality and concentration over longer fixation times. This study demonstrated that small quantities of preserved tissue from smallmouth bass can be utilized in downstream molecular techniques; however, future studies will need to optimize the methods presented here for different tissue types, fish species, and pathological conditions.


Assuntos
Bass/genética , DNA/efeitos dos fármacos , Monitoramento Ambiental/métodos , Fixadores/efeitos adversos , RNA/efeitos dos fármacos , Animais , Clivagem do DNA/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Formaldeído/efeitos adversos , Perfilação da Expressão Gênica/métodos , Fígado/efeitos dos fármacos , Fígado/patologia , Microdissecção , Desnaturação de Ácido Nucleico/efeitos dos fármacos , RNA/isolamento & purificação , Estabilidade de RNA/efeitos dos fármacos , Análise de Sequência de DNA , Fatores de Tempo , Fixação de Tecidos/métodos , West Virginia
7.
Ecotoxicol Environ Saf ; 202: 110944, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800225

RESUMO

Bisphenol A (BPA), a weak estrogenic endocrine disruptor and a well-known plasticizer, has the potential to perturb diverse physiological functions; however, its impact on immune and metabolic function in aquatic vertebrates is relatively less understood. The present study aims to investigate the impact of BPA on hepatotoxicity, metabolic and immune parameters vis-à-vis estrogen receptor expression modulation in a freshwater teleost, Labeo bata (Cyprinidae, Cypriniformes). The 96-h median lethal concentration of BPA in L. bata has been determined as 4.79 mg/L. Our data demonstrate that congruent with induction of plasma vitellogenin (VTG), chronic exposure to sub-lethal BPA (2 and 4 µM/L) attenuates erythrocyte count, hemoglobin concentration, packed cell volume, mean corpuscular hemoglobin, but not leukocyte number. Further, a significant increase in MDA, concomitant with diminished catalase and heightened GST activity corroborates well with hepatic dystrophic changes, appearance of fatty liver (macrovesicular steatosis) and elevated serum lipids (triglyceride, cholesterol, LDL, VLDL) in BPA-treated groups. Interestingly, a differential regulation of estrogen receptor (ER) subtypes at transcript and protein level signifies negative influence of BPA on hepatic ERα/ERß homeostasis in this species. While at a lower dose it promotes Akt phosphorylation (activation), BPA at the higher dose attenuates ERK1/2 phosphorylation (activation), suggesting potential alteration in insulin sensitivity. Importantly, dose-dependent decrease in hepatic TNF-α, IL-1ß, iNOS (NOS2) expression and nitric oxide (NO) level corresponds well with progressive decline in p-NF-κB, p-p38 MAPK, albeit with differential sensitivity, in BPA-exposed groups. Collectively, BPA exposure has wide-spread negative influence on hematological, biochemical and hepatic events in this species.


Assuntos
Compostos Benzidrílicos/toxicidade , Cyprinidae/metabolismo , Disruptores Endócrinos/toxicidade , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Receptores Estrogênicos/genética , Animais , Cyprinidae/imunologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Água Doce/química , Expressão Gênica/efeitos dos fármacos , Homeostase , Inflamação , Fígado/imunologia , Fígado/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Vitelogeninas/metabolismo
8.
Ecotoxicol Environ Saf ; 205: 111154, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810643

RESUMO

The study focused on the toxicological effect of Di-n-butyl phthalate (DBP) on the expression of Phosphorylated signal transducer and activator of transcription 1 (pSTAT1) -regulated Forkhead box protein M1 (FoxM1), which might provide a new understanding of gestational diabetes mellitus (GDM) development and a potential target for treatment. Streptozotocin (STZ) (40 mg/kg) was introduced in maternal rats by intraperitoneal injection on gestation day 0 (GD 0) in the STZ and STZ + DBP groups. DBP was introduced in maternal rats by oral feeding in the STZ + DBP group over the following 3 days (750 mg/kg/day). The changes in fasting blood glucose level in rats were detected on GD 1 and GD 5. The insulin levels in maternal rats and PIBCs were measured on GD 18. The Oral Glucose Tolerance Test (OGTT) test was performed on GD 18 to check the stability of the GDM model. The primary islet ß cells (PIBCs) were established for in vitro experiments. We examined the FoxM1 and pSTAT1 expression in pancreas by immunohistochemistry. Real-time PCR and Western blot were used to detect the pSTAR1 and FoxM1 protein and mRNA gene expression levels in PIBCs. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis was used to test the viability and apoptosis of cells. The results showed that the STZ + DBP group had higher glucose and lower insulin secretion levels than the other groups by both fasting test and OGTT. FoxM1 was significantly suppressed while pSTAT1 was highly expressed after DBP exposure. FoxM1 could be regulated by pSTAT1. DBP can influence the progression of GDM through its toxicological effect, which significantly increases the expression of pSTAT1 and suppresses FoxM1, causing a decline in ß cell viability.


Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Gestacional/induzido quimicamente , Dibutilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Proteína Forkhead Box M1/metabolismo , Exposição Materna/efeitos adversos , Fator de Transcrição STAT1/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Gestacional/metabolismo , Feminino , Proteína Forkhead Box M1/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Fosforilação , Gravidez , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT1/genética , Transdução de Sinais
9.
Ecotoxicol Environ Saf ; 205: 111176, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32846301

RESUMO

The effects of 17α-ethinylestradiol (EE2) on sex ratio, gonopodium morphology, and gonadal histology of C. decemmaculatus were assessed by a full-lifecycle exposure experiment. Newborn fish were waterborne exposed to 30, 100, and 300 ng EE2/L for 90 d, using 50 fish per treatment. Additionally, in December of 2016, a field survey was conducted on a C. decemmaculatus population inhabiting the Girado Creek downstream of the Chascomus city wastewater effluent discharge. After 90 d of exposure, EE2 was able to histologically skew the sex ratio toward females and inhibit the full gonopodium development since the lowest tested concentration (LOEC = 30 ng/L). At higher concentrations, EE2 was toxic, inducing mortality in a concentration-dependent fashion (90 d-LC50 = 109.9 ng/L) and altering the gonadal histoarchitecture, causing neither testes nor ovaries discernible histologically (LOEC = 100 ng/L). In addition, a novel response, perianal hyperpigmentation, was discovered been induced by the EE2 exposure in a concentration-dependent fashion (90 d-EC50 = 39.3 ng/L). A higher proportion of females and perianal hyperpigmentation were observed in wild fish collected from the Girado Creek. The major reached conclusions are: i) EE2 induce different effects on the sexual traits of C. decemmaculatus when exposed from early-life or adult stages. ii) The most sensitive effects observed in the laboratory occur in a creek receiving wastewater effluent. iii) The perianal hyperpigmentation comes-up as a promising biomarker of exposure to estrogenic compounds.


Assuntos
Ciprinodontiformes/crescimento & desenvolvimento , Disruptores Endócrinos/toxicidade , Etinilestradiol/toxicidade , Gônadas/efeitos dos fármacos , Hiperpigmentação/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Gônadas/crescimento & desenvolvimento , Gônadas/patologia , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovário/patologia , Fenótipo , Razão de Masculinidade , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testículo/patologia
10.
PLoS One ; 15(8): e0236708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790684

RESUMO

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are a kind of endocrine disruptors, which can enter human body by the inhalation of PAH-containing matter and the ingestion of PAH-containing foodstuffs. Studies showed that PAHs can cross the placental barrier and might cause adverse effects on the fetus. OBJECTIVES: This meta-analysis aimed to estimate the associations between prenatal exposure to PAHs and birth weight. METHODS: Articles published in English until May 8, 2020 and reported the effects of prenatal exposure to PAHs on birth weight were searched in multiple electronic databases including PubMed, the Web of Science, EMBASE and the Cochrane Library. The included studies were divided into three groups in accordance with the measurement of PAHs exposure. Then coefficient was extracted, conversed and synthesized by random-effects meta-analysis. And risk of bias was assessed for each study. RESULTS: A total of 3488 citations were searched and only 11 studies were included finally after double assessment. We found that there were no association between PAH-DNA adducts in cord blood (low/high) (OR: 1.0, 95%CI: 0.97, 1.03), 1-hydroxy pyrene (1-HP) concentration in maternal urine (OR: 1.0, 95%CI: 0.97, 1.03) and prenatal maternal airborne PAHs exposure (OR: 0.97, 95%CI: 0.93, 1.01) and birth weight. However, we observed ethnicity may change the effects of PAHs exposure on birth weight. CONCLUSIONS: There is no significant relationship between prenatal exposure to PAHs and birth weight in our meta-analysis. Further studies are still needed for determining the effects of prenatal PAHs exposure on birth weight.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Exposição Materna , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Atmosféricos/química , Poluentes Atmosféricos/toxicidade , Adutos de DNA/química , Bases de Dados Factuais , Disruptores Endócrinos/química , Feminino , Sangue Fetal/química , Humanos , Razão de Chances , Hidrocarbonetos Policíclicos Aromáticos/química , Gravidez , Pirenos/urina
11.
PLoS One ; 15(8): e0237705, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833973

RESUMO

Polychlorinated biphenyls (PCBs) are environmental pollutants and endocrine disruptors, harmfully affecting reproductive, endocrine, neurological and immunological systems. This broad influence has implications for processes such as wound healing, which is modulated by the immunological response of the body. Conversely, while PCBs can be linked to diminished wound healing, outside of PCB pollution systems, exercise has been shown to accelerate wound healing. However, the potential for moderate intensity exercise to modulate or offset the harmful effects of a toxin like PCB are yet unknown. A key aim of the present study was to examine how PCB exposure at different doses (0, 100, 500, 1000 ppm i.p.) altered wound healing in exercised versus non-exercised subgroups of mice. We examined PCB effects on immune function in more depth by analyzing the concentrations of cytokines, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) in these wounds inflicted by punch biopsy. Mice were euthanized at Day 3 or Day 5 after PCB injection (n = 3-6) and skin excised from the wound area was homogenized and analyzed for cytokine content. Results revealed that wound healing was not signficantly impacted by either PCB exposure or exercise, but there were patterns of delays in healing that depended on PCB dose. Changes in cytokines were also observed and depended on PCB dose and exercise experience. For example, IL-1ß concentrations in Day 5 mice without PCB administration were 33% less in exercised mice than mice not exercised. However, IL-1ß concentrations in Day 3 mice administered 100 ppm were 130% greater in exercised mice than not exercisedmice. Changes in the other measured cytokines varied with mainly depressions at lesser PCB doses and elevations at higher doses. Exercise had diverse effects on cytokine levels, but increased cytokine levels in the two greater doses. Explanations for these diverse effects include the use of young animals with more rapid wound healing rates less affected by toxin exposure, as well as PCB-mediated compensatory effects at specific doses which could actually enhance immune function. Future work should examine these interactions in more detail across a developmental time span. Understanding how manipulating the effects of exposure to environemntal contaminants using behavioral modification could be very useful in certain high risk populations or exposed individuals.


Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Condicionamento Físico Animal/fisiologia , Bifenilos Policlorados/toxicidade , Cicatrização/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Pele/imunologia , Pele/lesões , Pele/metabolismo , Cicatrização/efeitos dos fármacos
12.
Ecotoxicol Environ Saf ; 204: 111068, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32745784

RESUMO

Herein, eight common endocrine disrupting chemicals (EDCs) were exposed to zebrafish (Danio rerio) to investigate the relationship between different EDCs and their activated estrogen receptors. Under acute exposure, we identified five major malformation types whose incidence and deformity modes differed among EDCs. Luciferase analysis divided the EDC receptors into four categories: (i) triclosan (TCS), 17ß-estradiol (E2) and estriol (E3) mainly activated GPER expression; (ii) bisphenol A (BPA), p-(tert-octyl) phenol (POP), 17α-ethynylestradiol (EE2), E2 and E3 activated ERß expression; (iii) E2 and E3 acted on both GPER and ERß; and (iv) estrone (E1) and 9,9-bis(4-hydroxyphenyl)fluorene (BHPF) had little effect on the two receptors. In vivo immunofluorescence experiments on 96-hpf larvae provided evidence that TCS and POP acted on GPER and ERß, respectively, while E2 acted on the two receptors simultaneously. Luciferase activities in the promoter regions of gper (-986 to -488) and erß (-1998 to -1496) were higher than those in other regions, identifying these key regions as targets for transcription activity. TCS promoted GPER expression by acting on the JUND transcription factor, while POP promoted ERß expression by activating the Foxl1 transcription factor. In contrast, E2 mainly regulated transcription of GPER and ERß by Arid3a. These findings provide compelling evidence that different EDCs possess varying estrogen receptors, leading to differential regulatory pathways and abnormality symptoms. These results offer an experimental strategy and fundamental information to assess the molecular mechanisms of EDC-induced estrogen effects.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Receptor beta de Estrogênio/metabolismo , Fenóis/toxicidade , Receptores Acoplados a Proteínas-G/metabolismo , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Compostos Benzidrílicos/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Fenóis/metabolismo , Poluentes Químicos da Água/metabolismo
13.
Sci Total Environ ; 746: 141041, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768778

RESUMO

Extensive use of endocrine disruptor compounds (EDCs) and their release through various pathways into the environment are emerging environmental concerns. In this context, H2O2 and chlorine UV-based treatments were carried out to evaluate their efficiency in the removal of the bisphenol A (BPA), 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2) at 100 µg L-1 from ultrapure water and from wastewater treatment plants (WWTP). Photolysis was performed under different irradiation sources, i.e. UVC and UVA. The effect of H2O2 (3 and 30 mg·L-1), free chlorine concentrations (1 and 2 mg·L-1) and pH (5, 7 and 9) were also investigated. Toxicity (Raphidocelis subcapitata) and estrogenic activity (yeast estrogen screen - YES assay) were assessed during the processes. Compound removal at optimal operating parameters reached 100% after 15 and 2 min for UVC/H2O2 (pH 9 and 3 mg L-1 of H2O2), and UVC/Cl (pH 9 and 2 mg L-1 of chlorine), respectively. Total organic carbon (TOC) removal achieved 37% and 45% for the H2O2 and Cl-UV based process, respectively. The in vitro YES assay indicated that the formed by-products were non-estrogenic compounds, while the toxicity evaluation revealed high cell growth inhibition due to UVC/Cl byproducts. During the UV-based processes, 30 transformation products (TPs) were identified, in which three new chlorinated TPs from E2 and EE2 may be responsible for toxicity effects. EDC degradation by UV/Cl is faster than by UV/H2O2, although chlorinated toxic byproducts were also formed during the UV/Cl process.


Assuntos
Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Cloro , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Oxirredução , Raios Ultravioleta , Águas Residuárias
14.
J Toxicol Sci ; 45(7): 373-390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612006

RESUMO

DEHP (di-2-ethylhexyl phthalate), an environmental endocrine disruptor, is widely used in industrial products, particularly as plasticizers and softeners which could disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis. Rosmarinic acid (RA) possesses potential antioxidant and anti-inflammatory capacities in disease models. Nevertheless, evidence on the association between DEHP-induced thyroid dysfunction and inflammation, as well as the molecular mechanism underlying the protective effects of RA-mitigated DEHP-induced thyroid injury remains inconclusive. Male Sprague Dawley (SD) rats were intragastrically administered DEHP (150 mg/kg, 300 mg/kg, 600 mg/kg) once a day for 90 consecutive days. Also, FRTL-5 cells were treated with a wide range of DEHP concentrations (10-8, 10-7, 10-6, 10-5, 10-4, 10-3, 10-2 M) for 24 hr. Subsequently, RA (50 µM) was administered for 24 hr before 10-4 M DEHP challenge. We found that DEHP induced thyroid damage and inflammatory infiltration in vivo. In addition, we showed that DEHP triggered inflammatory cell death, which is mediated by multiple inflammasomes. Moreover, RA, pyroptosis inhibitor (Ac-YVAD-cmk) and antioxidant inhibitor (NAC) treatment significantly alleviated DEHP-induced thyrocyte death, suppressing pro-inflammatory cytokine production, inhibiting multiple inflammasomes activation and attenuating thyrocyte death, respectively. Collectively, our results reveal that a critical role of inflammasomes activation in DEHP-induced thyroid injury, and suggest that RA confers protection against DEHP-induced thyroid inflammation, and facilitating control of the effects of DEHP after given pyroptosis inhibitor or antioxidant inhibitor. These results indicate that it should be possible to provide novel insights into toxicologically and pharmacologically targeting this molecule to DEHP-induced inflammation.


Assuntos
Anti-Inflamatórios , Antioxidantes , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Depsídeos/farmacologia , Depsídeos/uso terapêutico , Dietilexilftalato/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Inflamassomos/metabolismo , Fitoterapia , Animais , Boraginaceae , Morte Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Dietilexilftalato/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Disruptores Endócrinos/toxicidade , Hipotireoidismo/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Ratos Sprague-Dawley , Células Epiteliais da Tireoide/efeitos dos fármacos
15.
Chemosphere ; 259: 127221, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32615454

RESUMO

Due to its unique properties, graphene oxide (GO) has potential for biomedical and electronic applications, however environmental contamination including aquatic ecosystem is inevitable. Moreover, potential risks of GO in aquatic life are inadequately explored. Present study was designed to evaluate GO as an endocrine disrupting chemical (EDC) using the model Japanese medaka (Oryzias latipes). GO was injected intraperitoneally (25-200 µg/g) once to breeding pairs and continued pair breeding an additional 21 days. Eggs laid were analyzed for fecundity and the fertilized eggs were evaluated for developmental abnormalities including hatching. Histopathological evaluation of gonads, liver, and kidneys was made 21 days post-injection. LD50 was found to be sex-dependent. Fecundity tended to reduce in a dose-dependent manner during early post-injection days; however, the overall evaluation showed no significant difference. The hatchability of embryos was reduced significantly in the 200 µg/g group; edema (yolk and cardiovascular) and embryo-mortality remained unaltered. Histopathological assessment identified black particles, probably agglomerated GO, in the gonads of GO-treated fish. However, folliculogenesis in stromal compartments of ovary and the composition of germinal elements in testis remained almost unaltered. Moreover, granulosa and Leydig cells morphology did not indicate any significant EDC-related effects. Although liver and kidney histopathology did not show GO as an EDC, some GO-treated fish accumulated proteinaceous fluid in hepatic vessels and induced hyperplasia in interstitial lymphoid cells (HIL) located in kidneys. GO agglomerated in medaka gonads after 21-days post-injection. However, gonad histopathology including granulosa and Leydig cells alterations were associated with GO toxicity rather than EDC effects.


Assuntos
Grafite/toxicidade , Oryzias/fisiologia , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Ecossistema , Disruptores Endócrinos/toxicidade , Feminino , Fertilidade/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Ovário/efeitos dos fármacos , Testículo/efeitos dos fármacos
16.
Environ Sci Pollut Res Int ; 27(32): 40882-40892, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32681327

RESUMO

Phthalates and bisphenols are two typical classes of endocrine-disrupting chemicals (EDCs) which cause endocrine disorder in humans and animals. Phthalates and bisphenols are suggested to be associated with thyroid dysfunction. However, the effects of combined exposure and the detailed mechanisms are yet poorly understood. We investigated the combined effects of di (2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) on thyroid function during puberty. Female Sprague Dawley rats were gavaged from postnatal 28 to 70 days with a single or combined exposure of DEHP (0, 150, and 750 mg/kg/day) and BPA (0, 20, and 100 mg/kg/day) according to a 3 × 3 factorial design. The thyroid weights reduced after combined exposure to the highest dose of DEHP and BPA, which noted their adverse effects on thyroid. Additionally, DEHP could increase the number of follicular epithelial cells in thyroid. Both DEHP and in combination with BPA could disturb the levels of thyroid hormones in serum, such as TT3 and TT4. Meanwhile, the possible mechanism was also discussed in the present study. DEHP treatment induced a significant increase of phosphorylation of cAMP-response element binding protein (Creb) via estrogen receptor α (Esr1), while the upregulation was nullified by the concomitant presence of BPA. In conclusion, the complex action of DEHP/BPA mixture may disturb the thyroid hormone homeostasis, which ultimately would affect the development of thyroid during puberty.


Assuntos
Dietilexilftalato , Disruptores Endócrinos , Animais , Compostos Benzidrílicos/toxicidade , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Homeostase , Humanos , Fenóis , Ácidos Ftálicos , Ratos , Ratos Sprague-Dawley , Hormônios Tireóideos
17.
Toxicol Lett ; 332: 14-19, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32619634

RESUMO

Based on human estrogen receptor α ligand binding domain (hERα-LBD) as recognition element, a fluorescence polarization assay was developed for the determination of bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and their derivatives. Fluorescence polarization assay showed that BADGE, BFDGE and their derivatives exhibited dose-dependent binding to the receptor protein. The results of reporter gene assay indicated that all the tested bisphenol diglycidyl ethers show no agonistic activities, but some of them exhibit anti-estrogenic activities toward ERα. All the tested bisphenol diglycidyl ethers fitted into the hydrophobic binding pocket and adopted the conformation that resembled 4-hydroxytamoxifen, a selective antagonist of ERα. Quantitative structure-activity relationship analysis showed that the binding potencies of bisphenol diglycidyl ethers with hERα-LBD might be structure-dependent. This work may provide insight into the in silico screening of ER ligands from unsuspected chemicals.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Compostos de Epóxi/toxicidade , Receptor alfa de Estrogênio/efeitos dos fármacos , Simulação por Computador , Relação Dose-Resposta a Droga , Antagonistas de Estrogênios/farmacologia , Imunoensaio de Fluorescência por Polarização , Genes Reporter , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Ligação Proteica , Relação Estrutura-Atividade
18.
Aquat Toxicol ; 226: 105557, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32645606

RESUMO

Extensive studies have shown that estrogenic endocrine-disrupting chemicals (EDCs) can disrupt testis differentiation and even cause feminization in vertebrates. However, little is known about the mechanisms by which estrogenic EDCs disrupt testis differentiation. Here, we employed Xenopus laevis, a model amphibian species sensitive to estrogenic EDCs, to explore the molecular and cellular events by which 17ß-estradiol (E2) disrupts testis differentiation and causes feminization. Following waterborne exposure to E2 from stage 45/46, genetically male X. laevis were confirmed to undergo testis differentiation inhibition and ovary differentiation activation at stages 52 and 53, ultimately displaying gonadal feminization at stage 66. Using a time-course RNA sequencing approach, we then identified thousands of differentially expressed transcripts (DETs) in genetically male gonad-mesonephros complexes at stages 48, 50 and 52 (the window for testis differentiation) between E2 treatment and the control. Enrichment analysis suggests alterations in cell proliferation, extracellular matrix, and cell motility following E2 exposure. Further verification by multiple methods demonstrated that E2 inhibited cell proliferation, disrupted extracellular matrix, and altered cell motility in the genetically male gonads compared with controls, implying that these events together contributed to testis differentiation disruptions and feminization in X. laevis. This study for the first time uncovered some of the early molecular and cellular events by which estrogen disrupts testicular differentiation and causes feminization in X. laevis. These new findings improve our understanding of the mechanisms by which estrogenic EDCs disrupt testicular differentiation in vertebrates.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Feminização , Testículo/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Feminização/induzido quimicamente , Feminização/genética , Perfilação da Expressão Gênica , Humanos , Larva/efeitos dos fármacos , Larva/genética , Masculino , Ovário/efeitos dos fármacos , Xenopus laevis
19.
Aquat Toxicol ; 226: 105580, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32712368

RESUMO

Bisphenol A (BPA), a well-known estrogenic endocrine disruptor, is ubiquitously present in the environment, possessing the potential to interfere with the reproductive endocrine system in male mammals. However, there are limited studies on the reproductive toxicity in male aquatic animals associated with epigenetic modifications. In order to evaluate the potential effects of BPA on reproduction and better understand the underlying mechanism, adult male rare minnow (Gobiocypris rarus) were exposed to 15 µg L-1 BPA over a period of 63 d. Results showed that BPA induced congestion of blood vessels and infiltration of inflammatory cells after 21 d exposure, and decreased sperm fertilization after 63 d exposure. The genome DNA methylation levels were significantly increased throughout the treatment, and a strong positive stain were found in the spermatocyte, spermatid and sperm. The H3K4me3 level in all types of germ cell were increased by 21 d exposure while decreased following 63 d exposure. The positive stain of H3K9me3 was decreased in sperms while increased in spermatids by 21 d exposure. In addition, the H3K9me3 level was significantly increased after 63 d exposure, and a strong positive stain were found in spermatocytes, spermatids, and sperms. Our result also revealed that the transcripts of DNA methyltransferase genes (dnmt1 and dnmt3-8) and histone methyltransferase genes (mll2-5, setdb1-2 and ezh2) were also markedly changed under BPA exposure for 21-63 d. These findings indicated that BPA had toxicity in male reproductive, and DNA/histone methylation might play a vital role in the regulation of BPA-triggered the decreased of sperm quality.


Assuntos
Compostos Benzidrílicos/toxicidade , Cyprinidae/metabolismo , Metilação de DNA/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Histonas/metabolismo , Fenóis/toxicidade , Espermatozoides/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , DNA/metabolismo , Feminino , Humanos , Masculino , Análise do Sêmen , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos
20.
Bull Environ Contam Toxicol ; 105(2): 218-223, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32591851

RESUMO

The adverse effects of endocrine disruptors (EDs) on aquatic wildlife and human health represent a current issue of high public concern. Substantial knowledge of the level of estrogenic EDs in fish has accumulated from field surveys. For this purpose, a survey of wild brown trout (Salmo trutta trutta) was carried out to assess the incidence of EDs in the feral fish population living in the Liri river (Abruzzi, Italy). The results of this study show that this aquatic environment possesses an estrogenic potency that triggered the increase of vitellogenin levels in both female and male trouts. Fish exposed to different pesticides and urban waste in downstream river showed higher vitellogenin levels in comparison to the headwater site. Furthermore, some trouts coming from the downstream reported the presence of several pesticides and fungicides, some of these banned several years ago.


Assuntos
Monitoramento Biológico/métodos , Disruptores Endócrinos/toxicidade , Rios/química , Truta/metabolismo , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Disruptores Endócrinos/análise , Feminino , Itália , Masculino , Poluentes Químicos da Água/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA